A Study of the Efficacy and Safety of Vibegron (MK-4618) in Participants With Overactive Bladder (OAB) (MK-4618-008)

NCT ID: NCT01314872

Last Updated: 2019-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1395 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2013-10-10

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.

Conditions

Urinary Bladder, Overactive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: ACTIVE_COMPARATOR

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

Part 2: placebo

Participants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: ACTIVE_COMPARATOR

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Placebo matching tolterodine ER

Intervention Type: DRUG

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Placebo matching vibegron

Intervention Type: DRUG

Participants received placebo matching vibegron tablets, taken orally each morning.

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Tolterodine ER

Intervention Type: DRUG

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Interventions

Vibegron

Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.

Intervention Type: DRUG

Tolterodine ER

Participants received one tolterodine ER 4 mg capsule, taken orally once a day.

Intervention Type: DRUG

Placebo matching vibegron

Participants received placebo matching vibegron tablets, taken orally each morning.

Intervention Type: DRUG

Placebo matching tolterodine ER

Participants received placebo matching tolterodine ER capsule, taken orally each morning.

Intervention Type: DRUG

Other Intervention Names

MK-4618; Detrol®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 30661513 (View on PubMed)

Other Identifiers

132241

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-022121-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2011-002533-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

4618-008

Identifier Type: -

Identifier Source: org_study_id