Phase 3
Completed N=2,452
Study to Test the Long Term Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder
Urinary Bladder, Overactive
Source: ClinicalTrials.gov NCT00688688 ↗
Enrolled (actual)
2,452
Serious AEs
5.6%
Results posted
Oct 2012
Primary outcomePrimary: Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) — 222; 240; 251; 212 participants
Summary
The study is intended to test the safety, tolerability, efficacy of two doses of long term once daily (qd) treatment of Mirabegron in patients with symptoms of overactive bladder and secondly to compare these with active comparator.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) |
222; 240; 251; 212; 211; 218 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours |
-0.94; -1.10; -1.02; -1.13; -1.46; -1.27 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours |
-0.94; -1.03; -0.96; -1.10; -1.28; -1.09 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition |
12.1; 16.7; 16.0; 14.8; 20.4; 17.4 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours |
-0.92; -1.04; -0.95; -1.05; -1.23; -1.06 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours |
-1.30; -1.31; -1.11; -1.37; -1.83; -1.55 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency |
-0.18; -0.19; -0.17; -0.21; -0.28; -0.24 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours |
-0.75; -0.79; -0.79; -0.80; -0.94; -0.95 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours |
-0.26; -0.29; -0.29; -0.41; -0.45; -0.37 | — |
| SECONDARY Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit |
35.4; 36.7; 33.4; 40.9; 45.4; 39.2 | — |
| SECONDARY Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit |
58.2; 57.0; 56.3; 61.7; 66.1; 61.5 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score |
-10.5; -12.5; -11.5; -13.4; -16.1; -13.5 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score |
7.7; 8.9; 8.9; 9.9; 11.9; 10.6 | — |
| SECONDARY Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) |
-0.8; -0.9; -0.9; -0.8; -0.9; -0.8 | — |
| SECONDARY Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS) |
2.27; 2.27; 2.52; 2.08; 2.11; 2.27 | — |
| SECONDARY Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed |
-0.06; -1.0; -0.6; -1.3; -1.5; -0.7 | — |
| SECONDARY Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working |
-10.6; -9.9; -10.9; -13.0; -11.9; -11.1 | — |
| SECONDARY Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment |
-11.4; -10.9; -11.0; -12.4; -13.0; -11.1 | — |
| SECONDARY Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment |
-12.0; -13.7; -12.3; -14.0; -15.6; -13.4 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score |
567; 601; 573; 36; 42; 39 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score |
718; 735; 720; 16; 15; 23 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score |
536; 569; 542; 40; 55; 53 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score |
398; 396; 398; 54; 69; 63 | — |
| SECONDARY Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score |
413; 453; 429; 43; 34; 43 | — |
| SECONDARY Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) |
3.8; 3.9; 3.1; 5.0; 5.4; 4.3 | — |
| SECONDARY Change From Baseline to Months 3, 6, 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) |
55.7; 60.6; 56.6; 52.9; 59.6; 54.4 | — |
| SECONDARY Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram |
485; 503; 508; 213; 192; 224 | — |
Eligibility Criteria
Inclusion Criteria
- Patient is willing and able to complete the micturition diary and questionnaires correctly
- Patient has symptoms of overactive bladder for ≥ 3 months
- Patient experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period
- Patient 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
- Patient 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
- Patient has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor
- Patient has an indwelling catheter or practices intermittent self-catheterization
- Patient has diabetic neuropathy
- Patient 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
- Patient receives non-drug treatment including electro-stimulation therapy
- Patient has severe hypertension
- Patient 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
- Patient has been treated with any investigational drug or device within 30 days (90 days in the UK for all clinical studies except 178-CL-046)
- Patient had an average total daily urine volume > 3000 mL as recorded in the 3-day micturition diary period
- Patient has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or gamma-glutamyl transpeptidase (γ-GT) > 3x ULN
- Patient has a clinically significant abnormal electrocardiogram (ECG)
Data sourced from ClinicalTrials.gov (NCT00688688). 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.