The purpose of this study was to see if adding a new type of medication recently approved to treat overactive bladder (mirabegron) to an antimuscarinic treatment (solifenacin) would be more effective in controlling incontinence than when using the antimuscarinic treatment alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
2,174
Mirabegron was supplied as the marketed formulation in the 25 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.
Mirabegron was supplied as the marketed formulation in the 50 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.
Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.
Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the Full Analysis Set (FAS) which comprised of all the Randomized Analysis Set's (RAS) participants who met the following criteria: took at least 1 dose of double-blind study drug after randomization, reported at least 1 micturition in the baseline diary \& at least 1 micturition postbaseline \& reported at least 1 incontinence episode in the baseline diary. For participants who withdrew before EoT (week 12) and have no measurement available for that diary period, the Last Observation Carried Forward (LOCF) value during the double-blind study period was used as EoT value to derive the primary variable.
Time frame: Baseline and end of treatment (up to 12 weeks)
Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours
The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in Mean Number of Micturitions Per 24 Hours
The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period (excluding incontinence only episodes).
Time frame: Baseline and weeks 4, 8 & 12
Number of Incontinence Episodes Reported During the 3-Day Diary
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Solifenacin was provided as the marketed formulation in the 10 mg strength. Medication was taken orally with a glass of water, with or without food.
Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Genova Clinical Research
Tucson, Arizona, United States
Associated Pharmaceutical Research Center, Inc.
Buena Park, California, United States
The American Institute of Research
Los Angeles, California, United States
Bayview Research Group
Valley Village, California, United States
Meridien Research
Brooksville, Florida, United States
Innovative Research of West FL
Clearwater, Florida, United States
Best Quality Research Inc.
Hialeah, Florida, United States
Palmetto Professional Research
Hialeah, Florida, United States
Urology Center of Central Florida
Kissimmee, Florida, United States
Meridien Research
Tampa, Florida, United States
...and 209 more locations
The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3-day micturition diary period.
Time frame: Weeks 4, 8 and 12
Change From Baseline in Mean Volume Voided (MVV) Per Micturition
MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3-day micturition diary period. MVV per micturition was calculated as the sum of each volume voided for each record with volume voided \> 0 on valid diary days divided by the total number of records with a volume voided \> 0 on valid diary days during the 3-day micturition diary period.
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline to EoT in Corrected Micturition Frequency (CMF)
CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT.
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours
UI was defined as the complaint of involuntary urine leakage accompanied by or immediately preceded by urgency. UI was measured using the Patient Perception of Intensity of Urgency Scale (PPIUS), a patient reported outcome validated 5-point categorical scale rating the degree of associated urinary urgency severity (0=No urgency, I felt no need to empty my bladder, but did so for other reasons. 1=Mild, I could postpone voiding as long as necessary, without fear of wetting myself. 2= Moderate, I could postpone voiding for a short while, without fear of wetting myself. 3=Severe, I could not postpone voiding, but had to rush to the toilet in order not to wet myself. 4=Urgency incontinence, I leaked before arriving to the toilet). One urgency incontinence episode was counted for each record of the diary in which the following occurred: incontinence episode or 'both' was recorded \& severity of urinary urgency recorded was 3 or 4.
Time frame: Baseline and weeks 4, 8 & 12
Number of UI Episodes Reported During the 3-Day Diary
Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3-day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted.
Time frame: Weeks 4, 8 and 12
Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3-day micturition diary period. Measured using the PPIUS scale. This was calculated using the sum of each record with an urgency episode (severity of 3 or 4) recorded on a valid diary day divided by the number of valid diary days during the 3-day micturition diary period.
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in Mean Number of Pads Per 24 Hours
The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3-day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.
Time frame: Baseline and weeks 4, 8 & 12
Number of Pads Used During the 3-Day Diary
The number of pads used was defined as the number of times a participant recorded a new pad used during the 3-day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted.
Time frame: Weeks 4, 8 and 12
Change From Baseline in Mean Number of Nocturia Episodes
Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3-day diary period, divided by the number of valid diary days during the diary period. Night time episode of incontinence only was not considered a nocturia episode. Nocturia episodes were counted for each micturition record which occurred between the date/time of going to bed with intention to sleep and the date/time of getting up with intention to stay awake on a valid diary day \& which was accompanied by a sleep interruption. Nocturia only determined for those who were not night-shift workers.
Time frame: Baseline and weeks 4, 8 & 12
Number of Nocturia Episodes Reported Over 3-Day Diary
The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3-day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3-day micturition diary period.
Time frame: Weeks 4, 8 and 12
Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility
The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time frame: Baseline and EoT (up to 12 weeks)
Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care
The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time frame: Baseline and EoT (up to 12 weeks)
Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities
The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time frame: Baseline and EoT (up to 12 weeks)
Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort
The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time frame: Baseline and EoT (up to 12 weeks)
Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression
The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in OAB-q HRQL Subscale Score: Coping
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in OAB-q HRQL Subscale Score: Concern
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in OAB-q HRQL Subscale Score: Sleep
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score
The TS-VAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely).
Time frame: Baseline and weeks 4, 8 & 12
Change From Baseline in Patient Perception Bladder Control (PPBC) Score
The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. PPBC score: 1-no problem, 2- some very minor problems, 3-some minor problems, 4-moderate problems, 5-severe problems, 6-many severe problems.
Time frame: Baseline and weeks 4, 8 & 12
Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)
The PGIC was a 2-part questionnaire, assessing both the change in the participant's overall condition (Patient Impression in General Health (PIBS)) and change in bladder condition since the start of the study (Patient Impression in General Health (PIGH)) (from very much worse to very much improved). The CGIC was a single questionnaire assessing the participant's change in bladder condition since the beginning of the study (Clinician Impression in Bladder Symptoms (CIBS)).
Time frame: End of treatment (up to 12 weeks)
Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 Hours
Incontinence was defined as any involuntary leakage of urine.
Time frame: Weeks 4, 8 and 12
Percentage of Participants With Zero Incontinence Episodes Postbaseline
Incontinence was defined as any involuntary leakage of urine.
Time frame: Weeks 4, 8 and 12
Percentage of Participants With a Mean of at Least 8 Micturitions Per 24 Hours at Baseline and Less Than 8 Micturitions Per 24 Hours Postbaseline
Micturitions were defined as voluntary urinations (excluding incontinence only episodes).
Time frame: Weeks 4, 8 and 12
Percentage of Participants With at Least a 10-Point Improvement From Baseline in OAB-q Symptom Bother Score
The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity).
Time frame: Weeks 4, 8 and 12
Percentage of Participants With at Least a 10-Point Improvement From Baseline in HRQL Total Score
HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time frame: Weeks 4, 8 and 12
Percentage of Participants With at Least a 1-Point Improvement From Baseline in PPBC
The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition.
Time frame: Weeks 4, 8 and 12
Percentage of Participants With Major (at Least 2-Point) Improvement From Baseline in PPBC
The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition.
Time frame: Weeks 4, 8 and 12
Number of Participants With Adverse Events (AEs)
AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures \& which does not necessarily have a causal relationship with this treatment. Treatment-Emergent Adverse Event (TEAE) referred to an adverse event which started or worsened in the period from first double-blind medication intake until 30 days after the last double-blind medication intake.
Time frame: From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)
Change From Baseline in Post Void Residual (PVR) Volume
PVR Volume was assessed by bladder scan.
Time frame: Baseline and weeks 4, 8 & 12