NCT01340027已完成2 期
A Randomized, Double-Blind, Factorial, Parallel-Group, Active and Placebo-Controlled, Multicenter Dose-Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Six Dose Combinations of Solifenacin Succinate and Mirabegron Compared to Mirabegron and Solifenacin Succinate Monotherapies in the Treatment of Overactive Bladder.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,307
- 试验地点
- 133
- 主要终点
- Change From Baseline to End of Treatment (EOT) in Mean Volume Voided Per Micturition
研究概览
简要总结
The purpose of this study is to examine how well two medicines in combination (solifenacin succinate and mirabegron) work in the treatment of bladder problems over a 12-week period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, 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
- •Inclusion Criteria at Visit 1/Screening:
- •Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m^2 and a total body weight between 50 and 95 kg;
- •Subject is willing and able to complete the micturition diary and questionnaires correctly and is willing 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;
- •Subject has symptoms of overactive bladder (OAB; urinary frequency, urgency and/or urgency incontinence) for at least 3 months.
- •Inclusion Criteria at Visit 3/Baseline:
- •Subject has experienced frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period (incontinence episode should not be counted as a micturition);
- •Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour period (with or without urgency incontinence) during the 3 day micturition diary period.
排除标准
- •Exclusion Criteria at Visit 1/Screening:
- •Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (Beta Human Chorionic Gonadotropin in serum) at Screening must be negative in women of childbearing potential;
- •Female subjects of childbearing potential and not using a highly effective method of birth control during the study and for 30 days after final study drug administration.
- •Male subjects (unless surgically sterile) with female spouses/partners who are of childbearing potential, and not using a barrier method of contraception during the study and for 30 days after final study drug administration. In addition, female spouses/partners of male subjects and who are of childbearing potential should also use a highly effective method of birth control during the study and for 30 days after final study drug administration. Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
- •Subject has significant post-void residual (PVR) volume (> 150 mL);
- •Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by the cough provocation test);
- •Subject has a neurological cause for detrusor overactivity;
- •Subject has an indwelling catheter or practices intermittent self-catheterization;
- •Subject has diabetic neuropathy;
- •Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
- •Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
- •Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
- •Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis or Crohn's Disease, toxic megacolon, myasthenia gravis or any other condition which makes the use of anticholinergics contraindicated;
- •Subject has clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to Screening, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure and stroke;
- •Subject is receiving current non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to Screening);
- •Subject is using medications intended to treat OAB or prohibited medications.
- •Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their excipients;
- •Subject has any significant neurological disease or defect affecting bladder function (e.g., neurogenic bladder, systemic or central neurological disease such as multiple sclerosis [MS] and Parkinson's disease);
- •Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg;
- •Exclusion Criteria at Visit 2/Placebo Run-In:
- •Subject has evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL). The subject can be enrolled into the study after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture). However, the subject must be re screened if the initial screening visit was > 28 days;
- •Subject has a QT interval > 450 ms or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia) or is on drug treatment known to be associated with QT prolongation;
- •Subject has clinically significant abnormalities on the 12 lead electrocardiogram (ECG);
- •Subject has serum creatinine > 150 µmol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal (ULN), gamma-glutamyltransferase (γ-GT) > 3x ULN, or total bilirubin > 2x ULN, as assessed in Screening samples;
- •Exclusion Criteria at Visit 3/Baseline:
- •Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period;
- •Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants received matching placebo tablets orally once a day for 12 weeks
干预措施: Placebo (Drug)
Mirabegron 25 mg
Active Comparator
Participants received mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Mirabegron 50 mg
Active Comparator
Participants received mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 2.5 mg
Active Comparator
Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 5 mg
Active Comparator
Participants received solifenacin 5 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 10 mg
Active Comparator
Participants received solifenacin 10 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 2.5 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 2.5 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 2.5 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 2.5 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 5 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 5 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 5 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 5 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 10 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 10 mg and Mirabegron 25 mg
Experimental
Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
Solifenacin 10 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Mirabegron (Drug)
Solifenacin 10 mg and Mirabegron 50 mg
Experimental
Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks
干预措施: Solifenacin succinate (Drug)
结局指标
主要结局
Change From Baseline to End of Treatment (EOT) in Mean Volume Voided Per Micturition
时间窗: Baseline and Week 12
The average volume voided per micturition was calculated from the volume of each micturition measured by the participant and recorded in a micturition diary for 3 days before the Baseline and Week 12 clinic visits.
次要结局
- Change From Baseline to Each Visit in Mean Volume Voided Per Micturition(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Week 12)
- Change From Baseline to Each Visit in Mean Number of Micturitions Per 24 Hours(Baseline and Weeks 2, 4, 8 and 12)
- Percentage of Participants With Zero Incontinence Episodes Post-baseline(Weeks 2, 4, 8 and 12)
- Percentage of Participants With 50% Reduction in Incontinence Episodes(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to Each Visit in Mean Number of Nocturia Episodes Per 24-Hours(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to Each Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours(Baseline and Weeks 2, 4, 8 and 12)
- Percentage of Participants With Deterioration in PPBC(Baseline and Week 12)
- Change From Baseline to End of Treatment in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q)(Baseline and Week 12)
- Percentage of Participants With a Symptom Bother Response(Baseline and Week 12)
- Change From Baseline to End of Treatment in Health-related Quality of Life (HRQL) Total Score(Baseline and Week 12)
- Change From Baseline to End of Treatment in European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)(Baseline and Week 12)
- Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours(Baseline and Week 12)
- Percentage of Participants With a Micturition Response(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to Each Visit in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to Each Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours(Baseline and Weeks 2, 4, 8 and 12)
- Percentage of Participants With a Health-related Quality of Life Total Score Response(Baseline and Week 12)
- Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score(Baseline and Week 12)
- Change From Baseline to Each Visit in Mean Level of Urgency(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to Each Visit in Mean Number of Pads Used Per 24 Hours(Baseline and Weeks 2, 4, 8 and 12)
- Change From Baseline to End of Treatment in Patient Perception of Bladder Condition (PPBC)(Baseline and Week 12)
- Percentage of Participants With Improvement in PPBC(Baseline and Week 12)
- Change From Baseline to End of Treatment in Treatment Satisfaction on Visual Analog Scale (TS-VAS)(Baseline and Week 12)
- Percentage of Participants With Major Improvement in PPBC(Baseline and Week 12)
- Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score(Baseline and Week 12)
- Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score(Baseline and Week 12)
- Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score(Baseline and Week 12)
- Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score(Baseline and Week 12)
- Change From Baseline to End of Treatment in Work Productivity and Activity Impairment (WPAI)(Baseline and Week 12)
研究者
研究点 (133)
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