Back to resultsA Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
Primary Purpose
Overactive Bladder, Overactive Urinary Bladder
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Vibegron
Tolterodine ER
Placebo (vibegron)
Placebo (tolterodine ER)
Prophylactic Antibiotic
Sponsored by
About this trial
This is an interventional treatment trial for Overactive Bladder
Eligibility Criteria
Inclusion Criteria:
- Non-child bearing potential (status post menopausal or post hysterectomy,oophorectomy or tubal ligation). If of reproductive potential, must be non-pregnant (confirmed via blood test) and agree to use (and/or have their partner use) two acceptable methods of birth control beginning at least 2 weeks prior to administration of the first dose of study drug,throughout the study (including washout intervals between treatment periods/panels) and until at least 2 weeks after administration of the last dose of study drug in the last treatment period.
- Body mass index (BMI) of ≤40 kg/m^2 (ie, not morbidly obese)
- Clinical history of overactive bladder symptoms (OAB) for at least 3 months
- Capable of completing an accurate daily diary for reporting purposes
Exclusion Criteria:
- Mentally or legally incapacitated, such as significant emotional problems (other than situational depression) or diagnosed with a significant psychiatric disorder during the past 5-10 years
- Other types of urinary incontinence (ie,stress or mixed)
- History (current or past)of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain or Stage III or greater pelvic organ prolapse
- Other types of kidney/urinary bladder disease/obstruction or infection. Participants with with a history of uncomplicated kidney stones may be enrolled in the study at the discretion of the investigator
- Inability to control bowel movements
- History of narrow angle glaucoma, immunocompromise, stroke, chronic seizures, major neurological disorders and/or other serious and chronic organ-system health conditions (ie, heart disease)
- Urinary catheter, either permanent or intermittent placement
- Failure to meet medication profile requirements or directives required for study eligibility
- Condition for which there is a warning, contraindication, or precaution against the use of tolterodine ER or anticipates the use of prescription medications contraindicated with the use of tolterodine ER
- Daily alcohol or caffeine intake exceeds study requirements (for alcohol: defined as greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day; and for caffeine: defined as greater than 3 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee,tea, cola, or other caffeinated beverages (ie, Red Bull) per day
- Inability to refrain from smoking throughout the study's duration
- Illicit drug use
- Recent surgery or recent participation in another clinical trial
- Severe, frequent allergies or history of life-threatening reactions or intolerability to prescription or non prescription medications or food
- Intended or unintended extended absence or exposure to significant change in time zone or sleep schedule (ie, transmeridian travel or shift work) that will interfere with accurate completion of scheduled daily diary entries
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Active Comparator
Experimental
Arm Label
Vibegron 100 mg + tolterodine ER 4 mg → placebo
Placebo → vibegron 100 mg
Placebo → tolterodine ER 4 mg
Placebo → vibegron 50 mg
Arm Description
During Treatment Period 1, participants will receive 7 days of once-daily vibegron 100 mg and tolterodine extended-release (ER) 4 mg. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER.
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily vibegron 100 mg and placebo to match tolterodine ER.
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily tolterodine 4 mg and placebo to match vibegron.
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily vibegron 50 mg and placebo to match tolterodine ER.
Outcomes
Primary Outcome Measures
Fold-change From Baseline in Maximum Cystometric Capacity Post-dose on Day 7
Filling cystometry procedures were performed pre-dose on Day 1 and post-dose on Day 7 in each treatment period. Individual values in fold-change from baseline and post-dose on Day 7 will be natural log-transformed and evaluated with a linear mixed effects model having period and treatment as fixed effects and participant as a random effect.
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Number of Participants Who Discontinued Use of Study Drug Due to an AE
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. The number of participants who discontinued study drug due to an AE were reported.
Secondary Outcome Measures
Fold-change From Baseline in Volume of Urine at First Desire to Void Post-dose on Day 7
Filling cystometry procedures were performed pre-dose on Day 1 and post-dose on Day 7 in each treatment period. Individual values in fold-change from baseline and post-dose on Day 7 will be natural log-transformed and evaluated with a linear mixed effects model having period and treatment as fixed effects and participant as a random effect.
Full Information
NCT ID
NCT01500382
First Posted
December 22, 2011
Last Updated
December 3, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01500382
Brief Title
A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
Official Title
A Placebo and Active-Comparator Controlled Multiple-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of MK-4618 in Patients With Overactive Bladder
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated early due to insufficient recruitment.
Study Start Date
February 27, 2012 (Actual)
Primary Completion Date
January 2, 2013 (Actual)
Study Completion Date
January 2, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is designed to investigate the effects of the investigational drug vibegron (MK-4618) compared to placebo on maximum urinary bladder capacity in women with overactive bladder. The study will also evaluate the safety and tolerability of multiple oral doses of vibegron in women with overactive bladder. Overactive bladder is best described as urgency and frequency of urination, with or without involuntary urination and/or the need to awaken during the night to urinate.
The primary efficacy hypothesis is that vibegron is superior to placebo with respect to change from baseline in maximum cystometric capacity at 2 hours postdose on Day 7 (i.e., steady state) in participants with overactive bladder. A true mean increase (vibegron/placebo) of 25% in bladder volume is expected.
The primary safety hypothesis is that administration of multiple oral doses of vibegron is sufficiently well-tolerated in participants with overactive bladder, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.
Detailed Description
Participants will be randomized in each of 2 treatment periods to 1 of 4 possible treatments, which will be administered in double-dummy fashion, and participants will undergo urodynamic procedures prior to dosing on Day 1 and after 7 days of treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overactive Bladder, Overactive Urinary Bladder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vibegron 100 mg + tolterodine ER 4 mg → placebo
Arm Type
Experimental
Arm Description
During Treatment Period 1, participants will receive 7 days of once-daily vibegron 100 mg and tolterodine extended-release (ER) 4 mg. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER.
Arm Title
Placebo → vibegron 100 mg
Arm Type
Experimental
Arm Description
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily vibegron 100 mg and placebo to match tolterodine ER.
Arm Title
Placebo → tolterodine ER 4 mg
Arm Type
Active Comparator
Arm Description
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily tolterodine 4 mg and placebo to match vibegron.
Arm Title
Placebo → vibegron 50 mg
Arm Type
Experimental
Arm Description
During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily vibegron 50 mg and placebo to match tolterodine ER.
Intervention Type
Drug
Intervention Name(s)
Vibegron
Other Intervention Name(s)
MK-4618
Intervention Description
Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.
Intervention Type
Drug
Intervention Name(s)
Tolterodine ER
Other Intervention Name(s)
Detrol LA™
Intervention Description
Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.
Intervention Type
Other
Intervention Name(s)
Placebo (vibegron)
Intervention Description
Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
Intervention Type
Other
Intervention Name(s)
Placebo (tolterodine ER)
Intervention Description
Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
Intervention Type
Drug
Intervention Name(s)
Prophylactic Antibiotic
Other Intervention Name(s)
Levaquin, Biocef, Ed A-Ceph, Keflex, Keftab, Panixine DisperDose, Zartan
Intervention Description
A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.
Primary Outcome Measure Information:
Title
Fold-change From Baseline in Maximum Cystometric Capacity Post-dose on Day 7
Description
Filling cystometry procedures were performed pre-dose on Day 1 and post-dose on Day 7 in each treatment period. Individual values in fold-change from baseline and post-dose on Day 7 will be natural log-transformed and evaluated with a linear mixed effects model having period and treatment as fixed effects and participant as a random effect.
Time Frame
Baseline (pre-dose Day 1) and Day 7 (post-dose)
Title
Number of Participants Who Experienced an Adverse Event (AE)
Description
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Time Frame
Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)
Title
Number of Participants Who Discontinued Use of Study Drug Due to an AE
Description
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. The number of participants who discontinued study drug due to an AE were reported.
Time Frame
Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)
Secondary Outcome Measure Information:
Title
Fold-change From Baseline in Volume of Urine at First Desire to Void Post-dose on Day 7
Description
Filling cystometry procedures were performed pre-dose on Day 1 and post-dose on Day 7 in each treatment period. Individual values in fold-change from baseline and post-dose on Day 7 will be natural log-transformed and evaluated with a linear mixed effects model having period and treatment as fixed effects and participant as a random effect.
Time Frame
Baseline (pre-dose Day 1) and Day 7 (post-dose)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Non-child bearing potential (status post menopausal or post hysterectomy,oophorectomy or tubal ligation). If of reproductive potential, must be non-pregnant (confirmed via blood test) and agree to use (and/or have their partner use) two acceptable methods of birth control beginning at least 2 weeks prior to administration of the first dose of study drug,throughout the study (including washout intervals between treatment periods/panels) and until at least 2 weeks after administration of the last dose of study drug in the last treatment period.
Body mass index (BMI) of ≤40 kg/m^2 (ie, not morbidly obese)
Clinical history of overactive bladder symptoms (OAB) for at least 3 months
Capable of completing an accurate daily diary for reporting purposes
Exclusion Criteria:
Mentally or legally incapacitated, such as significant emotional problems (other than situational depression) or diagnosed with a significant psychiatric disorder during the past 5-10 years
Other types of urinary incontinence (ie,stress or mixed)
History (current or past)of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain or Stage III or greater pelvic organ prolapse
Other types of kidney/urinary bladder disease/obstruction or infection. Participants with with a history of uncomplicated kidney stones may be enrolled in the study at the discretion of the investigator
Inability to control bowel movements
History of narrow angle glaucoma, immunocompromise, stroke, chronic seizures, major neurological disorders and/or other serious and chronic organ-system health conditions (ie, heart disease)
Urinary catheter, either permanent or intermittent placement
Failure to meet medication profile requirements or directives required for study eligibility
Condition for which there is a warning, contraindication, or precaution against the use of tolterodine ER or anticipates the use of prescription medications contraindicated with the use of tolterodine ER
Daily alcohol or caffeine intake exceeds study requirements (for alcohol: defined as greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day; and for caffeine: defined as greater than 3 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee,tea, cola, or other caffeinated beverages (ie, Red Bull) per day
Inability to refrain from smoking throughout the study's duration
Illicit drug use
Recent surgery or recent participation in another clinical trial
Severe, frequent allergies or history of life-threatening reactions or intolerability to prescription or non prescription medications or food
Intended or unintended extended absence or exposure to significant change in time zone or sleep schedule (ie, transmeridian travel or shift work) that will interfere with accurate completion of scheduled daily diary entries
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
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