A Randomized, Double-Blind, Parallel Group, Active Controlled, Multi-center Long-term Study to Assess the Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) 50 mg qd and 100 mg qd in Subjects With Symptoms of Overactive Bladder
Overview
- Phase
- Phase 3
- Intervention
- Mirabegron
- Conditions
- Urinary Bladder, Overactive
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 2792
- Primary Endpoint
- Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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.
Detailed Description
Patients who completed 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909) or new patients could be enrolled in this study if eligible.
Investigators
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
Arms & Interventions
Mirabegron 50 mg
Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Intervention: Mirabegron
Mirabegron 50 mg
Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Intervention: Placebo to Tolterodine
Tolterodine ER 4 mg
Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Intervention: Tolterodine
Mirabegron 100 mg
Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.
Intervention: Mirabegron
Mirabegron 100 mg
Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.
Intervention: Placebo to Tolterodine
Tolterodine ER 4 mg
Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Intervention: Placebo to Mirabegron
Outcomes
Primary Outcomes
Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs)
Time Frame: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.
An adverse event (AE) was defined as any untoward medical occurrence in a patient administered a study drug and which did not necessarily have a causal relationship with the treatment. The investigator assessed the severity of each AE, including abnormal laboratory values, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities.
Secondary Outcomes
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition(Baseline and Months 1, 3, 6, 9 and 12)
- Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit(Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score(Baseline and Months 1, 3, 6, 9 and 12)
- 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(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS)(Baseline and Month 12)
- Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)(Baseline and Month 12)
- Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed(Baseline and Months 3, 6 and 12)
- Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working(Baseline and Months 3, 6 and 12)
- Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment(Baseline and Months 3, 6 and 12)
- Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment(Baseline and Months 3, 6 and 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score(Baseline and Month 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score(Baseline and Month 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score(Baseline and Month 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score(Baseline and Month 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score(Baseline and Month 12)
- 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)(Baseline and Months 1, 3, 6, 9 and 12)
- Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician(Baseline and Months 3, 6 and 12)
- Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC)(Baseline and Month 12)
- Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram(From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.)