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A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder (SYNERGY II)

Primary Purpose

Urinary Bladder Overactive, Overactive Bladder, Urgency Incontinence

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Solifenacin succinate

Mirabegron

Placebo to match solifenacin

Placebo to match mirabegron

About this trial

This is an interventional treatment trial for Urinary Bladder Overactive focused on measuring Solifenacin Succinate, Mirabegron, Urinary Incontinence, Combination Therapy, Urgency, Nocturia, Overactive Bladder

Eligibility Criteria

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

Inclusion Criteria:

Main Inclusion at Screening (Visit 1):

Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months);
Subject was willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;

Main Inclusion at Randomization (Visit 2):

Subject had a micturition frequency of on average ≥ 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition).
Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period.
Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period.

Exclusion Criteria:

Main Exclusion at Screening (Visit 1):

Subject had clinically significant bladder outflow obstruction at risk of urinary retention;
Subject had significant PVR volume (> 150 mL);
Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor;
Subject has an indwelling catheter or practices intermittent self-catheterization;
Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;

Main Exclusion at Randomization (Visit 2):

Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite).
Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Mirabegron 50 mg

Solifenacin 5 mg

Solifenacin 5 mg + Mirabegron 50 mg

Arm Description

Participants received mirabegron 50 mg once a day for 52 weeks.

Participants received solifenacin 5 mg once a day for 52 weeks.

Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

A TEAE was defined as an adverse event (AE) observed after taking the first dose of double-blind treatment until 14 days after taking the last dose of double-blind treatment for non-serious AEs and until 30 days after taking the last dose of double-blind treatment for serious adverse events (SAEs). This included abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of each AE was defined according to the following: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities).

Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours

A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and week 52 clinic visits.

Secondary Outcome Measures

Change From Baseline to EoT in Mean Volume Voided Per Micturition

The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.

Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.

Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours

Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit

The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period prior to each visit with no incontinence episodes recorded.

Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit

The number of incontinence-free days with < 8 micturitions per day was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours

An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.

Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceeded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours

Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day.

Change From Baseline to EoT in Corrected Micturition Frequency

Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. Corrected micturition frequency was calculated as the baseline mean volume voided per micturition multiplied by the baseline mean number of micturitions per 24 hours divided by the mean volume voided per micturition at EoT.

Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition

The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours

Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode recorded by the participant in the micturition diary for 7 days prior to each visit as 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours

A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit."

Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours

The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit.

Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit

The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit

The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consisted of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each time was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC)

The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.

Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).

Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT

Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility

The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort

The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression

Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed

The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working

Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment

The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes arre expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment

Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the last 3 days of the 7-day micturition diary is reported.

Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT

Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT

Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the 7-day micturition diary is reported.

Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT

The percentage of participants with micturition frequency normalization was defined as participants who had ≥ 8 micturitions/24 hours at baseline and < 8 micturitions/24 hours postbaseline at months 1, 3, 6, 9, 12 and EoT.

Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.

Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The symptom bother portion of the OAB-q consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.

Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The HRQoL portion of the OAB-q consists of 25 HRQoL items comprising 4 HRQoL subscales, each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume

PVR volume was assessed by ultrasonography or a bladder scanner.

Full Information

NCT ID

NCT02045862

First Posted

January 23, 2014

Last Updated

August 16, 2018

Sponsor

Astellas Pharma Europe B.V.

1. Study Identification

Unique Protocol Identification Number

NCT02045862

Brief Title

A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder

Acronym

SYNERGY II

Official Title

A Randomized, Double-Blind, Parallel-Group, Active-Controlled, Multi-center Study to Evaluate the Long-Term Safety and Efficacy of Combination of Solifenacin Succinate With Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Subjects With Overactive Bladder

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

March 17, 2014 (Actual)

Primary Completion Date

September 8, 2016 (Actual)

Study Completion Date

September 8, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Astellas Pharma Europe B.V.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study was to examine how well the combination of two medicines (solifenacin succinate and mirabegron) worked compared to each medicine alone in the treatment of bladder problems, and how safe they were for long term use.

6. Conditions and Keywords

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

Urinary Bladder Overactive, Overactive Bladder, Urgency Incontinence, Urinary Bladder Diseases\Urologic Diseases

Keywords

Solifenacin Succinate, Mirabegron, Urinary Incontinence, Combination Therapy, Urgency, Nocturia, Overactive Bladder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1829 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mirabegron 50 mg

Arm Type

Active Comparator

Arm Description

Participants received mirabegron 50 mg once a day for 52 weeks.

Arm Title

Solifenacin 5 mg

Arm Type

Active Comparator

Arm Description

Participants received solifenacin 5 mg once a day for 52 weeks.

Arm Title

Solifenacin 5 mg + Mirabegron 50 mg

Arm Type

Experimental

Arm Description

Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Intervention Type

Drug

Intervention Name(s)

Solifenacin succinate

Other Intervention Name(s)

Vesicare, Vesitrim, YM905, Vesikur

Intervention Description

Participants received solifenacin 5 mg orally once a day at the same time each day.

Intervention Type

Drug

Intervention Name(s)

Mirabegron

Other Intervention Name(s)

Myrbetriq, YM178, Betmiga, Betanis

Intervention Description

Participants received mirabegron 50 mg orally once a day at the same time each day.

Intervention Type

Drug

Intervention Name(s)

Placebo to match solifenacin

Intervention Description

Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.

Intervention Type

Drug

Intervention Name(s)

Placebo to match mirabegron

Intervention Description

Participants received placebo to match mirabegron 50 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)

Title

Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

Description

Time Frame

Baseline and Week 52

Title

Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours

Description

Time Frame

Baseline and Week 52

Secondary Outcome Measure Information:

Title

Change From Baseline to EoT in Mean Volume Voided Per Micturition

Description

The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.

Time Frame

Baseline and Week 52

Title

Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score

Description

Time Frame

Baseline and Week 52

Title

Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Description

Time Frame

Baseline and Week 52

Title

Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Description

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit

Description

The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period prior to each visit with no incontinence episodes recorded.

Time Frame

Months 1, 3, 6, 9, 12

Title

Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit

Description

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Description

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Description

The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day.

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to EoT in Corrected Micturition Frequency

Description

Time Frame

Baseline and Month 12

Title

Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition

Description

Time Frame

Baseline and Months 3, 6, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Description

A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit.

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit

Description

A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours

Description

The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit

Description

The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

Time Frame

Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit

Description

The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping

Description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern

Description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social

Description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC)

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

Description

Time Frame

Month 12

Title

Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT

Description

Time Frame

Month 12

Title

Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility

Description

Time Frame

Baseline and 12 Months

Title

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care

Description

Time Frame

Baseline and Month 12

Title

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities

Description

Time Frame

Baseline and Month 12

Title

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort

Description

Time Frame

Baseline and Month 12

Title

Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression

Description

Time Frame

Baseline and Month 12

Title

Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed

Description

Time Frame

Baseline and Months 6,12

Title

Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working

Description

Time Frame

Baseline and Months 6, 12

Title

Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment

Description

The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes arre expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

Time Frame

Baseline and Months 6, 12

Title

Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment

Description

Time Frame

Baseline and Months 6, 12

Title

Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Months 1, 3, 6, 9, 12

Title

Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Months 1, 3, 6, 9, 12

Title

Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Description

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Description

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Description

Time Frame

Baseline and Months 1, 3, 6, 9, 12

Title

Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume

Description

PVR volume was assessed by ultrasonography or a bladder scanner.

Time Frame

Baseline and Months 1, 3, 6, 9, 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Main Inclusion at Screening (Visit 1): Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months); Subject was willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings; Main Inclusion at Randomization (Visit 2): Subject had a micturition frequency of on average ≥ 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition). Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period. Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period. Exclusion Criteria: Main Exclusion at Screening (Visit 1): Subject had clinically significant bladder outflow obstruction at risk of urinary retention; Subject had significant PVR volume (> 150 mL); Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor; Subject has an indwelling catheter or practices intermittent self-catheterization; Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs; Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin; Main Exclusion at Randomization (Visit 2): Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite). Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Astellas Pharma Europe B.V.

Official's Role

Study Director

Facility Information:

Facility Name

Site US10049

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Site US10112

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Site US10104

City

Chandler

State/Province

Arizona

ZIP/Postal Code

85224

Country

United States

Facility Name

Site US10021

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85051

Country

United States

Facility Name

Site US10122

City

Anaheim

State/Province

California

ZIP/Postal Code

92801

Country

United States

Facility Name

Site US10082

City

Hawaiian Gardens

State/Province

California

ZIP/Postal Code

90716

Country

United States

Facility Name

Site US10132

City

Los Angeles

State/Province

California

ZIP/Postal Code

90017

Country

United States

Facility Name

Site US10133

City

Los Angeles

State/Province

California

ZIP/Postal Code

90036

Country

United States

Facility Name

Site US10149

City

Paramount

State/Province

California

ZIP/Postal Code

90723

Country

United States

Facility Name

Site US10003

City

San Diego

State/Province

California

ZIP/Postal Code

92120

Country

United States

Facility Name

Site US10106

City

Tarzana

State/Province

California

ZIP/Postal Code

91356

Country

United States

Facility Name

Site US10595

City

Valley Village

State/Province

California

ZIP/Postal Code

91607

Country

United States

Facility Name

Site US10053

City

Wheat Ridge

State/Province

Colorado

ZIP/Postal Code

80033

Country

United States

Facility Name

Site US10060

City

Bradenton

State/Province

Florida

ZIP/Postal Code

34208

Country

United States

Facility Name

Site US10097

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33012

Country

United States

Facility Name

Site US10148

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33016

Country

United States

Facility Name

Site US10153

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33016

Country

United States

Facility Name

Site US10091

City

Jupiter

State/Province

Florida

ZIP/Postal Code

33458

Country

United States

Facility Name

Site US10150

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34652

Country

United States

Facility Name

Site US10124

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

Site US10134

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Site US10009

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33027

Country

United States

Facility Name

Site US10554

City

Plantation

State/Province

Florida

ZIP/Postal Code

33317

Country

United States

Facility Name

Site US10037

City

Alpharetta

State/Province

Georgia

ZIP/Postal Code

30005

Country

United States

Facility Name

Site US10127

City

Roswell

State/Province

Georgia

ZIP/Postal Code

30076

Country

United States

Facility Name

Site US10120

City

Sandy Springs

State/Province

Georgia

ZIP/Postal Code

30328

Country

United States

Facility Name

Site US10078

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67205

Country

United States

Facility Name

Site US10088

City

Lake Charles

State/Province

Louisiana

ZIP/Postal Code

70601

Country

United States

Facility Name

Site US10025

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71106

Country

United States

Facility Name

Site US10558

City

Hanover

State/Province

Maryland

ZIP/Postal Code

21076

Country

United States

Facility Name

Site US10282

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02131

Country

United States

Facility Name

Site US10114

City

Watertown

State/Province

Massachusetts

ZIP/Postal Code

02472

Country

United States

Facility Name

Site US10110

City

Billings

State/Province

Montana

ZIP/Postal Code

59102

Country

United States

Facility Name

Site US10154

City

Missoula

State/Province

Montana

ZIP/Postal Code

59801

Country

United States

Facility Name

Site US10553

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68510

Country

United States

Facility Name

Site US10002

City

Englewood

State/Province

New Jersey

ZIP/Postal Code

07631

Country

United States

Facility Name

Site US10047

City

Lawrenceville

State/Province

New Jersey

ZIP/Postal Code

08648

Country

United States

Facility Name

Site US10011

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87102

Country

United States

Facility Name

Site US10015

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87109

Country

United States

Facility Name

Site US10026

City

Garden City

State/Province

New York

ZIP/Postal Code

11530

Country

United States

Facility Name

Site US10040

City

Kingston

State/Province

New York

ZIP/Postal Code

12401

Country

United States

Facility Name

Site US10168

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Site US10126

City

Newburgh

State/Province

New York

ZIP/Postal Code

12550

Country

United States

Facility Name

Site US10028

City

Poughkeepsie

State/Province

New York

ZIP/Postal Code

12601

Country

United States

Facility Name

Site US10076

City

Concord

State/Province

North Carolina

ZIP/Postal Code

28025

Country

United States

Facility Name

Site US10129

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27609

Country

United States

Facility Name

Site US10062

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Facility Name

Site US10050

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44122

Country

United States

Facility Name

Site US10067

City

Wadsworth

State/Province

Ohio

ZIP/Postal Code

44281

Country

United States

Facility Name

Site US10109

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

Site US10541

City

Medford

State/Province

Oregon

ZIP/Postal Code

97504

Country

United States

Facility Name

Site US10008

City

Bala-Cynwyd

State/Province

Pennsylvania

ZIP/Postal Code

19004

Country

United States

Facility Name

Site US10017

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19114

Country

United States

Facility Name

Site US10167

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Site US10250

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15236

Country

United States

Facility Name

Site US10248

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15243

Country

United States

Facility Name

Site US10063

City

Uniontown

State/Province

Pennsylvania

ZIP/Postal Code

15401

Country

United States

Facility Name

Site US10012

City

West Reading

State/Province

Pennsylvania

ZIP/Postal Code

19611

Country

United States

Facility Name

Site US10166

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Site US10079

City

Mount Pleasant

State/Province

South Carolina

ZIP/Postal Code

29464

Country

United States

Facility Name

Site US10023

City

Simpsonville

State/Province

South Carolina

ZIP/Postal Code

29681

Country

United States

Facility Name

Site US10101

City

Summerville

State/Province

South Carolina

ZIP/Postal Code

29485

Country

United States

Facility Name

Site US10006

City

Kingsport

State/Province

Tennessee

ZIP/Postal Code

37660

Country

United States

Facility Name

Site US10065

City

Corpus Christi

State/Province

Texas

ZIP/Postal Code

78414

Country

United States

Facility Name

Site US10085

City

Houston

State/Province

Texas

ZIP/Postal Code

77058

Country

United States

Facility Name

Site US10219

City

Houston

State/Province

Texas

ZIP/Postal Code

77094

Country

United States

Facility Name

Site US10093

City

Houston

State/Province

Texas

ZIP/Postal Code

77099

Country

United States

Facility Name

Site US10090

City

Hurst

State/Province

Texas

ZIP/Postal Code

76054

Country

United States

Facility Name

Site US10105

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Site US10111

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Site US10083

City

Virginia Beach

State/Province

Virginia

ZIP/Postal Code

23462

Country

United States

Facility Name

Site US10013

City

Burien

State/Province

Washington

ZIP/Postal Code

98166

Country

United States

Facility Name

Site US10004

City

Mountlake Terrace

State/Province

Washington

ZIP/Postal Code

98043

Country

United States

Facility Name

Site US10155

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

Site US10135

City

Walla Walla

State/Province

Washington

ZIP/Postal Code

99362

Country

United States

Facility Name

Site AU61005

City

Broadmeadow

State/Province

New South Wales

ZIP/Postal Code

2292

Country

Australia

Facility Name

Site AU61007

City

Randwick

State/Province

New South Wales

ZIP/Postal Code

2031

Country

Australia

Facility Name

Site AU61021

City

Randwick

State/Province

New South Wales

ZIP/Postal Code

2031

Country

Australia

Facility Name

Site AU61011

City

Wollongong

State/Province

New South Wales

ZIP/Postal Code

2522

Country

Australia

Facility Name

Site AU61022

City

Brisbane

State/Province

Queensland

ZIP/Postal Code

4152

Country

Australia

Facility Name

Site AU61010

City

Nambour

State/Province

Queensland

ZIP/Postal Code

4560

Country

Australia

Facility Name

Site AU61019

City

Sherwood

State/Province

Queensland

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4075

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Australia

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Daw Park

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South Australia

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5041

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Australia

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Footscray

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Victoria

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3011

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Australia

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Site AU61002

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Parkville

State/Province

Victoria

ZIP/Postal Code

3052

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Australia

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Site AU61004

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Perth

State/Province

Western Australia

ZIP/Postal Code

6009

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Australia

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Site BE32004

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Gent

ZIP/Postal Code

9000

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Belgium

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Roeselare

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8800

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Belgium

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Sint-Truiden

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3800

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Belgium

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Plovdiv

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4003

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Bulgaria

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Ruse

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7000

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Bulgaria

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Sofia

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1431

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Bulgaria

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Sofia

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1606

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Bulgaria

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Edmonton

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Alberta

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T5G 0B7

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Canada

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Vancouver

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Canada

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Saint John

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Canada

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Barrie

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Ontario

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Canada

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Brampton

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Ontario

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Canada

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Brantford

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Ontario

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Canada

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Kitchener

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Ontario

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Canada

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Toronto

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Ontario

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Canada

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Toronto

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Ontario

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Canada

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Drummondville

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Quebec

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Canada

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Levis

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Quebec

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Canada

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Site CA15020

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Montreal

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Quebec

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H4N 3C5

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Canada

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Site CA15027

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Sherbrooke

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Quebec

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J1H 1Z1

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Canada

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Montreal

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Canada

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Quebec

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Canada

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Brno

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Czechia

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Hradec Kralove

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500 02

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Czechia

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Hradec Kralove

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50005

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Czechia

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Olomouc

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772 00

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Czechia

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Ostrava

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Czechia

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Plzen

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32600

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Czechia

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Praha 2

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12808

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Czechia

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Praha 4

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140 00

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Czechia

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Sternberk

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78501

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Czechia

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Usti nad Labem

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40001

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Aarhus

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8200

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Denmark

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Parnu

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80010

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Estonia

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Kouvola

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45200

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Finland

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Munich

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Bavaria

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81377

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Germany

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Bergisch Gladbach

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Northwest

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51427

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Germany

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Duisburg

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NRW

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47179

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Germany

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Lutherstadt Eisleben

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Sachsen Anhalt

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06295

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Germany

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Leipzig

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Sachsen

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04105

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Germany

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Bad Ems

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56130

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Germany

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Duisburg

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47051

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Germany

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Ganderkesee

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27777

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Germany

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Halle (Saale)

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06132

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Germany

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Neustadt I. Sachsen

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01844

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Germany

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Rostock

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Germany

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Sangerhausen

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06526

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Germany

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Kecskemet

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Bacs-Kiskun Megye

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6000

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Hungary

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Pecs

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Baranya Megye

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7621

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Hungary

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Csongrad

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Csongrad Megye

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6640

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Hungary

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Szentes

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Csongrad Megye

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6600

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Hungary

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Site HU36013

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Sopron

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Gyor-Moson Sopron

ZIP/Postal Code

9400

Country

Hungary

Facility Name

Site HU36012

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Veszprem

State/Province

Veszprem Megye

ZIP/Postal Code

8200

Country

Hungary

Facility Name

Site IT39022

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Ancona

ZIP/Postal Code

60126

Country

Italy

Facility Name

Site IT39007

City

Avellino

ZIP/Postal Code

83100

Country

Italy

Facility Name

Site IT39001

City

Latina

ZIP/Postal Code

04100

Country

Italy

Facility Name

Site IT39020

City

Milano

ZIP/Postal Code

20100

Country

Italy

Facility Name

Site KR82004

City

Suwon-si

State/Province

Gyeonggi-do

ZIP/Postal Code

443-721

Country

Korea, Republic of

Facility Name

Site KR82014

City

Bucheon-Si

State/Province

Gyunggido

ZIP/Postal Code

420-767

Country

Korea, Republic of

Facility Name

Site KR82012

City

Seoul

State/Province

Gyunggido

ZIP/Postal Code

143-729

Country

Korea, Republic of

Facility Name

Site KR82010

City

Jeonju-si

State/Province

Jeollabuk-do South Korea

ZIP/Postal Code

561-712

Country

Korea, Republic of

Facility Name

Site KR82006

City

Busan

ZIP/Postal Code

602-715

Country

Korea, Republic of

Facility Name

Site KR82016

City

Busan

ZIP/Postal Code

602-739

Country

Korea, Republic of

Facility Name

Site KR82005

City

Daegu

ZIP/Postal Code

705-717

Country

Korea, Republic of

Facility Name

Site KR82029

City

Daegu

ZIP/Postal Code

705-718

Country

Korea, Republic of

Facility Name

Site KR82019

City

Daejeon

ZIP/Postal Code

301-721

Country

Korea, Republic of

Facility Name

Site KR82023

City

Incheon

ZIP/Postal Code

405760

Country

Korea, Republic of

Facility Name

Site KR82003

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Site KR82021

City

Seoul

ZIP/Postal Code

100-380

Country

Korea, Republic of

Facility Name

Site KR82020

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

Site KR82030

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Site KR82013

City

Seoul

ZIP/Postal Code

134-701

Country

Korea, Republic of

Facility Name

Site KR82017

City

Seoul

ZIP/Postal Code

134-872

Country

Korea, Republic of

Facility Name

Site KR82002

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

Site KR82008

City

Seoul

ZIP/Postal Code

135-720

Country

Korea, Republic of

Facility Name

Site KR82015

City

Seoul

ZIP/Postal Code

136-075

Country

Korea, Republic of

Facility Name

Site KR82001

City

Seoul

ZIP/Postal Code

137-701

Country

Korea, Republic of

Facility Name

Site LV37102

City

Liepaja

ZIP/Postal Code

LV-3401

Country

Latvia

Facility Name

Site LV37103

City

Olaine

ZIP/Postal Code

LV-2114

Country

Latvia

Facility Name

Site LV37105

City

Riga

ZIP/Postal Code

LV-1002

Country

Latvia

Facility Name

Site LT37008

City

Kaunas

ZIP/Postal Code

47144

Country

Lithuania

Facility Name

Site LT37004

City

Kaunas

ZIP/Postal Code

50009

Country

Lithuania

Facility Name

Site LT37011

City

Kaunas

ZIP/Postal Code

LT49449

Country

Lithuania

Facility Name

Site LT37012

City

Klaipeda

ZIP/Postal Code

LT-92288

Country

Lithuania

Facility Name

Site LT37010

City

Vilnius

ZIP/Postal Code

10207

Country

Lithuania

Facility Name

Site LT37003

City

Vilnius

ZIP/Postal Code

LT-01118

Country

Lithuania

Facility Name

Site LT37007

City

Vilnius

ZIP/Postal Code

LT-08661

Country

Lithuania

Facility Name

Site LT37009

City

Vilnius

ZIP/Postal Code

LT-09108

Country

Lithuania

Facility Name

Site MY60002

City

Petaling Jaya

ZIP/Postal Code

47500

Country

Malaysia

Facility Name

Site MX52003

City

Mexico City

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ZIP/Postal Code

06700

Country

Mexico

Facility Name

Site NL31006

City

Enschede

State/Province

ZIP/Postal Code

7513ER

Country

Netherlands

Facility Name

Site NL31002

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Site NL31005

City

Nijmegen

ZIP/Postal Code

6532 SZ

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Netherlands

Facility Name

Site NL31010

City

Sneek

ZIP/Postal Code

8601 ZK

Country

Netherlands

Facility Name

Site NZ64001

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Christchurch

State/Province

Canterbury

ZIP/Postal Code

8013

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New Zealand

Facility Name

Site NZ64002

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Nelson

ZIP/Postal Code

7010

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New Zealand

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Tauranga

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3140

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New Zealand

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Whangarei

ZIP/Postal Code

0112

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New Zealand

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Alesund

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6003

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Norway

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Hamar

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2317

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Norway

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Lierskogen

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3420

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Norway

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15-351

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Poland

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Chorzow

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41-500

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Poland

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Gdynia

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81-384

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Poland

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Lodz

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90-302

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Poland

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Lublin

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20-632

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Poland

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41-400

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Poland

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Opole

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45-086

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Poland

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Piaseczno

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05-500

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Poland

Facility Name

Site PL48012

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Warsaw

ZIP/Postal Code

00-909

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Poland

Facility Name

Site PL48003

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Warszawa

ZIP/Postal Code

02-507

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Poland

Facility Name

Site PL48001

City

Warszawa

ZIP/Postal Code

02-929

Country

Poland

Facility Name

Site PL48019

City

Wrocław

ZIP/Postal Code

50-088

Country

Poland

Facility Name

Site RO40014

City

Cluj-Napoca

State/Province

Cluj

ZIP/Postal Code

400046

Country

Romania

Facility Name

Site RO40004

City

Bucuresti

ZIP/Postal Code

042122

Country

Romania

Facility Name

Site RO40001

City

Bucuresti

ZIP/Postal Code

50659

Country

Romania

Facility Name

Site RO40005

City

Bucuresti

ZIP/Postal Code

50659

Country

Romania

Facility Name

Site RO40010

City

Sibiu

ZIP/Postal Code

550245

Country

Romania

Facility Name

Site RO40002

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Timisoara

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300736

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Romania

Facility Name

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Kazan

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420097

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Russian Federation

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Penza

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440026

Country

Russian Federation

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Site RU70019

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Saint Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

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Site RU70002

City

Saint Petersburg

ZIP/Postal Code

197089

Country

Russian Federation

Facility Name

Site RU70022

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Saint Petersburg

ZIP/Postal Code

198103

Country

Russian Federation

Facility Name

Site RU70014

City

St. Petersburg

ZIP/Postal Code

199178

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Russian Federation

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Site RU70018

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Ufa

ZIP/Postal Code

450096

Country

Russian Federation

Facility Name

Site SG65002

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Singapore

ZIP/Postal Code

169608

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Singapore

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Site SG65003

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Singapore

ZIP/Postal Code

229899

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Singapore

Facility Name

Site SK42105

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Bratislava

ZIP/Postal Code

82101

Country

Slovakia

Facility Name

Site SK42107

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Kosice

ZIP/Postal Code

04001

Country

Slovakia

Facility Name

Site SK42101

City

Kosice

ZIP/Postal Code

04013

Country

Slovakia

Facility Name

Site SK42103

City

Nitra

ZIP/Postal Code

949 01

Country

Slovakia

Facility Name

Site SK42108

City

Poprad

ZIP/Postal Code

05801

Country

Slovakia

Facility Name

Site SK42104

City

Prešov

ZIP/Postal Code

080 01

Country

Slovakia

Facility Name

Site SK42102

City

Trencin

ZIP/Postal Code

91101

Country

Slovakia

Facility Name

Site SK42106

City

Trencin

ZIP/Postal Code

91101

Country

Slovakia

Facility Name

Site SI38604

City

Murska Sobota

ZIP/Postal Code

9000

Country

Slovenia

Facility Name

Site ZA27001

City

Centurion

State/Province

Gauteng

ZIP/Postal Code

0157

Country

South Africa

Facility Name

Site ZA27002

City

Roodepoort

State/Province

Gauteng

ZIP/Postal Code

1709

Country

South Africa

Facility Name

Site ZA27006

City

Durban

State/Province

Kwa Zulu Natal

ZIP/Postal Code

4001

Country

South Africa

Facility Name

Site ZA27013

City

Meyerspark

State/Province

Pretoria

ZIP/Postal Code

0184

Country

South Africa

Facility Name

Site ZA27007

City

Paarl

State/Province

Western Cape

ZIP/Postal Code

7646

Country

South Africa

Facility Name

Site ES34004

City

Madrid

ZIP/Postal Code

28031

Country

Spain

Facility Name

Site ES34015

City

Madrid

ZIP/Postal Code

28044

Country

Spain

Facility Name

Site ES34009

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Site ES34002

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Site SE46007

City

Boras

ZIP/Postal Code

506 30

Country

Sweden

Facility Name

Site SE46005

City

Malmo

ZIP/Postal Code

211 52

Country

Sweden

Facility Name

Site SE46016

City

Stockholm

ZIP/Postal Code

111 57

Country

Sweden

Facility Name

Site SE46012

City

Stockholm

ZIP/Postal Code

141 86

Country

Sweden

Facility Name

Site SE46003

City

Stockholm

ZIP/Postal Code

182 88

Country

Sweden

Facility Name

Site SE46009

City

Uppsala

ZIP/Postal Code

753 19

Country

Sweden

Facility Name

Site TH66008

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

Site TH66009

City

Khon Kaen

ZIP/Postal Code

40002

Country

Thailand

Facility Name

Site UA38002

City

Cherenigiv

ZIP/Postal Code

14034

Country

Ukraine

Facility Name

Site UA38015

City

Chernivtsi

ZIP/Postal Code

58002

Country

Ukraine

Facility Name

Site UA38013

City

Dnepropetrovsk

ZIP/Postal Code

49005

Country

Ukraine

Facility Name

Site UA38007

City

Kiev

ZIP/Postal Code

02232

Country

Ukraine

Facility Name

Site UA38003

City

Kyiv

ZIP/Postal Code

02660

Country

Ukraine

Facility Name

Site UA38010

City

Kyiv

ZIP/Postal Code

04053

Country

Ukraine

Facility Name

Site UA38008

City

Zaporizhzhya

ZIP/Postal Code

69600

Country

Ukraine

Facility Name

Site GB44001

City

Sheffield

State/Province

South Yorkshire

ZIP/Postal Code

S10 2JF

Country

United Kingdom

Facility Name

Site GB44006

City

Plymouth

ZIP/Postal Code

PL6 8DH

Country

United Kingdom

Facility Name

Site GB44009

City

Watford

ZIP/Postal Code

WD25 7NL

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

IPD Sharing Time Frame

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

IPD Sharing Access Criteria

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/

Citations:

PubMed Identifier

29866467

Citation

Gratzke C, van Maanen R, Chapple C, Abrams P, Herschorn S, Robinson D, Ridder A, Stoelzel M, Paireddy A, Yoon SJ, Al-Shukri S, Rechberger T, Mueller ER. Long-term Safety and Efficacy of Mirabegron and Solifenacin in Combination Compared with Monotherapy in Patients with Overactive Bladder: A Randomised, Multicentre Phase 3 Study (SYNERGY II). Eur Urol. 2018 Oct;74(4):501-509. doi: 10.1016/j.eururo.2018.05.005. Epub 2018 Jun 1.

Results Reference

derived

Links:

URL

https://astellasclinicalstudyresults.com/study.aspx?ID=246

Description

Link to results on the Astellas Clinical Study Results website

Learn more about this trial

A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder

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A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder (SYNERGY II)

Urinary Bladder Overactive, Overactive Bladder, Urgency Incontinence

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

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