Phase 3
Completed N=1,987
Study to Assess the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder
Urinary Bladder, Overactive
Source: ClinicalTrials.gov NCT00689104 ↗
Enrolled (actual)
1,987
Serious AEs
2.3%
Results posted
Oct 2012
Primary outcomePrimary: Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours — -1.17; -1.57; -1.46; -1.27 Incontinence episodes — p=0.003
Summary
The study is intended to test efficacy, safety and tolerability of two doses of Mirabegron against placebo and compare the efficacy and safety with active comparator in patients with symptoms of overactive bladder.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours |
-1.17; -1.57; -1.46; -1.27 | 0.003 sig |
| PRIMARY Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours |
-1.34; -1.93; -1.77; -1.59 | <0.001 sig |
| SECONDARY Change From Baseline to Final Visit in Mean Volume Voided Per Micturition |
12.3; 24.2; 25.6; 25.0 | <0.001 sig |
| SECONDARY Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours |
-0.65; -1.04; -1.03; -1.00 | 0.002 sig |
| SECONDARY Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours |
-0.77; -1.16; -1.29; -1.10 | 0.004 sig |
| SECONDARY Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours |
-1.00; -1.29; -1.40; -1.02; -1.18; -1.62 | — |
| SECONDARY Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours |
-1.15; -1.64; -1.66; -1.43; -1.33; -2.02 | — |
| SECONDARY Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition |
9.8; 20.1; 20.3; 21.4; 11.7; 20.7 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours |
-0.63; -0.98; -1.00; -1.01; -0.94; -1.27 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours |
-0.89; -1.39; -1.54; -1.63; -1.28; -1.90 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency |
-0.08; -0.19; -0.21; -0.21; -0.16; -0.26 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours |
-0.25; -0.27; -0.34; -0.29; -0.30; -0.41 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours |
-0.45; -0.73; -0.81; -0.67; -0.72; -1.02 | — |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit |
28.9; 32.1; 32.0; 33.4; 34.3; 42.6 | — |
| SECONDARY Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit |
46.0; 57.3; 54.4; 56.5; 53.9; 67.9 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score |
-9.7; -13.0; -13.8; -13.8; -13.3; -17.8 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score |
8.8; 9.5; 11.2; 9.4; 11.9; 13.7 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed |
-0.2; -1.9; -1.7; -1.2; -0.2; -1.8 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working |
-8.3; -12.5; -10.8; -6.7; -8.1; -12.8 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment |
-7.9; -13.2; -11.6; -5.8; -7.7; -13.6 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment |
-11.2; -15.0; -14.5; -14.7; -11.0; -14.9 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score |
334; 340; 334; 330; 27; 26 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score |
437; 445; 439; 432; 7; 9 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score |
298; 316; 327; 283; 25; 18 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score |
210; 211; 209; 197; 36; 32 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score |
219; 224; 232; 217; 37; 30 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) |
3.1; 3.3; 4.4; 3.2; 4.5; 5.5 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) |
-0.8; -1.1; -0.1; -1.0; -0.8; -1.0 | — |
| SECONDARY Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS) |
1.92; 2.57; 2.67; 2.44; 1.89; 2.55 | — |
| SECONDARY Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician |
-0.0; -0.0; -0.0; 0.0; -0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit |
56.9; 61.5; 62.7; 65.2; 56.6; 61.3 | — |
Eligibility Criteria
Inclusion Criteria
- Subject is willing and able to complete the micturition diary and questionnaires correctly
- Subject has symptoms of overactive bladder (urinary frequency and urgency with or without urge incontinence) for ≥ 3 months
- Subject experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period
- Subject must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence, during the 3-day micturition diary period
Exclusion Criteria
- Subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential, sexually active and not practicing a highly reliable method of birth control
- Subject has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor
- Subject has an indwelling catheter or practices intermittent self-catheterization
- Subject has diabetic neuropathy
- Subject has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
- Subject receives non-drug treatment including electro-stimulation therapy
- Subject has severe hypertension
- Subject has a known or suspected hypersensitivity to tolterodine, other anticholinergics, YM178, other beta-adrenoreceptor (ß-AR) agonists, or lactose or any of the other inactive ingredients
- Subject has been treated with any investigational drug or device within 30 days (90 days in the UK)
- Subject had an average total daily urine volume > 3000 mL as recorded in the 3-day micturition diary period
- Subject has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or gamma glutamyl transferase (γ-GT) > 3x ULN
- Subject has a clinically significant abnormal electrocardiogram (ECG)
Data sourced from ClinicalTrials.gov (NCT00689104). 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.