Clinical trial NCT01314872: A Study of the Efficacy and Safety of Vibegron (MK-4618) in Participants With Overactive Bladder (OAB) (MK-4618-008)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urinary Bladder, Overactive
Keywords: Overactive bladder
MK-4618
tolterodine
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-03-15
Enrollment: 1395
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8
timeFrame: Baseline and Week 8
measure: Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: 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.
measure: Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE
timeFrame: Part 1: up to 8 weeks; Part 2: up to 4 weeks
measure: Extension Study: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Extension: up to 54 weeks (including 2-week follow-up)
measure: Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE
timeFrame: Extension: up to 52 weeks
Secondary outcomes:
measure: Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8
timeFrame: Baseline and Week 8
measure: Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8
timeFrame: Baseline and Week 8
measure: Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8
timeFrame: Baseline and Week 8
measure: Extension Study: Change From Baseline in Average Daily Micturitions at Week 52
timeFrame: Baseline and Week 52 of Extension Study
measure: Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52
timeFrame: Baseline and Week 52 of Extension Study
measure: Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52
timeFrame: Baseline and Week 52 of Extension Study
measure: Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52
timeFrame: Baseline and Week 52 of Extension Study
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Mitcheson HD, Samanta S, Muldowney K, Pinto CA, Rocha BA, Green S, Bennett N, Mudd PN Jr, Frenkl TL. Vibegron (RVT-901/MK-4618/KRP-114V) Administered Once Daily as Monotherapy or Concomitantly with Tolterodine in Patients with an Overactive Bladder: A Multicenter, Phase IIb, Randomized, Double-blind, Controlled Trial. Eur Urol. 2019 Feb;75(2):274-282. doi: 10.1016/j.eururo.2018.10.006. Epub 2018 Oct 25.