A Randomized, Double-Blind, Parallel Group, Placebo and Active Controlled, Multicenter Study to Assess the Efficacy and Safety of Mirabegron in Subjects With Symptoms of Overactive Bladder
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,336
- 主要终点
- Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Mirabegron 100 mg
Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.
干预措施: Placebo to Tolterodine (Drug)
Tolterodine SR 4 mg
Participants received tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.
干预措施: Placebo to Mirabegron (Drug)
Mirabegron 50 mg
Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.
干预措施: Placebo to Tolterodine (Drug)
Placebo
Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
干预措施: Placebo to Tolterodine (Drug)
Placebo
Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
干预措施: Placebo to Mirabegron (Drug)
Mirabegron 50 mg
Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.
干预措施: Mirabegron (Drug)
Mirabegron 100 mg
Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.
干预措施: Mirabegron (Drug)
Tolterodine SR 4 mg
Participants received tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.
干预措施: Tolterodine (Drug)
结局指标
主要结局
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours
时间窗: Baseline and Week 12 (final visit)
The average number of incontinence episodes (any involuntary leakage of urine) per day was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days before the Baseline and Week 12 clinic visits. Least Squares (LS) Means were generated from an analysis of covariance (ANCOVA) model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours
时间窗: Baseline and Week 12
The average number of micturitions (urinations) per 24 hours was derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days before the Baseline and Week 12 clinic visits. LS Means generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.
次要结局
- Change From Baseline to Final Visit in Mean Volume Voided Per Micturition(Baseline and Week 12)
- Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Week 4)
- Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours(Baseline and Week 4)
- Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Weeks 8 and 12)
- Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours(Baseline and Weeks 8 and 12)
- Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours(Baseline and Weeks 4, 8 and 12)
- 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(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours(Baseline and Weeks 4, 8 and 12)
- Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit(Weeks 4, 8 and 12)
- Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed(Baseline and Week 12)
- Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working(Baseline and Week 12)
- Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment(Baseline and Week 12)
- Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment(Baseline and Week 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score(Baseline and Week 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score(Baseline and Week 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score(Baseline and Week 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score(Baseline and Week 12)
- Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score(Baseline and Week 12)
- 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)(Baseline and Weeks 4, 8 and 12)
- Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)(Baseline and Week 12)
- Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS)(Baseline and Week 12)
- Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician(Baseline and Weeks 4, 8 and 12)
- Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit(Baseline and Week 12)