A Phase IIb Randomized, Placebo- and Active Comparator (Tolterodine)-Controlled, 2-Part Clinical Study of the Efficacy and Safety of MK-4618 in Patients With Overactive Bladder A 52-week Extension to: A Phase IIb Randomized, Placebo- and Active Comparator (Tolterodine)-Controlled, 2-Part Clinical Study of the Efficacy and Safety of MK-4618 in Patients With Overactive Bladder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,395
- 主要终点
- Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE
研究概览
简要总结
This is a 2-part study to assess if vibegron (MK-4618) reduces the number of daily urinations more effectively than placebo in participants with overactive bladder (OAB). The primary hypothesis of the base study is that administration of vibegron demonstrates a dose-related reduction, compared with placebo, in average number of daily micturitions in participants with OAB after 8 weeks of treatment.
详细描述
All participants received placebo (run-in) for 1 week prior to randomization to Parts 1 and 2. Participants who complete the base study may be screened for a year-long, multicenter extension for assessment of long-term safety and efficacy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •If participant is of reproductive potential, must agree to remain abstinent or use (or have his/her partner use) 2 acceptable methods of birth control within the projected duration of the study
- •Clinical history of OAB for at least 3 months and meets either the OAB wet or OAB dry criteria
- •Is able to read, understand and complete questionnaires and voiding diaries without assistance
- •Is ambulatory and in good general physical and mental health
- •No clinically significant electrocardiogram or laboratory abnormality
排除标准
- •If female, is currently pregnant or breast-feeding, or expecting to conceive within the projected duration of the study
- •Evidence of diabetes insipidus, uncontrolled hyperglycemia or uncontrolled hypercalcemia
- •Allergy, intolerance, or history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of tolterodine ER or vibegron (MK-4618) formulation; or has a history or active diagnosis of any condition contraindicated in the tolterodine ER prescribing label
- •Has lower urinary tract pathology that could be responsible for urgency, frequency, or incontinence
- •History of injury, surgery, or neurodegenerative diseases (e.g., multiple sclerosis) that could affect the lower urinary tract or its nerve supply
- •History of continual urine leakage
- •Surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months
- •Known history of elevated postvoid residual
- •Bladder training or electrostimulation within 2 weeks or is planning to initiate either procedure during the study
- •Active or recurrent (>6 episodes per year) urinary tract infections
- •Current hematuria
- •Required use of an indwelling catheter or requires intermittent catheterization
- •History of fecal incontinence
研究组 & 干预措施
Part 1: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 1: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 1: vibegron 3 mg
Participants received one vibegron 3 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Vibegron (Drug)
Part 1: vibegron 3 mg
Participants received one vibegron 3 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 1: vibegron 3 mg
Participants received one vibegron 3 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 1: vibegron 15 mg
Participants received one vibegron 15 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Vibegron (Drug)
Part 1: vibegron 15 mg
Participants received one vibegron 15 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 1: vibegron 15 mg
Participants received one vibegron 15 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 1: vibegron 50 mg
Participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Vibegron (Drug)
Part 1: vibegron 50 mg
Participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 1: vibegron 50 mg
Participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 1: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Vibegron (Drug)
Part 1: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 1: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks.
干预措施: Tolterodine ER (Drug)
Part 1: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg
Participants received one vibegron 50 mg tablet and one placebo matching vibegron tablet, taken orally each morning, for 8 weeks. They also received one tolterodine ER 4 mg capsule for the first 4 weeks and one placebo matching tolterodine ER capsule for the second 4 weeks, both taken orally each morning.
干预措施: Vibegron (Drug)
Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg
Participants received one vibegron 50 mg tablet and one placebo matching vibegron tablet, taken orally each morning, for 8 weeks. They also received one tolterodine ER 4 mg capsule for the first 4 weeks and one placebo matching tolterodine ER capsule for the second 4 weeks, both taken orally each morning.
干预措施: Tolterodine ER (Drug)
Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg
Participants received one vibegron 50 mg tablet and one placebo matching vibegron tablet, taken orally each morning, for 8 weeks. They also received one tolterodine ER 4 mg capsule for the first 4 weeks and one placebo matching tolterodine ER capsule for the second 4 weeks, both taken orally each morning.
干预措施: Placebo matching tolterodine ER (Drug)
Part 2: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 2: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 2: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
干预措施: Vibegron (Drug)
Part 2: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Part 2: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 4 weeks.
干预措施: Tolterodine ER (Drug)
Part 2: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 4 weeks.
干预措施: Placebo matching vibegron (Drug)
Part 2: vibegron 100 mg + tolterodine ER 4 mg
Participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks.
干预措施: Vibegron (Drug)
Part 2: vibegron 100 mg + tolterodine ER 4 mg
Participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks.
干预措施: Tolterodine ER (Drug)
Extension Study: vibegron 50 mg
Participants in Base Study/Part 1 who received vibegron 50 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 3 mg received vibegron 50 mg in the Extension Study. Also, participants in Base Study/Part 1 who received vibegron 50 mg + tolterodine ER for 4 weeks, followed by vibegron 50 mg alone for 4 weeks, remained on vibegron 50 mg in the Extension Study. In the extension, participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
干预措施: Vibegron (Drug)
Extension Study: vibegron 50 mg
Participants in Base Study/Part 1 who received vibegron 50 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 3 mg received vibegron 50 mg in the Extension Study. Also, participants in Base Study/Part 1 who received vibegron 50 mg + tolterodine ER for 4 weeks, followed by vibegron 50 mg alone for 4 weeks, remained on vibegron 50 mg in the Extension Study. In the extension, participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
干预措施: Placebo matching vibegron (Drug)
Extension Study: vibegron 50 mg
Participants in Base Study/Part 1 who received vibegron 50 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 3 mg received vibegron 50 mg in the Extension Study. Also, participants in Base Study/Part 1 who received vibegron 50 mg + tolterodine ER for 4 weeks, followed by vibegron 50 mg alone for 4 weeks, remained on vibegron 50 mg in the Extension Study. In the extension, participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Extension Study: vibegron 100 mg
Participants in Base Study/Part 1 or Part 2 who received vibegron 100 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 15 mg received vibegron 100 mg in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
干预措施: Vibegron (Drug)
Extension Study: vibegron 100 mg
Participants in Base Study/Part 1 or Part 2 who received vibegron 100 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 15 mg received vibegron 100 mg in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
干预措施: Placebo matching tolterodine ER (Drug)
Extension Study: tolterodine ER 4 mg
Participants in Base Study/Part 1 or Part 2 who received tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received placebo also received tolterodine ER 4 mg in the Extension Study. In the extension, participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 52 weeks.
干预措施: Tolterodine ER (Drug)
Extension Study: tolterodine ER 4 mg
Participants in Base Study/Part 1 or Part 2 who received tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received placebo also received tolterodine ER 4 mg in the Extension Study. In the extension, participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 52 weeks.
干预措施: Placebo matching vibegron (Drug)
Extension Study: vibegron 100 mg + tolterodine ER 4 mg
Participants in Base Study/Part 1 who received vibegron 100 mg + tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 2 who received placebo were assigned to the vibegron 100 mg + tolterodine ER 4 mg arm in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 52 weeks.
干预措施: Vibegron (Drug)
Extension Study: vibegron 100 mg + tolterodine ER 4 mg
Participants in Base Study/Part 1 who received vibegron 100 mg + tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 2 who received placebo were assigned to the vibegron 100 mg + tolterodine ER 4 mg arm in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 52 weeks.
干预措施: Tolterodine ER (Drug)
结局指标
主要结局
Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE
时间窗: Extension: up to 52 weeks
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Extension Study: Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Extension: up to 54 weeks (including 2-week follow-up)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8
时间窗: Baseline and Week 8
Participants were required to keep a voiding diary, recording the occurrence of each micturition. The average daily number of micturitions was calculated as the total number of micturitions that occurred over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of daily micturitions that occurred during the week of placebo run-in prior to Week 0 visit.
Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Part 1: up to 8 weeks; Part 2: up to 4 weeks. The time frame was an additional 2 weeks for participants not continuing to the Extension Study.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE
时间窗: Part 1: up to 8 weeks; Part 2: up to 4 weeks
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
次要结局
- Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8(Baseline and Week 8)
- Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8(Baseline and Week 8)
- Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8(Baseline and Week 8)
- Extension Study: Change From Baseline in Average Daily Micturitions at Week 52(Baseline and Week 52 of Extension Study)
- Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52(Baseline and Week 52 of Extension Study)
- Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52(Baseline and Week 52 of Extension Study)
- Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52(Baseline and Week 52 of Extension Study)