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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)

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ClinicalTrials.gov Identifier: NCT02045862
Recruitment Status : Completed
First Posted : January 27, 2014
Results First Posted : June 6, 2018
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

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.

Condition or disease Intervention/treatment Phase
Urinary Bladder Overactive Overactive Bladder Urgency Incontinence Urinary Bladder Diseases\Urologic Diseases Drug: Solifenacin succinate Drug: Mirabegron Drug: Placebo to match solifenacin Drug: Placebo to match mirabegron Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1829 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 17, 2014
Actual Primary Completion Date : September 8, 2016
Actual Study Completion Date : September 8, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Mirabegron 50 mg
Participants received mirabegron 50 mg once a day for 52 weeks.
Drug: Mirabegron
Participants received mirabegron 50 mg orally once a day at the same time each day.
Other Names:
  • Myrbetriq
  • YM178
  • Betmiga
  • Betanis

Drug: Placebo to match solifenacin
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.

Active Comparator: Solifenacin 5 mg
Participants received solifenacin 5 mg once a day for 52 weeks.
Drug: Solifenacin succinate
Participants received solifenacin 5 mg orally once a day at the same time each day.
Other Names:
  • Vesicare
  • Vesitrim
  • YM905
  • Vesikur

Drug: Placebo to match mirabegron
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.

Experimental: Solifenacin 5 mg + Mirabegron 50 mg
Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Drug: Solifenacin succinate
Participants received solifenacin 5 mg orally once a day at the same time each day.
Other Names:
  • Vesicare
  • Vesitrim
  • YM905
  • Vesikur

Drug: Mirabegron
Participants received mirabegron 50 mg orally once a day at the same time each day.
Other Names:
  • Myrbetriq
  • YM178
  • Betmiga
  • Betanis




Primary Outcome Measures :
  1. 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 56 weeks) ]
    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).

  2. Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and Week 52 ]
    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 the baseline and week 52 clinic visits.

  3. Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours [ Time Frame: Baseline and Week 52 ]
    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 :
  1. Change From Baseline to EoT in Mean Volume Voided Per Micturition [ Time Frame: Baseline and Week 52 ]
    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.

  2. Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score [ Time Frame: Baseline and Week 52 ]
    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.

  3. Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS) [ Time Frame: Baseline and Week 52 ]
    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.

  4. Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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 the baseline and prior to each visit.

  5. Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  6. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  7. Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  8. Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  9. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  10. Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  11. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  12. Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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 prior to each visit.

  13. 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) [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  14. Change From Baseline to EoT in Corrected Micturition Frequency [ Time Frame: Baseline and Month 12 ]
    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.

  15. Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition [ Time Frame: Baseline and Months 3, 6, 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 prior to each visit.

  16. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  17. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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."

  18. Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  19. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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

  20. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  21. Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  22. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  23. Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score [ Time Frame: Baseline and Months 1, 3, 6, 9, 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 indicated an improvement.

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

  25. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  26. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  27. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  28. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  29. Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS [ Time Frame: Baseline and Months 1, 3, 6, 9, 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 indicated improvement.

  30. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC) [ Time Frame: Baseline and Months 1, 3, 6, 9, 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.

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

  32. Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT [ Time Frame: Month 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).

  33. Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility [ Time Frame: Baseline and 12 Months ]
    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).

  34. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care [ Time Frame: Baseline and Month 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).

  35. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities [ Time Frame: Baseline and Month 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).

  36. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort [ Time Frame: Baseline and Month 12 ]
    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).

  37. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression [ Time Frame: Baseline and Month 12 ]
    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).

  38. 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 [ Time Frame: Baseline and Months 6,12 ]
    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 indicated improvement.

  39. Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working [ Time Frame: Baseline and Months 6, 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 indicated improvement.

  40. Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment [ Time Frame: Baseline and Months 6, 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 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.

  41. Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment [ Time Frame: Baseline and Months 6, 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 indicated improvement.

  42. 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 [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  43. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  44. Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  45. Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  46. 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 [ Time Frame: Months 1, 3, 6, 9, 12 ]
    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.

  47. Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  48. Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT [ Time Frame: Baseline and Months 1, 3, 6, 9, 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.

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

  50. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  51. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  52. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  53. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  54. 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 [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    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.

  55. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume [ Time Frame: Baseline and Months 1, 3, 6, 9, 12 ]
    PVR volume was assessed by ultrasonography or a bladder scanner.



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, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT02045862


  Show 251 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Medical Director Astellas Pharma Europe B.V.

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT02045862     History of Changes
Other Study ID Numbers: 178-CL-102
2012-005736-29 ( EudraCT Number )
First Posted: January 27, 2014    Key Record Dates
Results First Posted: June 6, 2018
Last Update Posted: September 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.
URL: https://www.clinicalstudydatarequest.com/

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

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