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This is a Multinational Study Comparing the Efficacy and Safety of Two Medicines , Solifenacin Succinate and Mirabegron Taken Together, or Separately, or a Mock Treatment (Placebo) in Subjects With Symptoms of Overactive Bladder (SYNERGY)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01972841
First Posted: October 31, 2013
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
  Purpose
The purpose of this study is to examine how well two medicines (solifenacin succinate and mirabegron) combined work compared to each medicine alone in the treatment of bladder problems.

Condition Intervention Phase
Urinary Bladder Overactive Urinary Bladder Diseases\Urologic Diseases Overactive Bladder Urgency Incontinence Drug: Solifenacin succinate Drug: Mirabegron Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multi-center Study to Evaluate the Efficacy, Safety and Tolerability of Combinations of Solifenacin Succinate and Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in the Treatment of Overactive Bladder

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):

Primary Outcome Measures:
  • Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes per 24 Hours [ Time Frame: Baseline and Week 12 ]
    An incontinence episode is 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 per day on valid diary days during the 7-day micturition diary period.

  • Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours [ Time Frame: Baseline and Week 12 ]
    A micturition is defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.


Secondary Outcome Measures:
  • Change from Baseline to EoT in Mean Volume Voided per Micturition [ Time Frame: Baseline and Week 12 ]
    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 OAB Questionnaire (OAB-q) Symptom Bother Score [ Time Frame: Baseline and Week 12 ]
    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 indicates an improvement.

  • Change from baseline in Subject assessment of Treatment Satisfaction-Visual Change from Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS) [ Time Frame: Baseline and Week 12 ]
    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 indicates improvement.

  • Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8, 12 ]
    The number of incontinence episodes is the number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8 and 12 in Mean Volume Voided per Micturition [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to EoT in Corrected Micturition Frequency [ Time Frame: Baseline and Week 12 ]
    Corrected micturition frequency is 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.

  • Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EOT [ Time Frame: Weeks 4, 8 and 12 ]
    An urgency incontinence episode is defined as the involuntary leakage of urine accompanied by or immediately proceeded by urgency. The number of urgency incontinence episodes is number of times a participant records an urgency incontinence episode during the 7-day micturition diary period prior to each visit.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
    The mean number of urgency incontinence episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
    An urgency episode is a complaint of a sudden, compelling desire to pass urine, which is difficult to defer; it is recorded when a micturition or incontinence episode is recorded and the severity of urinary urgency recorded is 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.

  • Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    A nocturia episode is 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 patients gets up in the morning with the intention to stay awake). The number of nocturia episodes is the number of times a participant records a nocturia episode during the 7-day micturition diary period prior to each visit.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
    The mean number of nocturia episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.

  • Number of Pads Used at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The number of pads used is the number of times a participant records a new pad used during the 7-day micturition diary period prior to each visit.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used per 24 Hours [ Time Frame: Baseline and Weeks 4, 8, 12 ]
    The mean number of pads used was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.

  • Number of Incontinence-Free Days at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The number of incontinence-free days is the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded.

  • Number of Days with < 8 Micturitions at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The number of days with < 8 micturitions is the number of valid diary days during the 7-day micturition diary period with less than 8 micturitions per day.

  • Number of Incontinence-Free Days with < 8 micturitions per day at Weeks 4, 8 and 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The number of incontinence-free days with < 8 micturitions per day is 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 in Patient Perception of Bladder Condition Questionnaire (PPBC) at Weeks 4, 8 and 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    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 Weeks 4, 8 and 12 in the OAB-q Symptom Bother Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Weeks 4, 8, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL) Total Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), 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 indicates an improvement.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Coping [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), 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 indicates an improvement.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Concern [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), 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 indicates an improvement.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Sleep [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), 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 indicates an improvement.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Social [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), 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 indicates an improvement.

  • Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT [ Time Frame: Week 12 ]
    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).

  • PGIC Scale: Impression in General Health at Week 12 and EoT [ Time Frame: Week 12 ]
    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).

  • Change from Baseline to EoT in European Quality of Life in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility [ Time Frame: Baseline and Week 12 ]
    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).

  • Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care [ Time Frame: Baseline and Week 12 ]
    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).

  • Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities [ Time Frame: Baseline and Week 12 ]
    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).

  • Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort [ Time Frame: Baseline and Week 12 ]
    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).

  • Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression [ Time Frame: Baseline and Week 12 ]
    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).

  • Change from Baseline to Week 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Time Work Missed [ Time Frame: Baseline and Week 12 ]
    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 indicates improvement.

  • Change from Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Impairment While Working [ Time Frame: Baseline and Week 12 ]
    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 indicates improvement.

  • Change from Baseline to Weeks 4, 8 and 12 in the TS-VAS [ Time Frame: Baseline and Weeks 4, 8, 12 ]
  • Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 3 Diary Days at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 3 days prior to weeks 4, 8, 12 and EoT.

  • Percentage of Participants with ≥ 10 Points Improvement from Baseline in the OAB-q Symptom Bother Score at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).

  • Percentage of Participants with ≥ 10 Points Improvement from Baseline in HRQL Total Score at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).

  • Percentage of Participants with 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with ≥ 50% decrease from baseline in mean number of incontinence episodes per 24 hours at each time point (weeks 4, 8, 12 and EoT).

  • Percentage of Participants with Micturition Frequency Normalization at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with micturition frequency normalization is defined as any participant who had ≥ 8 micturitions/24 hours at baseline and < 8 micturitions/24 h postbaseline at weeks 4, 8, 12 and EoT.

  • Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 7 Diary Days at Weeks 4, 8, 12 and EoT [ Time Frame: Weeks 4, 8 and 12 ]
    The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 7 days prior to weeks 4, 8, 12 and EoT.

  • Percentage of Participants with ≥ 1 Point Improvement from Baseline in PPBC at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.

  • Percentage of Participants with Major (≥ 2 points) Improvement from Baseline in PPBC at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants with a major (≥ 2 points) improvement from baseline in PPBC at weeks 4, 8, 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 Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score at weeks 4, 8, 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 HRQL Total Score) at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q HRQL total score at weeks 4, 8, 12 and EoT.

  • 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 Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.

  • Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, at least 10 Points Improvement on OAB-q Symptom Bother Scale and at least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.

  • Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, at least 10 Points Improvement on OAB-q HRQL Total Score and at least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the HRQL total score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.

  • Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 16 weeks) ]
    A TEAE refers to an adverse event (AE; defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment) which started or worsened in the period from first double-blind medication intake until 14 days after the last double-blind medication intake. Serious TEAEs with a start date reported until 30 days after the last double-blind medication intake were also summarized as TEAEs, and also included serious TEAEs upgraded by the sponsor based on review of the sponsor's list of Always Serious terms if any upgrade was done. Drug-related TEAEs may be possible or probable, as assessed by the investigator, or records where relationship is missing.

  • Change from Baseline to Weeks 4, 8, 12 and EoT in Postvoid Residual (PVR) Volume [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
    PVR volume was assessed by ultrasonography or a bladder scanner.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean 24 hours (h), Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP) [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Pulse Rate [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean SBP 4 to 6 Hours Postdose [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax (time to maximum concentration) window of mirabegron and solifenacin was from 4-6 hours postdose.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean DBP 4 to 6 Hours Postdose [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax (time to maximum concentration) window of mirabegron and solifenacin was from 4-6 hours postdose.

  • Change from Baseline to Weeks 4, 12 and EoT in Mean Pulse Rate 4 to 6 Hours Postdose [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax (time to maximum concentration) window of mirabegron and solifenacin was from 4-6 hours postdose.

  • Maximum 1-hour Change from Time-matched Baseline in SBP at Weeks 4, 12 and EoT [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Maximum 1-hour Change from Time-matched Baseline in DBP at Weeks 4, 12 and EoT [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Maximum 1-hour Change from Time-matched Baseline in Pulse Rate at Weeks 4, 12 and EoT [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.

  • Change from Baseline to Weeks 4, 12 and EoT in SBP Peak/Trough Difference [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference is defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.

  • Change from Baseline to Weeks 4, 12 and EoT in DBP Peak/Trough Difference [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference is defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.

  • Change from Baseline to Weeks 4, 12 and EoT in Pulse Rate Peak/Trough Difference [ Time Frame: Baseline and Weeks 4 and 12 ]
    Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference is defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.


Enrollment: 3527
Actual Study Start Date: November 5, 2013
Study Completion Date: October 22, 2015
Primary Completion Date: October 22, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: Solifenacin 5 mg + Mirabegron 25 mg
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Drug: Solifenacin succinate
Oral tablet
Other Names:
  • Vesikur
  • Vesitrim
  • YM905
  • Vesicare
Drug: Mirabegron
Oral tablet
Other Names:
  • YM178
  • Betmiga
  • Betanis
  • Myrbetriq
Experimental: 2: Solifenacin 5 mg + Mirabegron 50 mg
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Drug: Solifenacin succinate
Oral tablet
Other Names:
  • Vesikur
  • Vesitrim
  • YM905
  • Vesicare
Drug: Mirabegron
Oral tablet
Other Names:
  • YM178
  • Betmiga
  • Betanis
  • Myrbetriq
Placebo Comparator: 3: Placebo
Participants who received matching placebo once a day for 12 weeks.
Drug: Placebo
Oral tablet
Active Comparator: 4: Solifenacin 5 mg
Participants who received solifenacin 5 mg once a day for 12 weeks.
Drug: Solifenacin succinate
Oral tablet
Other Names:
  • Vesikur
  • Vesitrim
  • YM905
  • Vesicare
Active Comparator: 5:Mirabegron 25 mg
Participants who received mirabegron 25 mg once a day for 12 weeks.
Drug: Mirabegron
Oral tablet
Other Names:
  • YM178
  • Betmiga
  • Betanis
  • Myrbetriq
Active Comparator: 6: Mirabegron 50 mg
Participants who received mirabegron 50 mg once a day for 12 weeks.
Drug: Mirabegron
Oral tablet
Other Names:
  • YM178
  • Betmiga
  • Betanis
  • Myrbetriq

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is 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;
  • Subject has symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months;

Exclusion Criteria:

  • Subject has significant PVR volume (> 150 mL);
  • Subject has a neurological cause for detrusor overactivity (e.g. neurogenic bladder, diabetic neuropathy with autonomic component or bladder involvement, or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component can be inferred when autonomic functions are affected, including heart rate, blood pressure, perspiration and digestion.
  • Subject has an indwelling catheter or practices intermittent self catheterization.
  • Subject has chronic inflammation such as bladder pain syndrome /interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.
  • Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
  • Subject has moderate to severe hepatic impairment
  • Subject has severe renal impairment
  • Subject has a clinically significant abnormal ECG
  • Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
  • Subject has an average QTcF interval > 450 ms for males or > 470 ms for females based on the triplicate ECGs completed at Screening or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
  • Subject has severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01972841


  Show 435 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Medical Director Astellas Pharma Europe B.V.
  More Information

Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT01972841     History of Changes
Other Study ID Numbers: 178-CL-101
2012-005735-91 ( EudraCT Number )
U1111-1153-9095 ( Other Identifier: World Health Organization )
First Submitted: October 25, 2013
First Posted: October 31, 2013
Last Update Posted: October 3, 2017
Last Verified: September 2017

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Combination Therapy
Mirabegron
Overactive Bladder
Urgency
Urinary Incontinence
Nocturia
Solifenacin Succinate

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urologic Diseases
Urinary Bladder Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Solifenacin Succinate
Mirabegron
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents