Phase 3
Completed N=1,829
A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder
Urinary Bladder Overactive · Overactive Bladder · Urgency Incontinence · Urinary Bladder Diseases\Urologic Diseases
Source: ClinicalTrials.gov NCT02045862 ↗
Enrolled (actual)
1,829
Serious AEs
3.7%
Results posted
Jun 2018
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) — 126; 134; 596; 61 Participants
Summary
The purpose of this study was to examine how well the combination of two medicines (solifenacin succinate and mirabegron) worked compared to each medicine alone in the treatment of bladder problems, and how safe they were for long term use.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
126; 134; 596; 61; 69; 306 | — |
| PRIMARY Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours |
-1.58; -1.90; -2.03 | <0.001 sig |
| PRIMARY Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours |
-2.10; -2.16; -2.58 | <0.001 sig |
| SECONDARY Change From Baseline to EoT in Mean Volume Voided Per Micturition |
21.83; 24.90; 37.67 | <0.001 sig |
| SECONDARY Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score |
-21.96; -24.91; -29.51 | <0.001 sig |
| SECONDARY Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS) |
2.19; 2.15; 2.73 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours |
-0.97; -1.29; -1.45; -1.31; -1.71; -1.78 | — |
| SECONDARY Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit |
14.88; 12.41; 10.80; 12.23; 9.23; 8.33 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit |
-6.77; -9.17; -10.31; -9.21; -12.05; -12.55 | <0.001 sig |
| SECONDARY Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit |
2.73; 3.35; 3.46; 3.30; 3.98; 4.17 | <0.001 sig |
| SECONDARY Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit |
1.03; 1.01; 1.33; 1.24; 1.48; 1.91 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours |
-0.93; -1.25; -1.43; -1.30; -1.64; -1.71 | <0.001 sig |
| SECONDARY Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit |
13.14; 11.21; 8.99; 10.37; 8.12; 6.95 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit |
-6.45; -8.77; -10.1; -9.06; -11.48; -11.99 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours |
-1.09; -1.36; -1.64; -1.63; -1.87; 2.16 | — |
| SECONDARY Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT) |
1.90; 1.60; 2.08; 2.07; 2.14; 2.66 | 0.002 sig |
| SECONDARY Change From Baseline to EoT in Corrected Micturition Frequency |
-0.72; -1.11; -1.51 | <0.001 sig |
| SECONDARY Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition |
15.34; 23.71; 34.89; 20.87; 27.08; 38.56 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours |
-1.93; -2.31; -2.68; -2.68; -3.02; -3.36 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours |
-0.20; -0.22; -0.34; -0.34; -0.38; -0.46 | 0.059 |
| SECONDARY Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit |
8.76; 9.23; 8.00; 7.93; 7.92; 7.17 | 0.067 |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit |
-1.56; -1.58; -2.39; -2.45; -2.78; -3.26 | 0.055 |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours |
-0.67; -0.96; -1.25; -1.12; -1.30; -1.49 | 0.002 sig |
| SECONDARY Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit |
12.67; 12.55; 8.75; 9.61; 9.47; 7.23 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit |
-4.74; -6.72; -8.89; -7.83; -9.21; 10.47 | 0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score |
-16.37; -20.82; -22.86; -19.69; -23.13; -26.88 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score |
11.67; 14.01; 15.69; 15.25; 16.41; 19.26 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping |
13.05; 15.40; 17.58; 17.57; 18.38; 21.64 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern |
13.24; 15.49; 17.60; 16.37; 17.64; 21.23 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep |
10.96; 14.24; 15.82; 14.09; 16.71; 19.75 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social |
7.99; 9.41; 9.89; 11.14; 11.19; 12.22 | 0.006 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS |
1.88; 1.95; 2.27; 2.10; 2.06; 2.57 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC) |
-0.84; -0.89; -1.05; -1.09; -1.08; -1.33 | <0.001 sig |
| SECONDARY Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT |
25.5; 23.4; 33.8; 30.5; 35.8; 34.0 | — |
| SECONDARY Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT |
12.9; 14.7; 18.0; 23.8; 26.8; 28.7 | — |
| SECONDARY Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility |
164; 164; 675; 15; 15; 56 | — |
| SECONDARY Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care |
223; 232; 906; 12; 9; 40 | — |
| SECONDARY Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities |
165; 160; 672; 13; 16; 65 | — |
| SECONDARY Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort |
120; 119; 495; 21; 19; 70 | — |
| SECONDARY Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression |
137; 142; 588; 22; 18; 68 | — |
| SECONDARY Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed |
-0.49; -0.59; -3.11; 0.39; -1.95; -3.74 | — |
| SECONDARY Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working |
-16.94; -12.97; -13.41; -19.16; -14.72; -16.68 | — |
| SECONDARY Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment |
-16.33; -12.09; -13.99; -17.83; -15.38; -17.27 | — |
| SECONDARY Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment |
-15.04; -16.25; -16.94; -16.85; -14.12; -18.91 | — |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT |
24.4; 39.9; 38.3; 40.1; 44.8; 49.6 | <0.001 sig |
| SECONDARY Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT |
63.7; 67.5; 72.8; 69.1; 71.3; 81.8 | <0.001 sig |
| SECONDARY Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT |
46.6; 53.8; 57.0; 53.6; 59.4; 64.6 | <0.001 sig |
| SECONDARY Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT |
46.7; 55.2; 62.0; 58.2; 67.0; 73.3 | <0.001 sig |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT |
17.2; 26.4; 27.9; 27.0; 35.1; 40.0 | <0.001 sig |
| SECONDARY Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT |
34.5; 29.3; 36.8; 36.7; 36.6; 46.6 | 0.002 sig |
| SECONDARY Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT |
53.0; 59.2; 64.1; 61.9; 65.7; 72.5 | <0.001 sig |
| SECONDARY Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT |
24.9; 28.2; 30.7; 31.3; 33.9; 42.8 | <0.001 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 Months 1, 3, 6, 9, 12 and EoT |
36.1; 46.6; 52.6; 47.8; 55.5; 65.1 | <0.001 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 HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT |
28.5; 36.6; 40.9; 39.6; 43.8; 52.3 | <0.001 sig |
| 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 Months 1, 3, 6, 9, 12 and EoT |
32.1; 37.1; 46.0; 43.3; 47.7; 57.6 | <0.001 sig |
| SECONDARY Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT |
29.9; 35.5; 42.8; 38.9; 44.8; 54.1 | <0.001 sig |
| SECONDARY Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT |
25.2; 29.0; 35.5; 33.3; 39.1; 45.9 | <0.001 sig |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume |
3.179; 4.549; 7.894; 4.686; 3.233; 7.033 | — |
Eligibility Criteria
Inclusion Criteria
Main Inclusion at Screening (Visit 1):
- Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months);
- Subject was willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
Main Inclusion at Randomization (Visit 2):
- Subject had a micturition frequency of on average ≥ 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition).
- Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period.
- Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period.
Exclusion Criteria
Main Exclusion at Screening (Visit 1):
- Subject had clinically significant bladder outflow obstruction at risk of urinary retention;
- Subject had significant PVR volume (> 150 mL);
- Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor;
- Subject has an indwelling catheter or practices intermittent self-catheterization;
- Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
- Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
Main Exclusion at Randomization (Visit 2):
- Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite).
- Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.
Data sourced from ClinicalTrials.gov (NCT02045862). 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.