BESIDE: A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)
Sponsor
Astellas Pharma Europe Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01908829
Collaborator
(none)
2,174
219
3
16.5
9.9
0.6
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2174 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Multi-Centre Study to Evaluate the Efficacy and Safety of Adding Mirabegron to Solifenacin in Incontinent OAB Subjects Who Have Received Solifenacin for 4 Weeks and Warrant Additional Relief for Their OAB Symptoms
Actual Study Start Date
:
Jul 10, 2013
Actual Primary Completion Date
:
Nov 24, 2014
Actual Study Completion Date
:
Nov 25, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Combination (solifenacin + mirabegron) Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. |
Drug: mirabegron 25 mg
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.
Other Names:
Drug: mirabegron 50 mg
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.
Other Names:
Drug: solifenacin 5 mg
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.
Other Names:
Drug: solifenacin 10 mg matching placebo
Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
|
| Active Comparator: Solifenacin 5 mg Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period |
Drug: solifenacin 5 mg
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.
Other Names:
Drug: mirabegron 25 mg matching placebo
Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Drug: mirabegron 50 mg matching placebo
Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Drug: solifenacin 10 mg matching placebo
Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
|
| Active Comparator: Solifenacin 10 mg Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
Drug: solifenacin 10 mg
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.
Other Names:
Drug: mirabegron 25 mg matching placebo
Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Drug: mirabegron 50 mg matching placebo
Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Drug: solifenacin 5 mg matching placebo
Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and end of treatment (up to 12 weeks)]
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.
Secondary Outcome Measures
- Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and weeks 4, 8 & 12]
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.
- Change From Baseline in Mean Number of Micturitions Per 24 Hours [Baseline and weeks 4, 8 & 12]
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).
- Number of Incontinence Episodes Reported During the 3-Day Diary [Weeks 4, 8 and 12]
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.
- Change From Baseline in Mean Volume Voided (MVV) Per Micturition [Baseline and weeks 4, 8 & 12]
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.
- Change From Baseline to EoT in Corrected Micturition Frequency (CMF) [Baseline and EoT (up to 12 weeks)]
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.
- Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours [Baseline and weeks 4, 8 & 12]
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.
- Number of UI Episodes Reported During the 3-Day Diary [Weeks 4, 8 and 12]
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.
- Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours [Baseline and weeks 4, 8 & 12]
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.
- Change From Baseline in Mean Number of Pads Per 24 Hours [Baseline and weeks 4, 8 & 12]
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.
- Number of Pads Used During the 3-Day Diary [Weeks 4, 8 and 12]
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.
- Change From Baseline in Mean Number of Nocturia Episodes [Baseline and weeks 4, 8 & 12]
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.
- Number of Nocturia Episodes Reported Over 3-Day Diary [Weeks 4, 8 and 12]
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.
- Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility [Baseline and EoT (up to 12 weeks)]
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.
- Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care [Baseline and EoT (up to 12 weeks)]
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.
- Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities [Baseline and EoT (up to 12 weeks)]
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.
- Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort [Baseline and EoT (up to 12 weeks)]
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.
- Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression [Baseline and EoT (up to 12 weeks)]
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.
- Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in OAB-q HRQL Subscale Score: Coping [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in OAB-q HRQL Subscale Score: Concern [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in OAB-q HRQL Subscale Score: Sleep [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction [Baseline and weeks 4, 8 & 12]
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).
- Change From Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score [Baseline and weeks 4, 8 & 12]
The TS-VAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely).
- Change From Baseline in Patient Perception Bladder Control (PPBC) Score [Baseline and weeks 4, 8 & 12]
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.
- Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC) [End of treatment (up to 12 weeks)]
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)).
- Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 Hours [Weeks 4, 8 and 12]
Incontinence was defined as any involuntary leakage of urine.
- Percentage of Participants With Zero Incontinence Episodes Postbaseline [Weeks 4, 8 and 12]
Incontinence was defined as any involuntary leakage of urine.
- 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 [Weeks 4, 8 and 12]
Micturitions were defined as voluntary urinations (excluding incontinence only episodes).
- Percentage of Participants With at Least a 10-Point Improvement From Baseline in OAB-q Symptom Bother Score [Weeks 4, 8 and 12]
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).
- Percentage of Participants With at Least a 10-Point Improvement From Baseline in HRQL Total Score [Weeks 4, 8 and 12]
HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
- Percentage of Participants With at Least a 1-Point Improvement From Baseline in PPBC [Weeks 4, 8 and 12]
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.
- Percentage of Participants With Major (at Least 2-Point) Improvement From Baseline in PPBC [Weeks 4, 8 and 12]
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.
- Number of Participants With Adverse Events (AEs) [From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)]
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.
- Change From Baseline in Post Void Residual (PVR) Volume [Baseline and weeks 4, 8 & 12]
PVR Volume was assessed by bladder scan.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Main Inclusion at Screening:
-
Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence) for >= 3 months prior to the screening visit
-
Subject is willing and able to complete the micturition diary and questionnaires correctly, including collection and measurement of urine output for 3 days prior to each visit;
-
Subject has symptoms of "wet" OAB (urinary frequency and urgency with incontinence or mixed incontinence with predominant urgency incontinence), and reports an average of at least 2 incontinence episodes per day.
- Main Inclusion at Run-in (Visit 2):
-
Subject experiences on average at least 1 episode of urgency (grade 3 or 4) with or without incontinence per 24-hour period during the 3-day micturition diary period.
-
Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
-
Subject experiences on average at least 8 micturitions (excluding incontinence episodes) per 24-hour period during the 3-day micturition diary period.
- Main Inclusion at Randomization (Visit 3):
- Subject experiences at least 1 incontinence episode during the 3-day micturition diary period and wishes to increase their treatment for OAB symptoms.
Exclusion Criteria:
- Main Exclusion at Screening:
-
Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
-
Subject has significant Post-void residual (PVR) volume (PVR > 150 ml).
-
Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
-
Subject has an indwelling catheter or practices intermittent self catheterization.
-
Subject has evidence of a UTI.
-
Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs
-
Subject has moderate to severe hepatic impairment
-
Subject has severe renal impairment or End Stage Renal disease
-
Subject has a clinically significant abnormal Electrocardiogram (ECG)
-
Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
-
Subject has a QTcF interval > 450 ms for males or > 470 ms for females or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
-
Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
-
Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
- Main Exclusion at Randomization (visit 3):
-
Subject has achieved 100% continence from Visit 2 to Visit 3 (no incontinence episodes are recorded in the 3 day diary administered for 3 days prior to Visit 3).
-
Subject does not desire an increase in study medication.
-
Subject has an average total daily urine volume > 3000ml as recorded in the micturition diary.
-
Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
-
Subject has a clinically significant abnormal ECG
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Genova Clinical Research | Tucson | Arizona | United States | 85704 |
| 2 | Associated Pharmaceutical Research Center, Inc. | Buena Park | California | United States | 90620 |
| 3 | The American Institute of Research | Los Angeles | California | United States | 90017 |
| 4 | Bayview Research Group | Valley Village | California | United States | 91607 |
| 5 | Meridien Research | Brooksville | Florida | United States | 33016 |
| 6 | Innovative Research of West FL | Clearwater | Florida | United States | 33756 |
| 7 | Best Quality Research Inc. | Hialeah | Florida | United States | 33016 |
| 8 | Palmetto Professional Research | Hialeah | Florida | United States | 33016 |
| 9 | Urology Center of Central Florida | Kissimmee | Florida | United States | 34741 |
| 10 | Meridien Research | Tampa | Florida | United States | 33606 |
| 11 | Stedman Clinical Trials | Tampa | Florida | United States | 33613 |
| 12 | Private Practice | West Palm Beach | Florida | United States | 33407 |
| 13 | Meridian Clinical Research, LLC | Savannah | Georgia | United States | 31406 |
| 14 | Herman Clinical Research | Suwanee | Georgia | United States | 30024 |
| 15 | North Idaho Urology | Coeur d'Alene | Idaho | United States | 83814 |
| 16 | First Urology, PSC | Jeffersonville | Indiana | United States | 47130 |
| 17 | Deaconess Gateway Health Center | Newburgh | Indiana | United States | 47630 |
| 18 | MedStar Health Research Institute | Hyattsville | Maryland | United States | 20782 |
| 19 | Bay State Clinical Trials, Inc. | Watertown | Massachusetts | United States | 02472 |
| 20 | Beyer Research | Kalamazoo | Michigan | United States | 49009 |
| 21 | Quality Clinical Research | Omaha | Nebraska | United States | 68114 |
| 22 | Albuquerque Clinical Trials, Inc. | Albuquerque | New Mexico | United States | 87102 |
| 23 | Brooklyn Urology Research Group | Brooklyn | New York | United States | 11215 |
| 24 | Advanced Urology Centers of New York | Garden City | New York | United States | 11530 |
| 25 | Premier Medical Group of the Hudson Valley PC | Kingston | New York | United States | 12401 |
| 26 | Premier Medical Group of the Hudson Valley PC | Poughkeepsie | New York | United States | 12601 |
| 27 | PMG Research of Raleigh, dba PMG Research of Cary | Cary | North Carolina | United States | 27518 |
| 28 | Alliance Urology Specialists | Greensboro | North Carolina | United States | 27403 |
| 29 | Wake Research Associates LLC | Raleigh | North Carolina | United States | 27612 |
| 30 | PMG Research of Winston-Salem, LLC | Winston-Salem | North Carolina | United States | 27103 |
| 31 | The Urology Group | Cincinnati | Ohio | United States | 45212 |
| 32 | Providence Health Partners | Dayton | Ohio | United States | 45439 |
| 33 | The Clinical Trial Center | Jenkintown | Pennsylvania | United States | 19046 |
| 34 | Health Concepts | Rapid City | South Dakota | United States | 57702 |
| 35 | Jean Brown Research | Salt Lake City | Utah | United States | 84124 |
| 36 | Alexandria Clinical Research | Alexandria | Virginia | United States | 22304 |
| 37 | Site: 37402 | Yerevan | Armenia | ||
| 38 | Site: 37403 | Yerevan | Armenia | ||
| 39 | Site: 37405 | Yerevan | Armenia | ||
| 40 | Site: 61006 | Adelaide | Australia | ||
| 41 | Site: 61001 | Kogarah, Sydney | Australia | ||
| 42 | Site: 61016 | Victoria | Australia | ||
| 43 | Site: 43008 | Graz | Austria | ||
| 44 | Site: 43001 | Innsbruck | Austria | ||
| 45 | Site: 43006 | Innsbruck | Austria | ||
| 46 | Site: 43007 | Linz | Austria | ||
| 47 | Site: 43002 | Vienna | Austria | ||
| 48 | Site: 43004 | Vienna | Austria | ||
| 49 | Site: 43005 | Vienna | Austria | ||
| 50 | Site: 43010 | Vienna | Austria | ||
| 51 | Site: 43011 | Vienna | Austria | ||
| 52 | Site: 43012 | Vienna | Austria | ||
| 53 | Site: 43003 | Wels | Austria | ||
| 54 | Site: 32007 | Anderlecht | Belgium | ||
| 55 | Site: 32013 | Deurne | Belgium | ||
| 56 | Site: 32009 | Edegem | Belgium | ||
| 57 | Site: 32003 | Gent | Belgium | ||
| 58 | Site: 32005 | Gent | Belgium | ||
| 59 | Site: 32015 | Kortrijk | Belgium | ||
| 60 | Site: 32008 | Liege | Belgium | ||
| 61 | Site: 32014 | Roeselare | Belgium | ||
| 62 | Site: 15001 | Barrie | Canada | ||
| 63 | Site: 15009 | Bathurst | Canada | ||
| 64 | Site: 15006 | Brampton | Canada | ||
| 65 | Site: 15015 | Granby | Canada | ||
| 66 | Site: 15014 | Kelowna | Canada | ||
| 67 | Site: 15007 | Kitchener | Canada | ||
| 68 | Site: 15019 | Sherbrooke | Canada | ||
| 69 | Site: 15012 | Toronto | Canada | ||
| 70 | Site: 15013 | Toronto | Canada | ||
| 71 | Site: 15018 | Victoriaville | Canada | ||
| 72 | Site: 15016 | Victoria | Canada | ||
| 73 | Site: 15047 | Victoria | Canada | ||
| 74 | Site: 42015 | Brno | Czechia | ||
| 75 | Site: 42020 | Melnik | Czechia | ||
| 76 | Site: 42018 | Nachod | Czechia | ||
| 77 | Site: 42004 | Plzen | Czechia | ||
| 78 | Site: 42021 | Plzen | Czechia | ||
| 79 | Site: 42016 | Prague 1 | Czechia | ||
| 80 | Site: 42008 | Prague | Czechia | ||
| 81 | Site: 42017 | Praha 2 | Czechia | ||
| 82 | Site: 42007 | Praha 4 | Czechia | ||
| 83 | Site: 42022 | Praha 4 | Czechia | ||
| 84 | Site: 45008 | Aarhus N | Denmark | ||
| 85 | Site: 45003 | Frederiksberg | Denmark | ||
| 86 | Site: 45009 | Herlev | Denmark | ||
| 87 | Site: 45011 | Odense C | Denmark | ||
| 88 | Site: 35804 | Helsinki (hus) | Finland | ||
| 89 | Site: 35805 | Tampere | Finland | ||
| 90 | Site: 33018 | Bordeaux Cedex | France | ||
| 91 | Site: 33017 | Marseille | France | ||
| 92 | Site: 99502 | T'bilisi | Georgia | ||
| 93 | Site: 49008 | Bad Ems | Germany | ||
| 94 | Site: 49022 | Berlin | Germany | ||
| 95 | Site: 49021 | Hagenow | Germany | ||
| 96 | Site: 49011 | Halle (Saale) | Germany | ||
| 97 | Site: 49004 | Hamburg | Germany | ||
| 98 | Site: 49018 | Henningsdorf | Germany | ||
| 99 | Site: 49009 | Hettstedt | Germany | ||
| 100 | Site: 49017 | Koblenz | Germany | ||
| 101 | Site: 49003 | Lutherstadt Eisleben | Germany | ||
| 102 | Site: 49020 | Reutlingen | Germany | ||
| 103 | Site: 49014 | Sangerhausen | Germany | ||
| 104 | Site: 30001 | Athens | Greece | ||
| 105 | Site: 30005 | Heraklion, Crete | Greece | ||
| 106 | Site: 30002 | Patras | Greece | ||
| 107 | Site: 36003 | Csongrad | Hungary | ||
| 108 | Site: 36011 | Hajduszoboszlo | Hungary | ||
| 109 | Site: 36002 | Nyiregyhaza | Hungary | ||
| 110 | Site: 36008 | Salgotarjan | Hungary | ||
| 111 | Site: 36009 | Szekszard | Hungary | ||
| 112 | Site: 35303 | Cork | Ireland | ||
| 113 | Site: 35301 | Dublin | Ireland | ||
| 114 | Site: 35309 | Dublin | Ireland | ||
| 115 | Site: 35310 | Dublin | Ireland | ||
| 116 | Site: 35306 | Limerick | Ireland | ||
| 117 | Site: 35313 | Mullingar | Ireland | ||
| 118 | Site: 35304 | Tralee | Ireland | ||
| 119 | Site: 35305 | Waterford | Ireland | ||
| 120 | Site: 97201 | Haifa | Israel | ||
| 121 | Site: 97202 | Jerusalem | Israel | ||
| 122 | Site: 97207 | Kfar Saba | Israel | ||
| 123 | Site: 97203 | Petach Tikva | Israel | ||
| 124 | Site: 97205 | Petach Tikva | Israel | ||
| 125 | Site: 97206 | Tel Hashomer | Israel | ||
| 126 | Site: 39007 | Avellino | Italy | ||
| 127 | Site: 39002 | Cantanzaro | Italy | ||
| 128 | Site: 39010 | Firenze | Italy | ||
| 129 | Site: 39006 | Perugia | Italy | ||
| 130 | Site: 39013 | Treviglio (BG) | Italy | ||
| 131 | Site: 39009 | Varese | Italy | ||
| 132 | Site: 96101 | Beirut | Lebanon | ||
| 133 | Site: 31008 | Amsterdam | Netherlands | ||
| 134 | Site: 47005 | Bekkestua | Norway | ||
| 135 | Site: 47002 | Tonsberg | Norway | ||
| 136 | Site: 47003 | Trondheim | Norway | ||
| 137 | Site: 48002 | Kolbuszowa Dolna | Poland | ||
| 138 | Site: 48006 | Krakow | Poland | ||
| 139 | Site: 48010 | Lublin | Poland | ||
| 140 | Site: 48005 | Piaseczno | Poland | ||
| 141 | Site: 48001 | Warszawa | Poland | ||
| 142 | Site: 48008 | Warszawa | Poland | ||
| 143 | Site: 35104 | Lisbon | Portugal | ||
| 144 | Site: 35105 | Lisbon | Portugal | ||
| 145 | Site: 35102 | Matosinhos | Portugal | ||
| 146 | Site: 35103 | Porto | Portugal | ||
| 147 | Site: 35101 | Setubal | Portugal | ||
| 148 | Site: 35106 | Tomar | Portugal | ||
| 149 | Site: 40016 | Bucharest | Romania | ||
| 150 | Site: 40018 | Bucharest | Romania | ||
| 151 | Site: 40012 | Craiova | Romania | ||
| 152 | Site: 40019 | Craiova | Romania | ||
| 153 | Site: 40003 | Judetul Ilfov | Romania | ||
| 154 | Site: 40017 | Oradea | Romania | ||
| 155 | Site: 40020 | Timisoara | Romania | ||
| 156 | Site: 70003 | Moscow | Russian Federation | ||
| 157 | Site: 70004 | Moscow | Russian Federation | ||
| 158 | Site: 70005 | Moscow | Russian Federation | ||
| 159 | Site: 70008 | Moscow | Russian Federation | ||
| 160 | Site: 70010 | Moscow | Russian Federation | ||
| 161 | Site: 70011 | Moscow | Russian Federation | ||
| 162 | Site: 70012 | Moscow | Russian Federation | ||
| 163 | Site: 70024 | Moscow | Russian Federation | ||
| 164 | Site: 70013 | Rostove-on-Don | Russian Federation | ||
| 165 | Site: 70002 | Saint Petersburg | Russian Federation | ||
| 166 | Site: 70006 | Saint Petersburg | Russian Federation | ||
| 167 | Site: 70007 | Saint Petersburg | Russian Federation | ||
| 168 | Site: 70009 | Saint Petersburg | Russian Federation | ||
| 169 | Site: 70025 | Saratov | Russian Federation | ||
| 170 | Site: 42110 | Bratislava | Slovakia | ||
| 171 | Site: 42114 | Kosice | Slovakia | ||
| 172 | Site: 42113 | Michalovce | Slovakia | ||
| 173 | Site: 42111 | Nove Zamky | Slovakia | ||
| 174 | Site: 42112 | Piestany | Slovakia | ||
| 175 | Site: 42108 | Poprad | Slovakia | ||
| 176 | Site: 42109 | Zilina | Slovakia | ||
| 177 | Site: 38601 | Ljubljana | Slovenia | ||
| 178 | Site: 38606 | Maribor | Slovenia | ||
| 179 | Site: 38607 | Maribor | Slovenia | ||
| 180 | Site: 38610 | Ptuj | Slovenia | ||
| 181 | Site: 34012 | Barcelona | Spain | ||
| 182 | Site: 34016 | Bilbao | Spain | ||
| 183 | Site: 34001 | Getafe (Madrid) | Spain | ||
| 184 | Site: 34004 | Madrid | Spain | ||
| 185 | Site: 34015 | Madrid | Spain | ||
| 186 | Site: 34023 | Mendaro | Spain | ||
| 187 | Site: 34021 | Miranda de Ebro | Spain | ||
| 188 | Site: 34018 | San Sebastian de los Reyes | Spain | ||
| 189 | Site: 34013 | San Sebastian | Spain | ||
| 190 | Site: 34007 | Sevilla | Spain | ||
| 191 | Site: 34020 | Sevilla | Spain | ||
| 192 | Site: 34014 | Vigo | Spain | ||
| 193 | Site: 46004 | Halmstad | Sweden | ||
| 194 | Site: 46013 | Lund | Sweden | ||
| 195 | Site: 46014 | Norrtalje | Sweden | ||
| 196 | Site: 46001 | Stockholm | Sweden | ||
| 197 | Site: 46012 | Stockholm | Sweden | ||
| 198 | Site: 46015 | Umea | Sweden | ||
| 199 | Site: 41008 | Baden | Switzerland | ||
| 200 | Site: 41001 | Frauenfeld | Switzerland | ||
| 201 | Site: 90005 | Ankara | Turkey | ||
| 202 | Site: 90008 | Ankara | Turkey | ||
| 203 | Site: 90002 | Izmir | Turkey | ||
| 204 | Site: 90003 | Izmir | Turkey | ||
| 205 | Site: 90007 | Kocaeli | Turkey | ||
| 206 | Site: 90004 | Manisa | Turkey | ||
| 207 | Site: 90006 | Sivas | Turkey | ||
| 208 | Site: 44007 | Bristol | United Kingdom | ||
| 209 | Site: 44012 | Cambridge | United Kingdom | ||
| 210 | Site: 44015 | Cheltenham | United Kingdom | ||
| 211 | Site: 44019 | Coventry | United Kingdom | ||
| 212 | Site: 44009 | Garston | United Kingdom | ||
| 213 | Site: 44016 | Kings Lynn | United Kingdom | ||
| 214 | Site: 44017 | London | United Kingdom | ||
| 215 | Site: 44018 | Northampton | United Kingdom | ||
| 216 | Site: 44010 | Nottingham | United Kingdom | ||
| 217 | Site: 44008 | Plymouth | United Kingdom | ||
| 218 | Site: 44013 | Taunton | United Kingdom | ||
| 219 | Site: 44011 | West Yorkshire | United Kingdom |
Sponsors and Collaborators
- Astellas Pharma Europe Ltd.
Investigators
- Study Director: Clinical Study Manager, Astellas Pharma Europe Ltd.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Astellas Pharma Europe Ltd.
ClinicalTrials.gov Identifier:
NCT01908829
Other Study ID Numbers:
- 905-EC-012
- 2012-005401-41
First Posted:
Jul 26, 2013
Last Update Posted:
Aug 15, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Astellas Pharma Europe Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This multicenter study was conducted at 281 centers globally. Randomization was stratified by sex, age group (< 65, ≥ 65 years), 4-week incontinence episode reduction group (< 50%, ≥ 50%) and geographic region. |
|---|---|
| Pre-assignment Detail | Participants who met the screening inclusion/exclusion criteria went through a two week wash-out period and maintained a micturition diary during that the wash-out period. A total of 3815 participants were screened of which 2401 participants received solifenacin 5 mg run-in medication. A total of 2174 participants were randomized. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Period Title: Overall Study | |||
| STARTED | 727 | 728 | 719 |
| Treated With Double-blind Drug | 725 | 728 | 719 |
| COMPLETED | 678 | 679 | 680 |
| NOT COMPLETED | 49 | 49 | 39 |
Baseline Characteristics
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. | Total of all reporting groups |
| Overall Participants | 727 | 728 | 719 | 2174 |
| Age (Year) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Year] |
58.2
(13.1)
|
56.9
(13.5)
|
57.4
(13.2)
|
57.5
(13.3)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
604
83.1%
|
604
83%
|
600
83.4%
|
1808
83.2%
|
| Male |
123
16.9%
|
124
17%
|
119
16.6%
|
366
16.8%
|
Outcome Measures
| Title | Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of the FAS. LOCF was used for EoT. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 706 | 704 | 697 |
| Least Squares Mean (Standard Error) [incontinence episodes] |
-1.8
(0.08)
|
-1.53
(0.08)
|
-1.67
(0.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P values for pairwise comparisons were from the stratified rank ANCOVA model. P < 0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) Means |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-1.24
(0.07)
|
-0.91
(0.07)
|
-1.12
(0.07)
|
| Week 8 |
-1.68
(0.07)
|
-1.29
(0.07)
|
-1.49
(0.07)
|
| Week 12 |
-1.81
(0.08)
|
-1.57
(0.08)
|
-1.67
(0.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.52 to -0.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.39 | |
| Confidence Interval |
(2-Sided) 95% -0.60 to -0.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons are from the stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to -0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Number of Micturitions Per 24 Hours |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-0.95
(0.07)
|
-0.69
(0.07)
|
-0.79
(0.07)
|
| Week 8 |
-1.36
(0.08)
|
-0.94
(0.08)
|
-1.00
(0.08)
|
| Week 12 |
-1.63
(0.08)
|
-1.16
(0.09)
|
-1.11
(0.08)
|
| EoT |
-1.59
(0.08)
|
-1.14
(0.08)
|
-1.12
(0.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.010 |
| Comments | P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to -0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.42 | |
| Confidence Interval |
(2-Sided) 95% -0.65 to -0.19 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.47 | |
| Confidence Interval |
(2-Sided) 95% -0.70 to -0.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.45 | |
| Confidence Interval |
(2-Sided) 95% -0.67 to -0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
| Title | Number of Incontinence Episodes Reported During the 3-Day Diary |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
5.81
(0.30)
|
6.68
(0.31)
|
6.41
(0.33)
|
| Week 8 |
4.55
(0.30)
|
5.43
(0.30)
|
5.28
(0.32)
|
| Week 12 |
4.03
(0.29)
|
4.56
(0.28)
|
4.62
(0.31)
|
| EoT |
4.25
(0.29)
|
4.87
(0.28)
|
4.72
(0.31)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 4 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.005 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 0.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 8 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 0.86 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.07 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 12 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.021 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.014 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 0.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Volume Voided (MVV) Per Micturition |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
15.06
(1.55)
|
11.20
(1.55)
|
14.99
(1.55)
|
| Week 8 |
25.21
(1.89)
|
14.02
(1.87)
|
21.08
(1.86)
|
| Week 12 |
29.54
(2.06)
|
17.16
(2.08)
|
20.99
(2.04)
|
| EoT |
28.05
(1.97)
|
16.52
(1.97)
|
20.30
(1.97)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.078 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.86 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 8.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.19 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 11.19 | |
| Confidence Interval |
(2-Sided) 95% 5.98 to 16.40 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.66 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 12.38 | |
| Confidence Interval |
(2-Sided) 95% 6.65 to 18.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.92 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 11.52 | |
| Confidence Interval |
(2-Sided) 95% 6.06 to 16.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.79 |
|
| Estimation Comments | ||
| Title | Change From Baseline to EoT in Corrected Micturition Frequency (CMF) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 706 | 704 | 697 |
| Least Squares Mean (Standard Error) [micturitions] |
-0.96
(0.10)
|
-0.52
(0.10)
|
-0.71
(0.10)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to -0.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one UI episode reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-1.26
(0.07)
|
-0.91
(0.07)
|
-1.14
(0.07)
|
| Week 8 |
-1.70
(0.07)
|
-1.25
(0.07)
|
-1.45
(0.07)
|
| Week 12 |
-1.84
(0.07)
|
-1.58
(0.07)
|
-1.62
(0.07)
|
| EoT |
-1.82
(0.07)
|
-1.54
(0.07)
|
-1.63
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.35 | |
| Confidence Interval |
(2-Sided) 95% -0.54 to -0.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 djusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.45 | |
| Confidence Interval |
(2-Sided) 95% -0.65 to -0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | stratified rank ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to -0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
| Title | Number of UI Episodes Reported During the 3-Day Diary |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one UI episode reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
4.96
(0.27)
|
5.86
(0.29)
|
5.50
(0.30)
|
| Week 8 |
3.55
(0.25)
|
4.76
(0.27)
|
4.50
(0.30)
|
| Week 12 |
3.10
(0.24)
|
3.78
(0.25)
|
3.91
(0.30)
|
| EoT |
3.33
(0.24)
|
4.00
(0.25)
|
3.96
(0.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 4 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.76 to 0.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 8 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.63 to 0.86 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 12 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.038 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.83 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 0.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.022 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one urgency episode reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-1.84
(0.09)
|
-1.39
(0.09)
|
-1.74
(0.10)
|
| Week 8 |
-2.64
(0.10)
|
-2.00
(0.10)
|
-2.29
(0.10)
|
| Week 12 |
-2.97
(0.11)
|
-2.44
(0.11)
|
-2.55
(0.11)
|
| EoT |
-2.95
(0.10)
|
-2.41
(0.10)
|
-2.54
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.45 | |
| Confidence Interval |
(2-Sided) 95% -0.72 to -0.19 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.13 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.64 | |
| Confidence Interval |
(2-Sided) 95% -0.93 to -0.35 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.52 | |
| Confidence Interval |
(2-Sided) 95% -0.82 to -0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.54 | |
| Confidence Interval |
(2-Sided) 95% -0.83 to -0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Number of Pads Per 24 Hours |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with reported use of at least one pad reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-1.12
(0.07)
|
-0.86
(0.07)
|
-1.04
(0.07)
|
| Week 8 |
-1.50
(0.07)
|
-1.17
(0.08)
|
-1.36
(0.08)
|
| Week 12 |
-1.65
(0.07)
|
-1.38
(0.07)
|
-1.43
(0.07)
|
| EoT |
-1.66
(0.07)
|
-1.35
(0.07)
|
-1.43
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.008 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to -0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.002 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.55 to -0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.006 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to -0.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.002 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to -0.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
| Title | Number of Pads Used During the 3-Day Diary |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants who reported use of at least one pad in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
4.80
(0.28)
|
5.69
(0.36)
|
5.41
(0.29)
|
| Week 8 |
3.64
(0.24)
|
4.71
(0.37)
|
4.50
(0.29)
|
| Week 12 |
3.23
(0.22)
|
4.13
(0.28)
|
4.07
(0.28)
|
| EoT |
3.29
(0.22)
|
4.27
(0.28)
|
4.17
(0.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.545 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.06 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.010 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 0.95 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.007 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.79 | |
| Confidence Interval |
(2-Sided) 95% 0.67 to 0.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 0.92 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Number of Nocturia Episodes |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one nocturia episode reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-0.28
(0.03)
|
-0.27
(0.03)
|
-0.29
(0.03)
|
| Week 8 |
-0.37
(0.03)
|
-0.35
(0.03)
|
-0.37
(0.03)
|
| Week 12 |
-0.46
(0.03)
|
-0.38
(0.03)
|
-0.41
(0.03)
|
| EoT |
-0.43
(0.03)
|
-0.37
(0.03)
|
-0.41
(0.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.836 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 0.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.617 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.12 to 0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.134 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.07 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EOT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.174 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.16 to 0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
| Title | Number of Nocturia Episodes Reported Over 3-Day Diary |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one nocturia episode reported in baseline diary were included. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
3.63
(0.12)
|
3.59
(0.12)
|
3.58
(0.12)
|
| Week 8 |
3.33
(0.12)
|
3.35
(0.12)
|
3.32
(0.12)
|
| Week 12 |
3.12
(0.13)
|
3.26
(0.12)
|
3.23
(0.12)
|
| EoT |
3.16
(0.12)
|
3.28
(0.11)
|
3.19
(0.12)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.993 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 1.00 | |
| Confidence Interval |
(2-Sided) 95% 0.93 to 1.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.736 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.99 | |
| Confidence Interval |
(2-Sided) 95% 0.90 to 1.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.121 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.93 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 1.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.172 |
| Comments | p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. | |
| Method | Mixed Effects Poisson | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 1.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| No problems -> no problems |
409
56.3%
|
370
50.8%
|
374
52%
|
| No problems -> slight problems |
33
4.5%
|
35
4.8%
|
36
5%
|
| No problems -> moderate problems |
14
1.9%
|
11
1.5%
|
11
1.5%
|
| No problems -> severe problems |
0
0%
|
7
1%
|
4
0.6%
|
| No problems -> extreme problems |
0
0%
|
1
0.1%
|
0
0%
|
| No problems -> no data |
2
0.3%
|
4
0.5%
|
5
0.7%
|
| Slight problems -> no problems |
52
7.2%
|
58
8%
|
60
8.3%
|
| Slight problems -> slight problems |
43
5.9%
|
46
6.3%
|
40
5.6%
|
| Slight problems -> moderate problems |
15
2.1%
|
28
3.8%
|
16
2.2%
|
| Slight problems -> severe problems |
1
0.1%
|
3
0.4%
|
3
0.4%
|
| Slight problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Slight problems -> no data |
2
0.3%
|
0
0%
|
0
0%
|
| Moderate problems -> no problems |
24
3.3%
|
36
4.9%
|
25
3.5%
|
| Moderate problems -> slight problems |
25
3.4%
|
18
2.5%
|
23
3.2%
|
| Moderate problems -> moderate problems |
28
3.9%
|
28
3.8%
|
40
5.6%
|
| Moderate problems -> severe problems |
2
0.3%
|
3
0.4%
|
7
1%
|
| Moderate problems -> extreme problems |
0
0%
|
1
0.1%
|
0
0%
|
| Moderate problems -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Severe problems -> no problems |
7
1%
|
8
1.1%
|
2
0.3%
|
| Severe problems -> slight problems |
6
0.8%
|
7
1%
|
7
1%
|
| Severe problems -> moderate problems |
17
2.3%
|
11
1.5%
|
11
1.5%
|
| Severe problems -> severe problems |
12
1.7%
|
10
1.4%
|
14
1.9%
|
| Severe problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Severe problems -> no data |
1
0.1%
|
1
0.1%
|
0
0%
|
| Extreme problems -> no problems |
3
0.4%
|
2
0.3%
|
2
0.3%
|
| Extreme problems -> slight problems |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme problems -> moderate problems |
1
0.1%
|
1
0.1%
|
1
0.1%
|
| Extreme problems -> severe problems |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| No data -> no problems |
4
0.6%
|
9
1.2%
|
13
1.8%
|
| No data -> slight problems |
2
0.3%
|
4
0.5%
|
1
0.1%
|
| No data -> moderate problems |
0
0%
|
3
0.4%
|
3
0.4%
|
| No data -> severe problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| No problems -> no problems |
548
75.4%
|
541
74.3%
|
548
76.2%
|
| No problems -> slight problems |
28
3.9%
|
26
3.6%
|
25
3.5%
|
| No problems -> moderate problems |
0
0%
|
14
1.9%
|
7
1%
|
| No problems -> severe problems |
3
0.4%
|
0
0%
|
2
0.3%
|
| No problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| No problems -> no data |
6
0.8%
|
5
0.7%
|
4
0.6%
|
| Slight problems -> no problems |
37
5.1%
|
25
3.4%
|
32
4.5%
|
| Slight problems -> slight problems |
23
3.2%
|
24
3.3%
|
22
3.1%
|
| Slight problems -> moderate problems |
9
1.2%
|
7
1%
|
9
1.3%
|
| Slight problems -> severe problems |
1
0.1%
|
0
0%
|
0
0%
|
| Slight problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Slight problems -> no data |
0
0%
|
0
0%
|
1
0.1%
|
| Moderate problems -> no problems |
12
1.7%
|
16
2.2%
|
7
1%
|
| Moderate problems -> slight problems |
9
1.2%
|
9
1.2%
|
5
0.7%
|
| Moderate problems -> moderate problems |
11
1.5%
|
7
1%
|
12
1.7%
|
| Moderate problems -> severe problems |
0
0%
|
2
0.3%
|
2
0.3%
|
| Moderate problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Moderate problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| Severe problems -> no problems |
7
1%
|
5
0.7%
|
0
0%
|
| Severe problems -> slight problems |
2
0.3%
|
2
0.3%
|
2
0.3%
|
| Severe problems -> moderate problems |
2
0.3%
|
1
0.1%
|
2
0.3%
|
| Severe problems -> severe problems |
1
0.1%
|
4
0.5%
|
1
0.1%
|
| Severe problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Severe problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> no problems |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> slight problems |
0
0%
|
1
0.1%
|
0
0%
|
| Extreme problems -> moderate problems |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> severe problems |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| No data -> no problems |
6
0.8%
|
14
1.9%
|
17
2.4%
|
| No data -> slight problems |
0
0%
|
2
0.3%
|
0
0%
|
| No data -> moderate problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> severe problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| No problems -> no problems |
397
54.6%
|
384
52.7%
|
379
52.7%
|
| No problems -> slight problems |
38
5.2%
|
30
4.1%
|
42
5.8%
|
| No problems -> moderate problems |
12
1.7%
|
19
2.6%
|
11
1.5%
|
| No problems -> severe problems |
1
0.1%
|
4
0.5%
|
1
0.1%
|
| No problems -> extreme problems |
0
0%
|
0
0%
|
1
0.1%
|
| No problems -> no data |
4
0.6%
|
3
0.4%
|
3
0.4%
|
| Slight problems -> no problems |
75
10.3%
|
81
11.1%
|
78
10.8%
|
| Slight problems -> slight problems |
46
6.3%
|
45
6.2%
|
37
5.1%
|
| Slight problems -> moderate problems |
12
1.7%
|
16
2.2%
|
15
2.1%
|
| Slight problems -> severe problems |
1
0.1%
|
1
0.1%
|
3
0.4%
|
| Slight problems -> extreme problems |
0
0%
|
1
0.1%
|
0
0%
|
| Slight problems -> no data |
0
0%
|
1
0.1%
|
2
0.3%
|
| Moderate problems -> no problems |
29
4%
|
35
4.8%
|
25
3.5%
|
| Moderate problems -> slight problems |
22
3%
|
20
2.7%
|
28
3.9%
|
| Moderate problems -> moderate problems |
22
3%
|
18
2.5%
|
21
2.9%
|
| Moderate problems -> severe problems |
3
0.4%
|
3
0.4%
|
4
0.6%
|
| Moderate problems -> extreme problems |
1
0.1%
|
0
0%
|
0
0%
|
| Moderate problems -> no data |
2
0.3%
|
1
0.1%
|
0
0%
|
| Severe problems -> no problems |
9
1.2%
|
8
1.1%
|
12
1.7%
|
| Severe problems -> slight problems |
7
1%
|
5
0.7%
|
1
0.1%
|
| Severe problems -> moderate problems |
7
1%
|
6
0.8%
|
9
1.3%
|
| Severe problems -> severe problems |
5
0.7%
|
7
1%
|
9
1.3%
|
| Severe problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Severe problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> no problems |
2
0.3%
|
0
0%
|
0
0%
|
| Extreme problems -> slight problems |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme problems -> moderate problems |
3
0.4%
|
1
0.1%
|
0
0%
|
| Extreme problems -> severe problems |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme problems -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| Extreme problems -> no data |
0
0%
|
0
0%
|
0
0%
|
| No data -> no problems |
5
0.7%
|
11
1.5%
|
15
2.1%
|
| No data -> slight problems |
1
0.1%
|
4
0.5%
|
1
0.1%
|
| No data -> moderate problems |
0
0%
|
1
0.1%
|
1
0.1%
|
| No data -> severe problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> extreme problems |
0
0%
|
0
0%
|
0
0%
|
| No data -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| No pain -> no pain |
299
41.1%
|
290
39.8%
|
283
39.4%
|
| No pain -> slight pain |
45
6.2%
|
62
8.5%
|
51
7.1%
|
| No pain -> moderate pain |
12
1.7%
|
14
1.9%
|
17
2.4%
|
| No pain -> severe pain |
3
0.4%
|
9
1.2%
|
2
0.3%
|
| No pain -> extreme pain |
0
0%
|
0
0%
|
1
0.1%
|
| No pain -> no data |
4
0.6%
|
4
0.5%
|
3
0.4%
|
| Slight pain -> no pain |
79
10.9%
|
82
11.3%
|
81
11.3%
|
| Slight pain -> slight pain |
58
8%
|
64
8.8%
|
55
7.6%
|
| Slight pain -> moderate pain |
28
3.9%
|
17
2.3%
|
31
4.3%
|
| Slight pain -> severe pain |
0
0%
|
2
0.3%
|
5
0.7%
|
| Slight pain -> extreme pain |
1
0.1%
|
2
0.3%
|
0
0%
|
| Slight pain -> no data |
0
0%
|
0
0%
|
2
0.3%
|
| Moderate pain -> no pain |
39
5.4%
|
36
4.9%
|
21
2.9%
|
| Moderate pain -> slight pain |
37
5.1%
|
36
4.9%
|
39
5.4%
|
| Moderate pain -> moderate pain |
34
4.7%
|
30
4.1%
|
39
5.4%
|
| Moderate pain -> severe pain |
7
1%
|
4
0.5%
|
8
1.1%
|
| Moderate pain -> extreme pain |
0
0%
|
1
0.1%
|
0
0%
|
| Moderate pain -> no data |
2
0.3%
|
1
0.1%
|
0
0%
|
| Severe pain -> no pain |
7
1%
|
4
0.5%
|
10
1.4%
|
| Severe pain -> slight pain |
12
1.7%
|
7
1%
|
4
0.6%
|
| Severe pain -> moderate pain |
11
1.5%
|
16
2.2%
|
16
2.2%
|
| Severe pain -> severe pain |
10
1.4%
|
4
0.5%
|
9
1.3%
|
| Severe pain -> extreme pain |
0
0%
|
1
0.1%
|
1
0.1%
|
| Severe pain -> no data |
0
0%
|
0
0%
|
0
0%
|
| Extreme pain -> no pain |
4
0.6%
|
1
0.1%
|
0
0%
|
| Extreme pain -> slight pain |
0
0%
|
1
0.1%
|
1
0.1%
|
| Extreme pain -> moderate pain |
1
0.1%
|
0
0%
|
1
0.1%
|
| Extreme pain -> severe pain |
6
0.8%
|
1
0.1%
|
1
0.1%
|
| Extreme pain -> extreme pain |
1
0.1%
|
0
0%
|
0
0%
|
| Extreme pain -> no data |
0
0%
|
0
0%
|
0
0%
|
| No data -> no pain |
4
0.6%
|
8
1.1%
|
11
1.5%
|
| No data -> slight pain |
1
0.1%
|
3
0.4%
|
4
0.6%
|
| No data -> moderate pain |
1
0.1%
|
5
0.7%
|
2
0.3%
|
| No data -> severe pain |
0
0%
|
0
0%
|
0
0%
|
| No data -> extreme pain |
0
0%
|
0
0%
|
0
0%
|
| No data -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Not anxious -> not anxious |
322
44.3%
|
300
41.2%
|
307
42.7%
|
| Not anxious -> slightly anxious |
43
5.9%
|
39
5.4%
|
43
6%
|
| Not anxious -> moderately anxious |
11
1.5%
|
17
2.3%
|
15
2.1%
|
| Not anxious -> severely anxious |
2
0.3%
|
2
0.3%
|
3
0.4%
|
| Not anxious-> extremely anxious |
0
0%
|
0
0%
|
0
0%
|
| Not anxious -> no data |
4
0.6%
|
3
0.4%
|
3
0.4%
|
| Slightly anxious -> not anxious |
107
14.7%
|
99
13.6%
|
90
12.5%
|
| Slightly anxious -> slightly anxious |
56
7.7%
|
60
8.2%
|
69
9.6%
|
| Slightly anxious -> moderately anxious |
13
1.8%
|
11
1.5%
|
23
3.2%
|
| Slightly anxious -> severely anxious |
1
0.1%
|
2
0.3%
|
2
0.3%
|
| Slightly anxious -> extremely anxious |
0
0%
|
0
0%
|
0
0%
|
| Slightly anxious -> no data |
1
0.1%
|
2
0.3%
|
2
0.3%
|
| Moderately anxious -> not anxious |
36
5%
|
38
5.2%
|
34
4.7%
|
| Moderately anxious -> slightly anxious |
36
5%
|
40
5.5%
|
33
4.6%
|
| Moderately anxious -> moderately anxious |
22
3%
|
26
3.6%
|
17
2.4%
|
| Moderately anxious -> severely anxious |
3
0.4%
|
7
1%
|
1
0.1%
|
| Moderately anxious -> extremely anxious |
0
0%
|
3
0.4%
|
1
0.1%
|
| Moderately anxious -> no data |
0
0%
|
0
0%
|
0
0%
|
| Severely anxious -> not anxious |
10
1.4%
|
8
1.1%
|
8
1.1%
|
| Severely anxious -> slightly anxious |
9
1.2%
|
5
0.7%
|
5
0.7%
|
| Severely anxious -> moderately anxious |
6
0.8%
|
6
0.8%
|
11
1.5%
|
| Severely anxious -> severely anxious |
5
0.7%
|
8
1.1%
|
7
1%
|
| Severely anxious -> extremely anxious |
0
0%
|
3
0.4%
|
0
0%
|
| Severely anxious -> no data |
0
0%
|
0
0%
|
0
0%
|
| Extremely anxious -> not anxious |
1
0.1%
|
4
0.5%
|
1
0.1%
|
| Extremely anxious -> slightly anxious |
2
0.3%
|
1
0.1%
|
1
0.1%
|
| Extremely anxious -> moderately anxious |
4
0.6%
|
2
0.3%
|
3
0.4%
|
| Extremely anxious -> severely anxious |
4
0.6%
|
1
0.1%
|
1
0.1%
|
| Extremely anxious -> extremely anxious |
1
0.1%
|
2
0.3%
|
1
0.1%
|
| Extremely anxious -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| No data -> not anxious |
5
0.7%
|
13
1.8%
|
11
1.5%
|
| No data -> slightly anxious |
0
0%
|
2
0.3%
|
5
0.7%
|
| No data -> moderately anxious |
1
0.1%
|
1
0.1%
|
1
0.1%
|
| No data -> severely anxious |
0
0%
|
0
0%
|
0
0%
|
| No data -> extremely anxious |
0
0%
|
0
0%
|
0
0%
|
| No data -> no data |
1
0.1%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-16.68
(0.65)
|
-13.79
(0.65)
|
-15.82
(0.65)
|
| Week 8 |
-22.86
(0.68)
|
-18.36
(0.69)
|
-19.34
(0.69)
|
| Week 12 |
-27.90
(0.71)
|
-22.31
(0.71)
|
-24.09
(0.71)
|
| EoT |
-26.89
(0.69)
|
-21.93
(0.70)
|
-23.59
(0.70)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.002 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -2.89 | |
| Confidence Interval |
(2-Sided) 95% -4.68 to -1.10 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.91 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -4.50 | |
| Confidence Interval |
(2-Sided) 95% -6.40 to -2.60 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -5.59 | |
| Confidence Interval |
(2-Sided) 95% -7.56 to -3.62 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.00 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -4.96 | |
| Confidence Interval |
(2-Sided) 95% -6.88 to -3.04 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.98 |
|
| Estimation Comments | ||
| Title | Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
12.95
(0.59)
|
11.03
(0.59)
|
12.44
(0.59)
|
| Week 8 |
17.58
(0.63)
|
15.26
(0.63)
|
14.60
(0.64)
|
| Week 12 |
21.40
(0.66)
|
17.91
(0.67)
|
17.72
(0.66)
|
| EoT |
20.78
(0.65)
|
17.63
(0.65)
|
17.40
(0.65)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.021 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.92 | |
| Confidence Interval |
(2-Sided) 95% 0.29 to 3.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.010 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.31 | |
| Confidence Interval |
(2-Sided) 95% 0.56 to 4.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.89 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.49 | |
| Confidence Interval |
(2-Sided) 95% 1.65 to 5.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.94 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.15 | |
| Confidence Interval |
(2-Sided) 95% 1.35 to 4.95 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.92 |
|
| Estimation Comments | ||
| Title | Change From Baseline in OAB-q HRQL Subscale Score: Coping |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
15.17
(0.68)
|
12.27
(0.68)
|
14.25
(0.68)
|
| Week 8 |
20.82
(0.74)
|
17.47
(0.74)
|
16.87
(0.74)
|
| Week 12 |
25.16
(0.78)
|
20.45
(0.78)
|
20.20
(0.78)
|
| EoT |
24.48
(0.75)
|
20.19
(0.76)
|
19.90
(0.76)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.90 | |
| Confidence Interval |
(2-Sided) 95% 1.02 to 4.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.35 | |
| Confidence Interval |
(2-Sided) 95% 1.29 to 5.40 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.05 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 4.71 | |
| Confidence Interval |
(2-Sided) 95% 2.55 to 6.87 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.10 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 4.29 | |
| Confidence Interval |
(2-Sided) 95% 2.20 to 6.39 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.07 |
|
| Estimation Comments | ||
| Title | Change From Baseline in OAB-q HRQL Subscale Score: Concern |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
13.79
(0.68)
|
11.85
(0.68)
|
13.82
(0.69)
|
| Week 8 |
18.87
(0.70)
|
16.36
(0.71)
|
15.88
(0.71)
|
| Week 12 |
22.85
(0.74)
|
19.24
(0.75)
|
19.67
(0.74)
|
| Week EoT |
22.28
(0.72)
|
19.00
(0.73)
|
19.28
(0.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.044 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.94 | |
| Confidence Interval |
(2-Sided) 95% 0.05 to 3.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.012 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.50 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 4.46 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.00 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.61 | |
| Confidence Interval |
(2-Sided) 95% 1.54 to 5.67 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.05 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 3.28 | |
| Confidence Interval |
(2-Sided) 95% 1.27 to 5.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | ||
| Title | Change From Baseline in OAB-q HRQL Subscale Score: Sleep |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
11.58
(0.68)
|
11.04
(0.68)
|
11.16
(0.69)
|
| Week 8 |
16.18
(0.71)
|
14.57
(0.71)
|
13.72
(0.71)
|
| Week 12 |
20.00
(0.74)
|
17.74
(0.74)
|
16.84
(0.74)
|
| Week EoT |
19.16
(0.72)
|
17.30
(0.73)
|
16.55
(0.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.575 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% -1.35 to 2.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.109 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.61 | |
| Confidence Interval |
(2-Sided) 95% -0.36 to 3.58 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.00 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.032 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.26 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 4.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.05 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.069 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.86 | |
| Confidence Interval |
(2-Sided) 95% -0.15 to 3.87 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.02 |
|
| Estimation Comments | ||
| Title | Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
9.58
(0.59)
|
7.85
(0.59)
|
8.95
(0.59)
|
| Week 8 |
11.93
(0.60)
|
10.84
(0.60)
|
10.16
(0.60)
|
| Week 12 |
14.70
(0.61)
|
12.08
(0.61)
|
11.98
(0.61)
|
| EoT |
14.39
(0.60)
|
11.91
(0.60)
|
11.72
(0.61)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.037 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.73 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 3.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.199 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 95% -0.57 to 2.76 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.62 | |
| Confidence Interval |
(2-Sided) 95% 0.92 to 4.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.87 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 2.48 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 4.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
1.2
(0.1)
|
0.8
(0.1)
|
1.1
(0.1)
|
| Week 8 |
1.5
(0.1)
|
1.2
(0.1)
|
1.3
(0.1)
|
| Week 12 |
1.9
(0.1)
|
1.4
(0.1)
|
1.6
(0.1)
|
| EoT |
1.8
(0.1)
|
1.4
(0.1)
|
1.6
(0.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.019 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 0.5 | |
| Confidence Interval |
(2-Sided) 95% 0.3 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Patient Perception Bladder Control (PPBC) Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
-0.9
(0.0)
|
-0.6
(0.0)
|
-0.7
(0.0)
|
| Week 8 |
-1.2
(0.0)
|
-1.0
(0.0)
|
-1.0
(0.0)
|
| Week 12 |
-1.5
(0.0)
|
-1.2
(0.0)
|
-1.3
(0.0)
|
| EoT |
-1.5
(0.0)
|
-1.2
(0.0)
|
-1.3
(0.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to -0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
| Title | Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| PIBS Very Much Improved |
227
31.2%
|
152
20.9%
|
171
23.8%
|
| PIBS Much Improved |
257
35.4%
|
264
36.3%
|
284
39.5%
|
| PIBS Minimally Improved |
135
18.6%
|
170
23.4%
|
152
21.1%
|
| PIBS No Change |
25
3.4%
|
55
7.6%
|
56
7.8%
|
| PIBS Minimally Worse |
7
1%
|
11
1.5%
|
4
0.6%
|
| PIBS Much Worse |
4
0.6%
|
4
0.5%
|
6
0.8%
|
| PIBS Very Much Worse |
0
0%
|
1
0.1%
|
1
0.1%
|
| PIGH Very Much Improved |
144
19.8%
|
104
14.3%
|
108
15%
|
| PIGH Much Improved |
239
32.9%
|
236
32.4%
|
244
33.9%
|
| PIGH Minimally Improved |
143
19.7%
|
147
20.2%
|
146
20.3%
|
| PIGH No Change |
113
15.5%
|
142
19.5%
|
160
22.3%
|
| PIGH Minimally Worse |
14
1.9%
|
23
3.2%
|
10
1.4%
|
| PIGH Much Worse |
1
0.1%
|
4
0.5%
|
4
0.6%
|
| PIGH Very Much Worse |
1
0.1%
|
1
0.1%
|
2
0.3%
|
| CIBS Very Much Improved |
184
25.3%
|
118
16.2%
|
141
19.6%
|
| CIBS Much Improved |
311
42.8%
|
316
43.4%
|
329
45.8%
|
| CIBS Minimally Improved |
141
19.4%
|
164
22.5%
|
155
21.6%
|
| CIBS No Change |
23
3.2%
|
56
7.7%
|
40
5.6%
|
| CIBS Minimally Worse |
4
0.6%
|
8
1.1%
|
5
0.7%
|
| CIBS Much Worse |
4
0.6%
|
3
0.4%
|
5
0.7%
|
| CIBS Very Much Worse |
3
0.4%
|
3
0.4%
|
4
0.6%
|
| Title | Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 Hours |
|---|---|
| Description | Incontinence was defined as any involuntary leakage of urine. |
| Time Frame | Weeks 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
52.5
7.2%
|
43.3
5.9%
|
49.0
6.8%
|
| Week 8 |
66.9
9.2%
|
57.6
7.9%
|
61.8
8.6%
|
| Week 12 |
72.4
10%
|
64.0
8.8%
|
66.9
9.3%
|
| EoT |
71.2
9.8%
|
63.1
8.7%
|
66.6
9.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.48 | |
| Confidence Interval |
(2-Sided) 95% 1.19 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.57 | |
| Confidence Interval |
(2-Sided) 95% 1.25 to 1.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.54 | |
| Confidence Interval |
(2-Sided) 95% 1.21 to 1.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.51 | |
| Confidence Interval |
(2-Sided) 95% 1.20 to 1.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Zero Incontinence Episodes Postbaseline |
|---|---|
| Description | Incontinence was defined as any involuntary leakage of urine. |
| Time Frame | Weeks 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
23.5
3.2%
|
20.0
2.7%
|
22.1
3.1%
|
| Week 8 |
40.4
5.6%
|
31.6
4.3%
|
34.3
4.8%
|
| Week 12 |
47.3
6.5%
|
39.5
5.4%
|
40.7
5.7%
|
| EoT |
46.0
6.3%
|
37.9
5.2%
|
40.2
5.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.119 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.24 | |
| Confidence Interval |
(2-Sided) 95% 0.95 to 1.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.56 | |
| Confidence Interval |
(2-Sided) 95% 1.23 to 1.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.002 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.44 | |
| Confidence Interval |
(2-Sided) 95% 1.14 to 1.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.47 | |
| Confidence Interval |
(2-Sided) 95% 1.17 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | Micturitions were defined as voluntary urinations (excluding incontinence only episodes). |
| Time Frame | Weeks 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
21.0
2.9%
|
18.7
2.6%
|
20.2
2.8%
|
| Week 8 |
28.1
3.9%
|
22.4
3.1%
|
26.3
3.7%
|
| Week 12 |
31.4
4.3%
|
24.8
3.4%
|
28.0
3.9%
|
| EoT |
30.2
4.2%
|
25.0
3.4%
|
27.7
3.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.305 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.15 | |
| Confidence Interval |
(2-Sided) 95% 0.88 to 1.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.014 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.37 | |
| Confidence Interval |
(2-Sided) 95% 1.06 to 1.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.012 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.37 | |
| Confidence Interval |
(2-Sided) 95% 1.07 to 1.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.036 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% 1.02 to 1.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With at Least a 10-Point Improvement From Baseline in OAB-q Symptom Bother Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
67.9
9.3%
|
58.2
8%
|
61.9
8.6%
|
| Week 8 |
77.2
10.6%
|
66.4
9.1%
|
69.1
9.6%
|
| Week 12 |
83.5
11.5%
|
72.1
9.9%
|
75.4
10.5%
|
| EoT |
81.7
11.2%
|
71.7
9.8%
|
74.6
10.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.49 | |
| Confidence Interval |
(2-Sided) 95% 1.18 to 1.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.69 | |
| Confidence Interval |
(2-Sided) 95% 1.31 to 2.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.96 | |
| Confidence Interval |
(2-Sided) 95% 1.47 to 2.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.75 | |
| Confidence Interval |
(2-Sided) 95% 1.34 to 2.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With at Least a 10-Point Improvement From Baseline in HRQL Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
52.6
7.2%
|
44.5
6.1%
|
48.1
6.7%
|
| Week 8 |
63.6
8.7%
|
54.8
7.5%
|
53.8
7.5%
|
| Week 12 |
70.5
9.7%
|
60.8
8.4%
|
60.4
8.4%
|
| EoT |
68.6
9.4%
|
60.6
8.3%
|
60.1
8.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p<0.05 indicates superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.44 | |
| Confidence Interval |
(2-Sided) 95% 1.14 to 1.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | p<0.05 indicates superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.51 | |
| Confidence Interval |
(2-Sided) 95% 1.18 to 1.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p<0.05 indicates superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.64 | |
| Confidence Interval |
(2-Sided) 95% 1.27 to 2.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | p<0.05 indicates superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.50 | |
| Confidence Interval |
(2-Sided) 95% 1.17 to 1.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With at Least a 1-Point Improvement From Baseline in PPBC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
61.1
8.4%
|
52.1
7.2%
|
56.3
7.8%
|
| Week 8 |
70.1
9.6%
|
62.1
8.5%
|
64.6
9%
|
| Week 12 |
77.9
10.7%
|
70.4
9.7%
|
72.7
10.1%
|
| EoT |
76.5
10.5%
|
69.5
9.5%
|
71.9
10%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.42 | |
| Confidence Interval |
(2-Sided) 95% 1.13 to 1.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.44 | |
| Confidence Interval |
(2-Sided) 95% 1.12 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.50 | |
| Confidence Interval |
(2-Sided) 95% 1.15 to 1.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.006 |
| Comments | p<0.05 indicated superiority in favor of treatment group with highest response. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.43 | |
| Confidence Interval |
(2-Sided) 95% 1.11 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Major (at Least 2-Point) Improvement From Baseline in PPBC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 707 | 705 | 698 |
| Week 4 |
26.6
3.7%
|
21.6
3%
|
21.6
3%
|
| Week 8 |
39.5
5.4%
|
31.5
4.3%
|
31.8
4.4%
|
| Week 12 |
51.8
7.1%
|
39.8
5.5%
|
43.8
6.1%
|
| EoT |
49.8
6.9%
|
39.1
5.4%
|
43.2
6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 4 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.065 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.28 | |
| Confidence Interval |
(2-Sided) 95% 0.99 to 1.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 8 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.41 | |
| Confidence Interval |
(2-Sided) 95% 1.11 to 1.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | Week 12 odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.64 | |
| Confidence Interval |
(2-Sided) 95% 1.30 to 2.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Combination (Solifenacin + Mirabegron), Solifenacin 5 mg |
|---|---|---|
| Comments | EoT odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.55 | |
| Confidence Interval |
(2-Sided) 95% 1.24 to 1.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of the Safety Analysis Set, the SAF comprised all randomized participants who received at least 1 dose of double-blind treatment. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 725 | 728 | 719 |
| AEs |
260
35.8%
|
241
33.1%
|
283
39.4%
|
| Drug-related AEs |
141
19.4%
|
125
17.2%
|
161
22.4%
|
| Serious Adverse Events (SAEs) |
13
1.8%
|
10
1.4%
|
15
2.1%
|
| Drug-related SAEs |
1
0.1%
|
0
0%
|
3
0.4%
|
| AEs Leading to Perm. Disc. of Study Drug |
11
1.5%
|
11
1.5%
|
11
1.5%
|
| Drug-related AEs Leading to Perm. Disc. of Drug |
9
1.2%
|
10
1.4%
|
9
1.3%
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Post Void Residual (PVR) Volume |
|---|---|
| Description | PVR Volume was assessed by bladder scan. |
| Time Frame | Baseline and weeks 4, 8 & 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of the SAF with data available at each time point. |
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg |
|---|---|---|---|
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. |
| Measure Participants | 725 | 728 | 719 |
| Week 4 |
1.545
(40.313)
|
2.821
(38.588)
|
7.308
(72.122)
|
| Week 8 |
2.245
(38.347)
|
1.117
(36.470)
|
7.232
(60.096)
|
| Week 12 |
6.356
(51.067)
|
2.337
(42.147)
|
6.552
(48.505)
|
| EoT |
5.478
(51.595)
|
3.046
(43.499)
|
7.354
(54.121)
|
Adverse Events
| Time Frame | From first dose of double blind treatment until 30 days after last dose (up to 16 weeks) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Population consisted of the SAF. An AE was 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. | |||||
| Arm/Group Title | Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg | |||
| Arm/Group Description | Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. | Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period | Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. | |||
All Cause Mortality |
||||||
| Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/725 (1.8%) | 10/728 (1.4%) | 15/719 (2.1%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Atrial fibrillation | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Atrioventricular block complete | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Endocrine disorders | ||||||
| Goitre | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal hernia | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Abdominal pain | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Inguinal hernia | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Pancreatitis | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| General disorders | ||||||
| Adhesion | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Non-cardiac chest pain | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Pyrexia | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Hepatic pain | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Liver disorder | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Immune system disorders | ||||||
| Hypersensitivity | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Infections and infestations | ||||||
| Appendicitis | 1/725 (0.1%) | 1 | 1/728 (0.1%) | 1 | 1/719 (0.1%) | 1 |
| Encephalitis herpes | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Pneumonia | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Multiple fractures | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Arteriogram coronary normal | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Arthroscopy | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Aspartate aminotransferase increased | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Colonoscopy | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Gamma-glutamyltransferase increased | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Fracture pain | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 2 |
| Mobility decreased | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adrenal adenoma | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Anal cancer | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Intraductal proliferative breast lesion | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Nervous system disorders | ||||||
| Polyneuropathy | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Transient ischaemic attack | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Reproductive system and breast disorders | ||||||
| Cervix haemorrhage uterine | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory tract oedema | 1/725 (0.1%) | 1 | 0/728 (0%) | 0 | 0/719 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Urticaria | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Surgical and medical procedures | ||||||
| Joint resurfacing surgery | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Skin neoplasm excision | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertensive crisis | 0/725 (0%) | 0 | 0/728 (0%) | 0 | 1/719 (0.1%) | 1 |
| Thrombosis | 0/725 (0%) | 0 | 1/728 (0.1%) | 1 | 0/719 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Combination (Solifenacin + Mirabegron) | Solifenacin 5 mg | Solifenacin 10 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 43/725 (5.9%) | 41/728 (5.6%) | 68/719 (9.5%) | |||
| Gastrointestinal disorders | ||||||
| Dry mouth | 43/725 (5.9%) | 44 | 41/728 (5.6%) | 44 | 68/719 (9.5%) | 70 |
Limitations/Caveats
One participant was randomized to the Combination arm, but actually received Solifenacin 10 mg. In terms of actual treatment received, the participant was allocated to the solifenacin 10 mg arm.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The PI shall provide sponsor with a copy of proposed publication/presentation for review and comment at least 30 days prior to submission for publication/presentation. The sponsor can delay communications regarding trial results for an additional 90 days from the time submitted to the sponsor for review. The sponsor can require changes to the communication and can extend the delay.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure |
|---|---|
| Organization | Astellas Pharma Europe Ltd |
| Phone | +44 (0)20 3379 8000 |
| Astellas.resultsdisclosure@astellas.com |
Responsible Party:
Astellas Pharma Europe Ltd.
ClinicalTrials.gov Identifier:
NCT01908829
Other Study ID Numbers:
- 905-EC-012
- 2012-005401-41
First Posted:
Jul 26, 2013
Last Update Posted:
Aug 15, 2018
Last Verified:
Jul 1, 2018