Phase 3
Completed N=3,527
This Was a Multinational Study Comparing the Efficacy and Safety of Two Medicines , Solifenacin Succinate and Mirabegron Taken Together, or Separately, or a Mock Treatment (Placebo) in Subjects With Symptoms of Overactive Bladder
Urinary Bladder Overactive · Urinary Bladder Diseases\Urologic Diseases · Overactive Bladder · Urgency Incontinence
Source: ClinicalTrials.gov NCT01972841 ↗
Enrolled (actual)
3,527
Serious AEs
1.6%
Results posted
Jun 2018
Primary outcomePrimary: Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours — -1.34; -1.70; -1.76; -1.79 incontinence episodes — p=0.072
Summary
The purpose of this study was to examine how well two medicines (solifenacin succinate and mirabegron) combined work compared to each medicine alone in the treatment of bladder problems.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours |
-1.34; -1.70; -1.76; -1.79; -2.04; -1.98 | 0.072 |
| PRIMARY Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours |
-1.64; -2.00; -2.03; -2.20; -2.49; -2.59 | 0.040 sig |
| SECONDARY Change From Baseline to EoT in Mean Volume Voided Per Micturition |
8.44; 13.32; 21.99; 30.99; 34.84; 39.73 | 0.219 |
| SECONDARY Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score |
-19.45; -23.93; -26.14; -26.44; -31.06; -32.24 | <0.001 sig |
| SECONDARY Change From Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS) |
1.42; 2.16; 2.18; 2.28; 2.53; 2.55 | 0.077 |
| SECONDARY Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT |
18.09; 15.65; 12.90; 15.31; 12.51; 11.44 | 0.135 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes |
-5.23; -7.59; -8.99; -8.92; -9.62; -10.51 | 0.074 |
| SECONDARY Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes Per 24 Hours |
-0.74; -1.07; -1.24; -1.24; -1.38; -1.50 | — |
| SECONDARY Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions Per 24 Hours |
-1.02; -1.46; -1.44; -1.39; -1.67; -1.91 | — |
| SECONDARY Change From Baseline to Weeks 4, 8 and 12 in Mean Volume Voided Per Micturition |
6.95; 10.08; 15.52; 24.23; 25.54; 28.99 | — |
| SECONDARY Change From Baseline to EoT in Corrected Micturition Frequency |
0.15; -0.17; -0.97; -1.28; -1.10; -1.52 | 0.520 |
| SECONDARY Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EoT |
15.76; 13.36; 11.46; 13.19; 10.22; 9.33 | 0.110 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes |
-5.49; -7.07; -8.39; -8.53; -9.44; -10.23 | 0.114 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours |
-0.78; -1.00; -1.15; -1.19; -1.35; -1.47 | 0.134 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours |
-1.34; -1.95; -1.91; -2.14; -2.42; -2.66 | 0.074 |
| SECONDARY Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT |
9.62; 8.46; 9.11; 9.22; 8.40; 8.09 | 0.006 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes |
-1.27; -2.25; -1.80; -1.79; -2.39; -2.50 | 0.073 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours |
-0.17; -0.31; -0.25; -0.24; -0.33; -0.35 | 0.065 |
| SECONDARY Number of Pads Used at Weeks 4, 8, 12 and EoT |
15.62; 13.46; 10.05; 11.41; 9.71; 9.34 | 0.938 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used |
-3.69; -5.68; -7.83; -8.23; -7.61; -8.58 | 0.958 |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used Per 24 Hours |
-0.52; -0.81; -1.12; -1.19; -1.09; -1.23 | 0.993 |
| SECONDARY Number of Incontinence-Free Days at Weeks 4, 8, 12 and EoT |
2.25; 2.48; 2.98; 2.74; 3.08; 3.37 | 0.003 sig |
| SECONDARY Number of Days With < 8 Micturitions at Weeks 4, 8, 12 and EoT |
1.49; 1.74; 1.55; 1.86; 2.07; 2.11 | 0.039 sig |
| SECONDARY Number of Incontinence-Free Days With < 8 Micturitions at Weeks 4, 8, 12 and EoT |
0.64; 0.84; 0.87; 0.91; 1.21; 1.32 | 0.011 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC) |
-0.54; -0.72; -0.83; -0.81; -0.99; -1.07 | <0.001 sig |
| SECONDARY Change From Baseline to Weeks 4, 8 and 12 in the OAB-q Symptom Bother Score |
-13.84; -17.05; -18.98; -19.53; -23.46; -25.19 | — |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q Health-Related Quality of Life Questionnaire (HRQL) Total Score |
10.16; 13.54; 15.28; 14.78; 17.46; 17.95 | <0.001 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Coping |
11.74; 14.87; 17.68; 16.52; 19.31; 20.36 | 0.001 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Concern |
11.24; 15.89; 17.39; 17.18; 20.48; 21.09 | 0.001 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Sleep |
9.28; 12.70; 13.80; 13.08; 15.97; 16.66 | <0.001 sig |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Social |
7.07; 9.04; 10.19; 9.89; 11.55; 11.25 | 0.022 sig |
| SECONDARY Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT |
8.4; 13.9; 15.1; 13.5; 19.8; 27.1 | — |
| SECONDARY PGIC Scale: Impression in General Health at Week 12 and EoT |
4.8; 8.0; 7.3; 7.7; 10.3; 14.6 | — |
| SECONDARY Change From Baseline to EoT in European Quality of Life in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility |
204; 239; 225; 227; 449; 452 | — |
| SECONDARY Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-Care |
311; 324; 336; 319; 652; 647 | — |
| SECONDARY Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities |
196; 228; 219; 223; 434; 451 | — |
| SECONDARY Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort |
131; 175; 153; 154; 290; 317 | — |
| SECONDARY Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression |
157; 176; 187; 166; 360; 370 | — |
| SECONDARY Change From Baseline to Week 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed |
-2.98; -0.33; -1.72; -2.47; -2.06; -2.59 | — |
| SECONDARY Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Impairment While Working |
-11.27; -14.96; -12.25; -10.85; -14.69; -13.07 | — |
| SECONDARY Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Overall Work Impairment |
-12.23; -15.70; -12.92; -12.31; -16.31; -13.97 | — |
| SECONDARY Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Activity Impairment |
-11.49; -16.89; -14.99; -16.19; -19.60; -18.92 | — |
| SECONDARY Change From Baseline to Weeks 4, 8 and 12 in TS-VAS |
1.14; 1.68; 1.77; 1.82; 2.06; 2.13 | — |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Weeks 4, 8, 12 and EoT |
23.2; 24.9; 27.6; 28.9; 35.1; 37.3 | 0.035 sig |
| SECONDARY Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Weeks 4, 8, 12 and EoT |
56.4; 62.6; 69.9; 73.9; 73.9; 75.8 | 0.224 |
| SECONDARY Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQL Total Score at Weeks 4, 8, 12 and EoT |
45.3; 52.8; 59.7; 61.7; 62.9; 61.3 | 0.077 |
| SECONDARY Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Weeks 4, 8, 12 and EoT |
41.1; 45.3; 56.7; 53.2; 57.2; 60.6 | 0.251 |
| SECONDARY Percentage of Participants for Micturition Frequency Normalization at Weeks 4, 8, 12 and EoT |
24.1; 30.8; 25.4; 31.1; 36.0; 37.7 | 0.044 sig |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Weeks 4, 8, 12 and EoT |
12.8; 13.1; 16.7; 17.7; 23.9; 26.0 | 0.004 sig |
| SECONDARY Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Weeks 4, 8, 12 and EoT |
48.9; 52.8; 60.3; 58.1; 63.1; 62.7 | 0.065 |
| SECONDARY Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Weeks 4, 8, 12 and EoT |
15.9; 20.6; 22.4; 27.4; 31.1; 31.1 | 0.007 sig |
| SECONDARY Percentage of Participants Who Were Double Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Weeks 4, 8, 12 and EoT |
28.6; 34.8; 45.7; 44.9; 47.8; 52.3 | 0.381 |
| SECONDARY Percentage of Participants Who Were Double Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Weeks 4, 8, 12 and EoT |
23.2; 28.3; 39.8; 37.7; 40.4; 40.5 | 0.095 |
| SECONDARY Percentage of Participants Who Were Double Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT |
23.2; 27.9; 37.7; 34.5; 39.9; 42.9 | 0.210 |
| SECONDARY Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, at Least 10 Points Improvement on OAB-q Symptom Bother Scale and at Least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT |
17.8; 24.0; 33.6; 31.4; 37.5; 40.2 | 0.335 |
| SECONDARY Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, at Least 10 Points Improvement on OAB-q HRQL Total Score and at Least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT |
15.2; 20.6; 30.0; 28.6; 32.7; 33.4 | 0.416 |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
145; 135; 147; 149; 345; 314 | — |
| SECONDARY Change From Baseline to Weeks 4, 8, 12 and EoT in Postvoid Residual (PVR) Volume |
-0.8; 1.6; -2.1; 5.8; 7.2; 10.6 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean 24-hours, Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP) |
-1.00; -2.04; 0.96; 1.03; -0.85; 0.31 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) |
-0.70; -0.86; 0.22; 0.25; 0.03; 0.38 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Pulse Rate (PR) |
-0.83; 1.14; 2.32; 0.36; 0.40; 0.69 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean SBP in the Time to Maximum Concentration (Tmax) Window |
-2.71; 0.34; -1.03; -1.77; -1.55; -1.47 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean DBP in the Tmax Window |
-1.24; 0.09; -0.65; -0.48; -0.22; -0.71 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in Mean PR in the Tmax Window |
0.02; 2.39; 3.68; 0.47; -0.91; 0.67 | — |
| SECONDARY Maximum 1-hour Change From Time-matched Baseline in SBP at Weeks 4, 12 and EoT |
34.05; 31.14; 38.20; 35.16; 32.88; 32.80 | — |
| SECONDARY Maximum 1-hour Change From Time-matched Baseline in DBP at Weeks 4, 12 and EoT |
18.78; 19.15; 20.41; 20.02; 20.74; 20.27 | — |
| SECONDARY Maximum 1-hour Change From Time-matched Baseline in PR at Weeks 4, 12 and EoT |
22.34; 23.86; 25.12; 24.28; 21.48; 21.80 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in SBP Peak/Trough Difference |
-0.71; 0.14; -0.69; 0.85; -1.61; 0.41 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in DBP Peak/Trough Difference |
-0.76; -1.08; -0.20; -1.60; 0.39; -0.56 | — |
| SECONDARY Change From Baseline to Weeks 4, 12 and EoT in PR Peak/Trough Difference |
1.16; 0.46; 1.54; 0.78; -0.68; -0.51 | — |
Eligibility Criteria
Inclusion Criteria
- Subject was willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
- Subject had symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months;
Exclusion Criteria
- Subject had significant PVR volume (> 150 mL);
- Subject had a neurological cause for detrusor overactivity (e.g. neurogenic bladder, diabetic neuropathy with autonomic component or bladder involvement, or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component could be inferred when autonomic functions were affected, including heart rate, blood pressure, perspiration and digestion.
- Subject had an indwelling catheter or practices intermittent self catheterization.
- Subject had chronic inflammation such as bladder pain syndrome /interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.
- Subject had received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
- Subject had moderate to severe hepatic impairment
- Subject had severe renal impairment
- Subject had a clinically significant abnormal ECG
- Subject had a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
- Subject had an average QTcF interval > 450 ms for males or > 470 ms for females based on the triplicate ECGs completed at Screening or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
- Subject had severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
Data sourced from ClinicalTrials.gov (NCT01972841). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.