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Efficacy and Safety of GSK1358820 in Subjects With Overactive Bladder

Primary Purpose

Urinary Bladder, Overactive

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

GSK1358820

Placebo

Antibiotic therapy

Bladder diary

King's Health Questionnaire (KHQ)

Overactive Bladder Symptom Score (OABSS)

Treatment Benefit Scale (TBS)

About this trial

This is an interventional treatment trial for Urinary Bladder, Overactive focused on measuring Overactive bladder, Botulinum toxin type A, Urinary incontinence

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Aged >=20 years at the time of signing the informed consent.
Subject has symptoms of OAB (frequency and urgency) with urinary incontinence for a period of at least 6 months immediately prior to screening, determined by documented subject history.
Subject has not been adequately managed with one or more medications (that is, anticholinergics or beta-3 adrenergic receptor agonist) for treatment of their OAB symptom. 'Not adequately managed' is defined as: An inadequate response after at least a 4-week period of OAB medication(s) on an approved optimized dose(s), that is, subject is still incontinent despite medication(s) for OAB; or limiting side effects (that is, condition that subject reduced dosage or discontinued the medication due to side effect after at least a 2-week period of OAB medication(s) on an approved optimized dose(s)).
Subject who experiences all of the following, in the 3-day subject bladder diary completed during the screening phase:
1. >= 3 episodes of urinary urgency incontinence, with no more than one urgency incontinence-free day
2. urinary frequency (defined as an average of >= 8 micturitions [toilet voids] per day, that is, a total of >= 24 micturitions)
Subject is willing to use clean intermittent catheterization (CIC) to drain urine if it is determined to be necessary by the investigator (or subinvestigator).
Body weight >=40 kilograms (kg) at screening.
Males or females:
1. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until the study exit:
  - Vasectomy with documentation of azoospermia.
  - Male condom plus partner use of one of the contraceptive options below: Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; or oral contraceptive, either combined or progestogen alone.
  These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
2. Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine or serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:
  • Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.
  Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
  • Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until the study exit. This list of highly effective methods (approved in Japan) is provided below, and it does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.
  These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
Subject has given signed informed consent, including compliance with the requirements and restrictions listed in the consent form and in this protocol (example, using the toilet without assistance, complete bladder diaries and questionnaires, is able to collect volume voided per micturition measurements over a 24-hour period, and attend all study visits in the opinion of the investigator (or subinvestigator).

Exclusion Criteria:

Subject has symptoms of OAB due to any known neurological reason (example, spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer's disease, Parkinson's disease, etc.)
Subject has a predominance of stress incontinence determined by subject history.
Subject has a history or evidence of any diseases, functional abnormalities or bladder surgery, other than OAB, that may have affected bladder function including but not limited to:
1. Bladder stones (including bladder stone surgery) within 6 months prior to screening or confirmed occurrence of bladder stones at the screening phase
2. Surgery (including minimally invasive surgery) within 1 year of screening for stress incontinence or pelvic organ prolapse
3. Current use of an electrostimulation/neuromodulation device for treatment of urinary incontinence. Note: Use of any implantable device is prohibited within 4 weeks prior to initiation of screening phase and throughout the study period. Use of any external device is prohibited within 7 days prior to the start of the screening phase
4. History of interstitial cystitis, in the opinion of the investigator (or subinvestigator)
5. Past or current evidence of hematuria due to urological/renal pathology or uninvestigated hematuria. Subjects with investigated hematuria may enter the study if urological/renal pathology has been ruled out to the satisfaction by the investigator (or subinvestigator).
6. Past or current history of bladder cancer or other urothelial malignancy, positive result of urine cytology or uninvestigated suspicious urine cytology results at the Screening phase. Suspicious urine cytology abnormalities require that bladder cancer or other urothelial malignancy has been ruled out to the satisfaction of the investigator according to local site practice.
7. An active genital infection, other than genital warts, either concurrently or within 4 weeks prior to Screening
8. Male with previous or current diagnosis of prostate cancer or a prostate specific antigen (PSA) level of >10 nanograms (ng)/mL at Screening. Subjects with a PSA level of >= 4 ng/mL but <= 10 ng/mL must have prostate cancer ruled out to the satisfaction of the investigator (or subinvestigator) according to local site practice.
9. Evidence of urethral and/or bladder outlet obstruction, in the opinion of the investigator (or subinvestigator)
Subject has a history of 2 or more urinary tract infections (UTIs) within 6 months of initiation of Treatment phase 1 (Week 0) or current administration of prophylactic antibiotics to prevent chronic UTIs
Subject has a positive urine dipstick reagent strip test at initiation of Treatment phase 1 (Week 0) for nitrites or leukocyte esterase, or who are considered by the investigator (or subinvestigator) to have UTI.
Subject has a serum creatinine level >2 times the upper limit of normal (ULN) at screening.
Alanine aminotransferase (ALT) > 2xULN; and bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
Subject has current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Notes:
1. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis
2. Chronic stable hepatitis B and C (example, presence of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody [HCVAb] test result within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria
QT corrected (QTc) > 450 milliseconds (msec) or QTc > 480 msec in subjects with Bundle Branch Block from the result of electrocardiogram (ECG) at screening. Notes:
1. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read
2. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial
Subject has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diathesis.
Subject received anticholinergic, beta-3 adrenergic receptor agonist or any other medications or therapies to treat symptoms of OAB, including nocturia, within 7 days prior to the start of the screening phase.
Subject has been treated with any intravesical pharmacologic agent (example, capsaicin, resiniferatoxin) for OAB symptoms within 12 months prior to initiation of Treatment phase 1 (Week 0).
Subject has previous or current use of botulinum toxin therapy of any serotype for the treatment of any urological condition.
Subject has previous use within 12 weeks prior to initiation of Treatment phase 1 (Week 0) or current use of botulinum toxin therapy of any serotype for any non-urological condition or beauty care.
Subject has been immunized for botulinum toxin of any serotype.
Subject cannot withhold any antiplatelet or anticoagulant therapy or medications with anticoagulative effects for 3 days prior to initiation of Treatment phase 1 (Week 0). Some medications may need to be withheld for >3 days, per clinical judgment of the investigator (or subinvestigator).
Subject has not initiated appropriate antibiotic medication 1 to 3 days prior to the initiation of Treatment phase 1 (Week 0).
Subject uses CIC or indwelling catheter to manage their urinary incontinence.
Subject has a history of sensitivity to any of the study medications, medications used in the study (including anesthesia), or their components or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
Subject has any medical condition that may put them at increased risk with exposure to GSK1358820 including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis.
Females who are pregnant, nursing or planning a pregnancy during the study.
Subject has a PVR urine volume of >100 mL at screening phase. The PVR measurement can be repeated once; the subject is to be excluded if the repeated measure is above 100 mL.
Subject has had urinary retention or an elevated PVR urine volume within 6 months of screening that has been treated with an intervention (such as catheterization). Voiding difficulties as a result of surgical procedures that resolved within 24 hours are not exclusionary.
Subject has a 24-hour total volume of urine voided >3000 mL of urine collected over 24 consecutive hours during the 3-day bladder diary collection period in the Screening phase.
Subject is currently participating in or has previously participated in another therapeutic study within 30 days prior to the start of the Screening phase.
Subject has any condition or situation which, in the investigator's (or subinvestigator's) opinion, puts the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GSK1358820 Injection 100 U

Placebo Injection

Arm Description

Initially, subjects will receive a single (double-blind) treatment with GSK1358820 (20 injections of 0.5 mL each) into the detrusor muscle of the bladder, using cystoscopy, and under local anesthesia. If the criteria for re-treatment are met between 12 and 36 weeks after the first treatment, subjects will receive a second treatment with GSK1358820 (open-label). A third treatment with GSK1358820 (open-label) may be given until 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment. Subjects will receive prophylactic antibiotic therapy beginning up to 3 days prior to treatment and continuing up to 3 days following treatment.

Initially, subjects will receive a single (double-blind) treatment with Placebo (20 injections of 0.5 mL each) into the detrusor muscle of the bladder, using cystoscopy, and under local anesthesia. If the criteria for re-treatment are met between 12 and 36 weeks after the first treatment, subjects will receive a second treatment, this time with open-label GSK1358820. A third treatment with open-label GSK1358820 may be given until 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment. Subjects will receive prophylactic antibiotic therapy beginning up to 3 days prior to treatment and continuing up to 3 days following treatment.

Outcomes

Primary Outcome Measures

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in the Daily Average Number of Urinary Incontinence Episodes at Week 12 After the First Treatment

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated using formula; number of "Yes" response to the diary question of accidental urinary leakage divided by number of valid diary days in the visit. Baseline is the latest pre-dose 3- day diary assessment which has at least one valid diary day. Change from Baseline is any visit value minus Baseline value. Adjusted mean and standard error of adjusted mean has been reported.

Secondary Outcome Measures

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in the Average Volume Voided Per Micturition at Week 12 After the First Treatment

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value. Adjusted mean and standard error of adjusted mean has been reported.

Treatment Phase 1 (Treatment Cycle 1): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value. FAS2 Population comprised all randomized participants who had at least 1 post-2nd treatment efficacy assessment after 2nd treatment.

Treatment Phase 2 (Treatment Cycle 3): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value. FAS3 Population comprised of all randomized participants who had at least 1 post-3rd treatment efficacy assessment after 3rd treatment.

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Voids

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Voids

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Voids

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Voids

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Voids

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Voids

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Average Volume Voided Per Micturition

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Average Volume Voided Per Micturition

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Average Volume Voided Per Micturition

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Average Volume Voided Per Micturition

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Average Volume Voided Per Micturition

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Average Volume Voided Per Micturition

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Urgency Episodes

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Urgency Episodes

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Urgency Episodes

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Nocturia Episodes

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Nocturia Episodes

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Nocturia Episodes

Treatment Phase 1 (Treatment Cycle 1): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 2): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 2 (Treatment Cycle 3): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Severe Urgency Episodes

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency) to '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe urgency episodes was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Severe Urgency Episodes

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Severe Urgency Episodes

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Maximum Urgency Intensity

The daily average number of urgency episodes categorized by each urgency intensity as no urgency (None), mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency) to '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. "Maximum" was defined as the maximum urgency intensity within 3-day period (but only for valid diary day) in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 2 (Treatment Cycle 2): Number of Participants With Maximum Urgency Intensity

Treatment Phase 2 (Treatment Cycle 3): Number of Participants With Maximum Urgency Intensity

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Urgency intensity was determined using a 4-point scale ranging from 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe) as part of the bladder diary, during the 3-day diary collection period. "Maximum" was defined as the maximum urgency intensity within 3-day period (but only for valid diary day) in the visit. Results have been presented for improvement (3 point, 2 point, 1 point improvement and no change) as well as for worsening (1 point, 2 point, 3 point worsening) of urgency intensity. Maximum possible scale range is 0 to 3. 3 point improvement means change in intensity from severe to none. 3 point worsening means change in intensity from none to severe. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 2 (Treatment Cycle 2): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Treatment Phase 2 (Treatment Cycle 3): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants Attaining 100 Percent (%), >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated using formula; number of "Yes" response to the diary question of "Did you have accidental urinary leakage?" divided by number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Treatment Phase 1 (Treatment Cycle 1): Time to Qualification for Retreatment

Participants were considered for re-treatment beginning at the Week 12 visit following the initial treatment or the Week 12 visit following any re-treatment. Qualification criteria was; participants must have initiated request for re-treatment, participants experienced >=2 episodes of urinary urgency incontinence, with no more than one urgency incontinence-free day, post-void residual (PVR) urine volume must have been <200 milliliter; investigator deemed re-treatment appropriate. Time to the participant's first qualification for 2nd treatment from the day of 1st treatment was calculated as the earliest date when participants fulfilled the qualification for retreatment criteria minus the day of first treatment plus 1.

Treatment Phase 1 (Treatment Cycle 1): Time to Request for Retreatment

The time taken by the participants to request re-treatment was reported. Time to the participant's first request for 2nd treatment from the day of 1st treatment was calculated as the earliest date when participants requested retreatment minus the day of first treatment plus 1.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores

KHQ is a 21 item questionnaire, consisting of 9 domains: General health (GH) (1[Very good] to 5[Very poor]), Incontinence impact (Int Imp) (1[Not at all] to 4[A lot]), Role Limitations (RL) (1[Not at all] to 4[A lot]), Physical limitations (PL) (1[Not at all] to 4[A lot]), Social limitations (SL) (0[not applicable] to 4[A lot]), Personal relationships (PR) (0[Not applicable] to 4[A lot]), Emotions (1[Not at all] to 4[Very much]), Sleep/ energy (S/ E) (1[Never] to 4[All the time]) and Severity/Coping (S/ C) (1[Never] to 4[All the time]). Domain score for GH was calculated as score of one item minus 1/4x100; Int Imp: score of one item minus 1/3x100; RL, PL, PR, S/ E: summed scores of 2 items minus 2/6x100; SL, Emotions: summed scores of 3 items minus 3/9x100; S/ C: summed scores of 5 items minus 5/15x100. Baseline is the latest pre-dose assessment with a non-missing value,including those from unscheduled visits. Change from Baseline was any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in KHQ Domain Scores

KHQ is a 21 item questionnaire, consisting of 9 domains: GH (1[Very good] to 5[Very poor]), Int Imp (1[Not at all] to 4[A lot]), RL (1[Not at all] to 4[A lot]), PL (1[Not at all] to 4[A lot]), SL (0[not applicable] to 4[A lot]), PR (0[Not applicable] to 4[A lot]), Emotions (1[Not at all] to 4[Very much]), S/ E (1[Never] to 4[All the time]) and S/ C (1[Never] to 4[All the time]). Domain score for GH was calculated as score of one item minus 1/4x100; Int Imp: score of one item minus 1/3x100; RL, PL, PR, S/ E: summed scores of 2 items minus 2/6x100; SL, Emotions: summed scores of 3 items minus 3/9x100; S/ C: summed scores of 5 items minus 5/15x100. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in KHQ Domain Scores

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants With Positive Response on the Treatment Benefit Scale (TBS)

Treatment benefit of GSK1358820 was assessed with TBS ranging from 1(Greatly improved) to 4 (Worsened). This questionnaire consists of 4 answers to 1 question by considering current condition of participants (urinary problems, urinary incontinence) compared to condition before participants received any study treatment in this trial. Positive treatment response was defined as score of either 1 or 2 (representing 'greatly improved' or 'improved').

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants With Positive Response on the TBS

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants With Positive Response on the TBS

Treatment Phase 1 (Treatment Cycle 1): Changes From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score

Symptoms of frequency, nocturia, urinary urgency, and urge incontinence were assessed. OABSS questionnaire consisted of 4 questions: number of times participants urinate from waking in the morning until sleeping at night, ranging from 0 (<=7 times) to 1 (>=15 times); number of times participants wake up to urinate from sleeping at night until waking in the morning, ranging from 0 (0 times) to 3 (>=3 times); number of times for sudden desire to urinate, ranging from 0 (Not at all) to 5 (5 times a day or more); number of times of urine leakage, ranging from 0 (Not at all) to 5 (5 times a day or more). OABSS total score was calculated as the sum of scores for above 4 questions. The range of total score of OABSS was 0 to 15 with higher score indicating, more severity of symptoms. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2): Changes From Baseline in OABSS Total Score

Treatment Phase 2 (Treatment Cycle 3): Changes From Baseline in OABSS Total Score

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or other situations as per medical or scientific judgment.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With SAEs and Non-SAEs: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With SAEs and Non-SAEs: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With SAEs and Non-SAEs: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With SAEs and Non-SAEs: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressure was measured in seated position after 5 minutes rest for participants at indicated time points. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in SBP and DBP: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in SBP and DBP: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in SBP and DBP: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in SBP and DBP: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Heart Rate

Heart rate was measured in seated position after 5 minutes rest for participants at indicated time points. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Heart Rate: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Heart Rate: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Heart Rate: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Heart Rate: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Temperature

Temperature was measured in seated position after 5 minutes rest for participants at indicated time points. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Temperature: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Temperature: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Temperature: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Temperature: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Blood samples were collected for analysis of following clinical chemistry parameters; Albumin, Alkaline Phosphatase (Alk Phosp), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Direct Bilirubin (Bil), Total Bil, Calcium, Chloride, Creatinine, Glucose, Potassium, Sodium, Total Protein (T Protein), Urea/blood urea nitrogen (BUN) and Uric acid. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g. High to High) or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 percent. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Blood samples were collected for analysis of following clinical chemistry parameters; Albumin, Alk Phosp, ALT, AST, Direct Bil, Total Bil, Calcium, Chloride, Creatinine, Glucose, Potassium, Sodium, T Protein, Urea/BUN and Uric acid. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g. High to High) or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 percent. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Blood samples were collected from participants for analysis of following hematology parameters; Basophils, Eosinophils (Eosino), Hemoglobin (Hb), Hematocrit (Hct), Lymphocytes (Lympho), Monocytes, Neutrophil Bands (N bands), Total Neutrophils (T neutro), Platelet count (PC), Red Blood Cell (RBC) count, and White Blood Cell count (WBC). Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g. High to High) or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 percent. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Blood samples were collected from participants for analysis of following hematology parameters; Basophils, Eosino, Hb, Hct, Lympho, Monocytes, N bands, T neutro, PC, RBC count, and WBC. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g. High to High) or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 percent. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Urine samples were collected for analysis of presence of occult blood and protein in urine using dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of occult blood and protein can be read as negative, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Urinary Tract Infection (UTI)

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 Colony Forming Unit per milliliter (CFU/mL) and leukocyturia with >5 per high power field was noted.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With UTI: Placebo/GSK1358820 100 U

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With UTI: GSK1358820 100 U/GSK1358820 100 U

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With UTI: Placebo/GSK1358820 100 U

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With UTI: GSK1358820 100 U/GSK1358820 100 U

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in PVR Urine Volume

PVR urine volume was assessed by ultrasound or bladder scan after participants perform a voluntary void according to the study schedule. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as any visit value minus Baseline value.

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in PVR Urine Volume: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in PVR Urine Volume: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in PVR Urine Volume: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in PVR Urine Volume: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Number of Participants Using Clean Intermittent Catheterization (CIC) for Urinary Retention or Elevated PVR

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: Placebo/GSK1358820 100 U

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: GSK1358820 100 U/GSK1358820 100 U

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: Placebo/GSK1358820 100 U

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: GSK1358820 100 U/GSK1358820 100 U

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound

The kidney and bladder ultrasound was performed in order to assess the presence of stones in the kidneys and bladder, an ultrasound of these structures (with the bladder at least half full) was performed. Participants with abnormal findings after kidney and bladder ultrasound have been presented.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: Placebo/GSK1358820 100 U

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: GSK1358820 100 U/GSK1358820 100 U

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Single 12-lead ECGs were obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS and QT interval. QT interval corrected for heart rate (QTc) value is machine-read or manually over-read. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal ECG Findings

Single 12-lead ECGs were obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS and QT interval. QTc value is machine-read or manually over-read. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal ECG Findings

Single 12-lead ECGs were obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS and QT interval. QTc value is machine-read or manually over-read. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Full Information

NCT ID

NCT02820844

First Posted

June 29, 2016

Last Updated

November 13, 2020

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT02820844

Brief Title

Efficacy and Safety of GSK1358820 in Subjects With Overactive Bladder

Official Title

A Phase III Study to Evaluate the Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Overactive Bladder

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

August 10, 2016 (Actual)

Primary Completion Date

March 6, 2018 (Actual)

Study Completion Date

November 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

GSK1358820 is a botulinum neurotoxin A complex that has been approved for the treatment of overactive bladder (OAB) in several countries, however, it has not been approved for OAB treatment in Japan. This study has been planned to evaluate the efficacy and safety of GSK1358820 in Japanese OAB patients with urinary incontinence whose symptoms have not been adequately managed with other medications for OAB. The primary objective of this study is to evaluate the superiority of a single dose treatment of GSK1358820 100 units (U) compared with placebo. The study comprises a screening phase up to 28 days, followed by a double-blind treatment phase of 12 to 48 weeks wherein subjects will receive a single treatment of either GSK1358820 100 U injection or Placebo injection, in a ratio of 1:1, with further stratification within the treatment arms according to the number of urinary urge incontinence episodes during screening. Subjects meeting the criteria for re-treatment will receive a second and third treatment. Each re-treatment will be with open-label GSK1358820 100 U injection, and will be spaced at least 12 weeks from the previous treatment. The total duration of participation for any subject will not exceed 52 weeks, including screening and the 48-week treatment period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urinary Bladder, Overactive

Keywords

Overactive bladder, Botulinum toxin type A, Urinary incontinence

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

250 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK1358820 Injection 100 U

Arm Type

Experimental

Arm Description

Arm Title

Placebo Injection

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

GSK1358820

Intervention Description

GSK1358820 injection contains botulinum toxin type A (100 U), sodium chloride (0.9 milligrams [mg]), and human serum albumin (0.5 mg). 10 mL of the drug will be injected at 20 sites (0.5 mL at each site) in the detrusor muscle, spaced approximately 1 centimeter (cm) apart. The injection will be administered under local anesthesia, via cystoscopy. Permitted anesthesia options for cystoscopy are intraurethral lidocaine (or similar) gel, and for treatment administration, installation of 1-2% lidocaine (or similar anesthetic) into the bladder.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo injection is made up of sodium chloride (0.9 mg). 10 mL of the injection will be injected at 20 sites (0.5 mL at each site) in the detrusor muscle, spaced approximately 1 cm apart. The injection will be administered under local anesthesia, via cystoscopy. Permitted anesthesia options for cystoscopy are intraurethral lidocaine (or similar) gel, and for treatment administration, installation of 1-2% lidocaine (or similar anesthetic) into the bladder.

Intervention Type

Drug

Intervention Name(s)

Antibiotic therapy

Intervention Description

Subjects will use prophylactic antibiotic therapy approved for the indication of UTIs, at the discretion of the investigator, with the exception of those in the class of aminoglycosides. The therapy will begin 1 to 3 days prior to the administration of study treatment, and continue for 1 to 3 days following the treatment.

Intervention Type

Other

Intervention Name(s)

Bladder diary

Intervention Description

The bladder diary is a self-reporting tool to record subject's data on micturition. Subjects will enter data in the diary over 3 consecutive days. During Screening, data will be collected within 28 days prior to first treatment. During treatment periods, data will be collected within a week prior to each scheduled visit. The bladder diary will capture the following information: 1) Date and time of urinary episode, 2) episodes of micturition, 3) episodes of urinary incontinence, 4) episodes of urgency, 5) intensity of urgency, 6) episodes of nocturia, 7) use of CIC, and 8) urine volume. Diary data will not be collected when a subject experiences symptoms of a UTI.

Intervention Type

Other

Intervention Name(s)

King's Health Questionnaire (KHQ)

Intervention Description

The KHQ will assess the impact of urinary incontinence on QOL. It is a questionnaire with 21 items and the following 9 domains: 1) General health, 2) Incontinence impact, 3) Role limitations, 4) Physical limitations, 5) Social limitations, 6) Personal relationships, 7) Emotion, 8) Sleep/energy, 9) Severity measure. The items are answered by subjects themselves, and scores are summated using a defined algorithm.

Intervention Type

Other

Intervention Name(s)

Overactive Bladder Symptom Score (OABSS)

Intervention Description

The OABSS will comprehensively assess symptoms of OAB, such as frequency of micturition, nocturia, urinary urgency, and urge incontinence. It consists of 4 questions which will be responded by subjects themselves, by selecting the most appropriate answer for each question.

Intervention Type

Other

Intervention Name(s)

Treatment Benefit Scale (TBS)

Intervention Description

The TBS consists of one question ("My condition has"), to which the subject will answer by selecting one of the following responses: greatly improved, improved, not changed, worsened. The TBS will assess treatment benefit of GSK1358820.

Primary Outcome Measure Information:

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in the Daily Average Number of Urinary Incontinence Episodes at Week 12 After the First Treatment

Description

Time Frame

Baseline (Pre-dose on Day 1) and Week 12 in Treatment Cycle 1

Secondary Outcome Measure Information:

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in the Average Volume Voided Per Micturition at Week 12 After the First Treatment

Description

Time Frame

Baseline (Pre-dose on Day 1) and Week 12 in Treatment Cycle 1

Title

Treatment Phase 1 (Treatment Cycle 1): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value. FAS2 Population comprised all randomized participants who had at least 1 post-2nd treatment efficacy assessment after 2nd treatment.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline was calculated as any visit value minus Baseline value. FAS3 Population comprised of all randomized participants who had at least 1 post-3rd treatment efficacy assessment after 3rd treatment.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urinary Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes was calculated from bladder diary data recorded by the participants during the 3-day diary collection period by dividing the number of 'Yes' response to the diary question of accidental urinary leakage with number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urinary Urgency Incontinence Episodes

Description

The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Voids

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Voids

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Voids

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Voids

Description

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Voids

Description

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Voids

Description

The daily average number of micturition episodes (voids) were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes response to the diary question of urination into the toilet with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Average Volume Voided Per Micturition

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Average Volume Voided Per Micturition

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Average Volume Voided Per Micturition

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Average Volume Voided Per Micturition

Description

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Average Volume Voided Per Micturition

Description

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Average Volume Voided Per Micturition

Description

The total volume voided was measured and recorded by participants in the bladder diary, over a 24-hour period during the 3-day diary collection period. Volume voided per micturition was determined by dividing the total urine volume collected in 24-hour period by the participants with the number of the urinary volume records which are not missing. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Urgency Episodes

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Urgency Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Urgency Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

Description

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

Description

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Change From Baseline in Daily Average Number of Urgency Episodes

Description

The daily average number of urgency episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of "Yes" response to the diary question of episode associated with a sudden and urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Nocturia Episodes

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Nocturia Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Nocturia Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Description

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Description

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage Changes From Baseline in Daily Average Number of Nocturia Episodes

Description

Nocturia episodes are voids (micturition episodes) that interrupt night sleep. The daily average number of nocturia episodes were calculated from bladder diary data recorded by the participant during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of episodes that awake participants from night sleep with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Percentage change from Baseline was calculated as post-dose visit value minus Baseline, divided by Baseline and multiplied by 100.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Severe Urgency Episodes

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Severe Urgency Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Severe Urgency Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

Description

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

Description

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in Daily Average Number of Severe or Moderate Urgency Episodes

Description

The daily average number of urgency episodes categorized by each urgency intensity as no urgency, mild urgency, moderate urgency and severe urgency. Urgency episodes were calculated by a 4-point scale ranging from '0' (No urgency), '1' (mild urgency), '2' (moderate urgency), '3' (Severe urgency), as part of the bladder diary, during the 3-day diary collection period. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day. Change from Baseline in daily average number of severe or moderate urgency episodes was calculated as any visit value minus Baseline value.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Maximum Urgency Intensity

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Number of Participants With Maximum Urgency Intensity

Description

Time Frame

Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Number of Participants With Maximum Urgency Intensity

Description

Time Frame

Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Number of Participants With Improvement and Worsening in Maximum Urgency Intensity From Baseline

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants Attaining 100 Percent (%), >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Incontinence Episodes

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/ urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants Attaining 100%, >=75% and >=50% Reduction From Baseline in the Daily Average of Urinary Urgency Incontinence Episodes

Description

Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1)", excluding the day of visit (this period was called the '3-day diary collection period'). The daily average number of urge incontinence episodes were calculated from bladder diary data recorded by the participants during the 3-day diary collection period, by dividing the number of 'Yes' response to the diary question of accidental urinary leakage and sudden/urgent need to urinate with the number of valid diary days in the visit. Baseline is the latest pre-dose 3-day diary assessment which has at least one valid diary day.

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Time to Qualification for Retreatment

Description

Time Frame

Up to 36 weeks in Treatment Cycle 1

Title

Treatment Phase 1 (Treatment Cycle 1): Time to Request for Retreatment

Description

Time Frame

Up to 36 weeks in Treatment Cycle 1

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 12, Week 24, Week 36 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Change From Baseline in KHQ Domain Scores

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 12, Week 24 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Change From Baseline in KHQ Domain Scores

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 12 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Percentage of Participants With Positive Response on the Treatment Benefit Scale (TBS)

Description

Time Frame

Week 2, Week 6, Week 12, Week 24, Week 36 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Percentage of Participants With Positive Response on the TBS

Description

Time Frame

Week 0, Week 2, Week 6, Week 12, Week 24 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Percentage of Participants With Positive Response on the TBS

Description

Time Frame

Week 0, Week 2, Week 6, Week 12 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Changes From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 12, Week 24, Week 36 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2): Changes From Baseline in OABSS Total Score

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 12, Week 24 and Week 36 in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3): Changes From Baseline in OABSS Total Score

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 12 and Week 24 in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

Description

Time Frame

Up to 48 weeks in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With SAEs and Non-SAEs: Placebo/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With SAEs and Non-SAEs: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With SAEs and Non-SAEs: Placebo/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With SAEs and Non-SAEs: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in SBP and DBP: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in SBP and DBP: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in SBP and DBP: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in SBP and DBP: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Heart Rate

Description

Time Frame

Baseline (Pre-dose on Day 1) and Week 2, Week 6, Week 12, Week 18, Week 24 Week 30, Week 36, Week 42 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Heart Rate: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24 Week 30, Week 36 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Heart Rate: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24 Week 30 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Heart Rate: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Heart Rate: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in Temperature

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Temperature: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in Temperature: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Temperature: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in Temperature: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 12 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Shift From Baseline Relative to Normal Range in Chemistry Results

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 12 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Shift From Baseline Relative to Normal Range in Hematology Parameters

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Description

Time Frame

Baseline (Pre-dose on Day 1) and up to 48 weeks in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1) and up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to Baseline

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1) and up to 48 weeks after 1st treatment

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Urinary Tract Infection (UTI)

Description

Time Frame

Up to 48 weeks in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With UTI: Placebo/GSK1358820 100 U

Description

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With UTI: GSK1358820 100 U/GSK1358820 100 U

Description

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With UTI: Placebo/GSK1358820 100 U

Description

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With UTI: GSK1358820 100 U/GSK1358820 100 U

Description

A urine culture and sensitivity test were performed when urinalysis results with a urine reagent strip are suggestive of a UTI (positive nitrites or leukocyte esterase). UTI was recorded as an AE, irrespective of symptoms when the result of urine culture was positive (with the presence of bacteriuria with >=10^5 CFU/mL and leukocyturia with >5 per high power field was noted.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in PVR Urine Volume

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 (study exit or withdrawal visit) in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in PVR Urine Volume: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 2)- Change From Baseline in PVR Urine Volume: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in PVR Urine Volume: Placebo/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 2, Week 6, Week 12, Week 18, Week 24 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 2 (Treatment Cycle 3)- Change From Baseline in PVR Urine Volume: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Baseline (Pre-dose of Treatment Cycle 1), Week 2, Week 6, Week 12, Week 18 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants Using Clean Intermittent Catheterization (CIC) for Urinary Retention or Elevated PVR

Description

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Time Frame

Up to 48 weeks in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: Placebo/GSK1358820 100 U

Description

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: GSK1358820 100 U/GSK1358820 100 U

Description

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: Placebo/GSK1358820 100 U

Description

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants Using CIC for Urinary Retention or Elevated PVR: GSK1358820 100 U/GSK1358820 100 U

Description

Participants who had used CIC at least once after the first treatment with the reason for urinary retention or elevated PVR have been presented.

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound

Description

Time Frame

Up to 48 weeks in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: Placebo/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: Placebo/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal Findings Undergoing Kidney and Bladder Ultrasound: GSK1358820 100 U/GSK1358820 100 U

Description

Time Frame

Up to 48 weeks after 1st treatment

Title

Treatment Phase 1 (Treatment Cycle 1): Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Description

Time Frame

Baseline (Pre-dose on Day 1), Week 12 and Week 48 in Treatment Cycle 1

Title

Treatment Phase 2 (Treatment Cycle 2)- Number of Participants With Abnormal ECG Findings

Description

Single 12-lead ECGs were obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS and QT interval. QTc value is machine-read or manually over-read. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Time Frame

Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 2

Title

Treatment Phase 2 (Treatment Cycle 3)- Number of Participants With Abnormal ECG Findings

Description

Single 12-lead ECGs were obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS and QT interval. QTc value is machine-read or manually over-read. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Time Frame

Week 12 and Week 48 (48 weeks after 1st treatment or withdrawal visit) in Treatment Cycle 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged >=20 years at the time of signing the informed consent. Subject has symptoms of OAB (frequency and urgency) with urinary incontinence for a period of at least 6 months immediately prior to screening, determined by documented subject history. Subject has not been adequately managed with one or more medications (that is, anticholinergics or beta-3 adrenergic receptor agonist) for treatment of their OAB symptom. 'Not adequately managed' is defined as: An inadequate response after at least a 4-week period of OAB medication(s) on an approved optimized dose(s), that is, subject is still incontinent despite medication(s) for OAB; or limiting side effects (that is, condition that subject reduced dosage or discontinued the medication due to side effect after at least a 2-week period of OAB medication(s) on an approved optimized dose(s)). Subject who experiences all of the following, in the 3-day subject bladder diary completed during the screening phase: >= 3 episodes of urinary urgency incontinence, with no more than one urgency incontinence-free day urinary frequency (defined as an average of >= 8 micturitions [toilet voids] per day, that is, a total of >= 24 micturitions) Subject is willing to use clean intermittent catheterization (CIC) to drain urine if it is determined to be necessary by the investigator (or subinvestigator). Body weight >=40 kilograms (kg) at screening. Males or females: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until the study exit: Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the contraceptive options below: Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; or oral contraceptive, either combined or progestogen alone. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine or serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: • Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. • Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until the study exit. This list of highly effective methods (approved in Japan) is provided below, and it does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. Subject has given signed informed consent, including compliance with the requirements and restrictions listed in the consent form and in this protocol (example, using the toilet without assistance, complete bladder diaries and questionnaires, is able to collect volume voided per micturition measurements over a 24-hour period, and attend all study visits in the opinion of the investigator (or subinvestigator). Exclusion Criteria: Subject has symptoms of OAB due to any known neurological reason (example, spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer's disease, Parkinson's disease, etc.) Subject has a predominance of stress incontinence determined by subject history. Subject has a history or evidence of any diseases, functional abnormalities or bladder surgery, other than OAB, that may have affected bladder function including but not limited to: Bladder stones (including bladder stone surgery) within 6 months prior to screening or confirmed occurrence of bladder stones at the screening phase Surgery (including minimally invasive surgery) within 1 year of screening for stress incontinence or pelvic organ prolapse Current use of an electrostimulation/neuromodulation device for treatment of urinary incontinence. Note: Use of any implantable device is prohibited within 4 weeks prior to initiation of screening phase and throughout the study period. Use of any external device is prohibited within 7 days prior to the start of the screening phase History of interstitial cystitis, in the opinion of the investigator (or subinvestigator) Past or current evidence of hematuria due to urological/renal pathology or uninvestigated hematuria. Subjects with investigated hematuria may enter the study if urological/renal pathology has been ruled out to the satisfaction by the investigator (or subinvestigator). Past or current history of bladder cancer or other urothelial malignancy, positive result of urine cytology or uninvestigated suspicious urine cytology results at the Screening phase. Suspicious urine cytology abnormalities require that bladder cancer or other urothelial malignancy has been ruled out to the satisfaction of the investigator according to local site practice. An active genital infection, other than genital warts, either concurrently or within 4 weeks prior to Screening Male with previous or current diagnosis of prostate cancer or a prostate specific antigen (PSA) level of >10 nanograms (ng)/mL at Screening. Subjects with a PSA level of >= 4 ng/mL but <= 10 ng/mL must have prostate cancer ruled out to the satisfaction of the investigator (or subinvestigator) according to local site practice. Evidence of urethral and/or bladder outlet obstruction, in the opinion of the investigator (or subinvestigator) Subject has a history of 2 or more urinary tract infections (UTIs) within 6 months of initiation of Treatment phase 1 (Week 0) or current administration of prophylactic antibiotics to prevent chronic UTIs Subject has a positive urine dipstick reagent strip test at initiation of Treatment phase 1 (Week 0) for nitrites or leukocyte esterase, or who are considered by the investigator (or subinvestigator) to have UTI. Subject has a serum creatinine level >2 times the upper limit of normal (ULN) at screening. Alanine aminotransferase (ALT) > 2xULN; and bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening. Subject has current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Notes: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis Chronic stable hepatitis B and C (example, presence of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody [HCVAb] test result within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria QT corrected (QTc) > 450 milliseconds (msec) or QTc > 480 msec in subjects with Bundle Branch Block from the result of electrocardiogram (ECG) at screening. Notes: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial Subject has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diathesis. Subject received anticholinergic, beta-3 adrenergic receptor agonist or any other medications or therapies to treat symptoms of OAB, including nocturia, within 7 days prior to the start of the screening phase. Subject has been treated with any intravesical pharmacologic agent (example, capsaicin, resiniferatoxin) for OAB symptoms within 12 months prior to initiation of Treatment phase 1 (Week 0). Subject has previous or current use of botulinum toxin therapy of any serotype for the treatment of any urological condition. Subject has previous use within 12 weeks prior to initiation of Treatment phase 1 (Week 0) or current use of botulinum toxin therapy of any serotype for any non-urological condition or beauty care. Subject has been immunized for botulinum toxin of any serotype. Subject cannot withhold any antiplatelet or anticoagulant therapy or medications with anticoagulative effects for 3 days prior to initiation of Treatment phase 1 (Week 0). Some medications may need to be withheld for >3 days, per clinical judgment of the investigator (or subinvestigator). Subject has not initiated appropriate antibiotic medication 1 to 3 days prior to the initiation of Treatment phase 1 (Week 0). Subject uses CIC or indwelling catheter to manage their urinary incontinence. Subject has a history of sensitivity to any of the study medications, medications used in the study (including anesthesia), or their components or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Subject has any medical condition that may put them at increased risk with exposure to GSK1358820 including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis. Females who are pregnant, nursing or planning a pregnancy during the study. Subject has a PVR urine volume of >100 mL at screening phase. The PVR measurement can be repeated once; the subject is to be excluded if the repeated measure is above 100 mL. Subject has had urinary retention or an elevated PVR urine volume within 6 months of screening that has been treated with an intervention (such as catheterization). Voiding difficulties as a result of surgical procedures that resolved within 24 hours are not exclusionary. Subject has a 24-hour total volume of urine voided >3000 mL of urine collected over 24 consecutive hours during the 3-day bladder diary collection period in the Screening phase. Subject is currently participating in or has previously participated in another therapeutic study within 30 days prior to the start of the Screening phase. Subject has any condition or situation which, in the investigator's (or subinvestigator's) opinion, puts the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

466-8560

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

474-8511

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

264-0017

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

270-0034

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

270-1694

Country

Japan

Facility Name

GSK Investigational Site

City

Fukui

ZIP/Postal Code

910-1193

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

802-8517

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

810-0001

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

814-0022

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

815-8588

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

816-0943

Country

Japan

Facility Name

GSK Investigational Site

City

Gifu

ZIP/Postal Code

502-8511

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

GSK Investigational Site

City

Ibaraki

ZIP/Postal Code

309-1793

Country

Japan

Facility Name

GSK Investigational Site

City

Ibaraki

ZIP/Postal Code

310-0011

Country

Japan

Facility Name

GSK Investigational Site

City

Ishikawa

ZIP/Postal Code

920-8641

Country

Japan

Facility Name

GSK Investigational Site

City

Kagoshima

ZIP/Postal Code

890-0073

Country

Japan

Facility Name

GSK Investigational Site

City

Kagoshima

ZIP/Postal Code

890-8520

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

227-8501

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

231-0861

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

252-0392

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

612-8555

Country

Japan

Facility Name

GSK Investigational Site

City

Miyagi

ZIP/Postal Code

980-0803

Country

Japan

Facility Name

GSK Investigational Site

City

Miyagi

ZIP/Postal Code

981-0501

Country

Japan

Facility Name

GSK Investigational Site

City

Nagasaki

ZIP/Postal Code

852-8501

Country

Japan

Facility Name

GSK Investigational Site

City

Niigata

ZIP/Postal Code

950-8725

Country

Japan

Facility Name

GSK Investigational Site

City

Okayama

ZIP/Postal Code

700-8558

Country

Japan

Facility Name

GSK Investigational Site

City

Okayama

ZIP/Postal Code

710-8522

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

542-0086

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

554-0012

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

564-0013

Country

Japan

Facility Name

GSK Investigational Site

City

Shiga

ZIP/Postal Code

520-2192

Country

Japan

Facility Name

GSK Investigational Site

City

Shizuoka

ZIP/Postal Code

431-3192

Country

Japan

Facility Name

GSK Investigational Site

City

Tochigi

ZIP/Postal Code

321-0293

Country

Japan

Facility Name

GSK Investigational Site

City

Tokushima

ZIP/Postal Code

770-8503

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

101-8309

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

113-8655

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

116-8567

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

135-8577

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

162-8655

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

164-8541

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

173-8610

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

181-8611

Country

Japan

Facility Name

GSK Investigational Site

City

Tottori

ZIP/Postal Code

680-0903

Country

Japan

Facility Name

GSK Investigational Site

City

Tottori

ZIP/Postal Code

683-8504

Country

Japan

Facility Name

GSK Investigational Site

City

Toyama

ZIP/Postal Code

937-0042

Country

Japan

Facility Name

GSK Investigational Site

City

Yamagata

ZIP/Postal Code

990-0834

Country

Japan

Facility Name

GSK Investigational Site

City

Yamanashi

ZIP/Postal Code

409-3898

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study is available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20738

Citations:

PubMed Identifier

31957922

Citation

Yokoyama O, Honda M, Yamanishi T, Sekiguchi Y, Fujii K, Nakayama T, Mogi T. OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis). Int J Urol. 2020 Mar;27(3):227-234. doi: 10.1111/iju.14176. Epub 2020 Jan 20.

Results Reference

background

PubMed Identifier

34292493

Citation

Yokoyama O, Honda M, Yamanishi T, Sekiguchi Y, Fujii K, Kinoshita K, Nakayama T, Ueno A, Mogi T. Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial. Int Urol Nephrol. 2021 Nov;53(11):2243-2250. doi: 10.1007/s11255-021-02962-z. Epub 2021 Jul 22.

Results Reference

derived

Learn more about this trial

Efficacy and Safety of GSK1358820 in Subjects With Overactive Bladder

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Efficacy and Safety of GSK1358820 in Subjects With Overactive Bladder

Urinary Bladder, Overactive

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial