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

NCT01314872 | Completed Phase 2 Results

• 4 other identifiers: 4618-0081322412010-022121-152011-002533-18
• Study Type: interventional
• Target: 1,395
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Urinary Bladder, Overactive

Keywords

Overactive bladder; MK-4618; tolterodine

Outcome Measures

Primary Outcomes (5)

• Base Study/Part 1: Change From Baseline in Average Daily Micturitions at 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.

  Baseline and Week 8

• Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE)

  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.

  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.

• Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE

  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.

  Part 1: up to 8 weeks; Part 2: up to 4 weeks

• Extension Study: Number of Participants Who Experienced an Adverse Event (AE)

  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: up to 54 weeks (including 2-week follow-up)

• Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE

  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: up to 52 weeks

Secondary Outcomes (7)

• 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 Total 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

Study Arms (15)

Part 1: placebo

PLACEBO COMPARATOR

Participants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks.

Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Part 1: vibegron 3 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Part 1: vibegron 15 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Part 1: vibegron 50 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Part 1: vibegron 100 mg

EXPERIMENTAL

Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.

Drug: Vibegron; Drug: Placebo matching tolterodine ER

Part 1: tolterodine ER 4 mg

ACTIVE COMPARATOR

Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks.

Drug: Tolterodine ER; Drug: Placebo matching vibegron

Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Tolterodine ER; Drug: Placebo matching tolterodine ER

Part 2: placebo

PLACEBO COMPARATOR

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

Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Part 2: vibegron 100 mg

EXPERIMENTAL

Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.

Drug: Vibegron; Drug: Placebo matching tolterodine ER

Part 2: tolterodine ER 4 mg

ACTIVE COMPARATOR

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

Drug: Tolterodine ER; Drug: Placebo matching vibegron

Part 2: vibegron 100 mg + tolterodine ER 4 mg

EXPERIMENTAL

Participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks.

Drug: Vibegron; Drug: Tolterodine ER

Extension Study: vibegron 50 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER

Extension Study: vibegron 100 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Placebo matching tolterodine ER

Extension Study: tolterodine ER 4 mg

EXPERIMENTAL

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.

Drug: Tolterodine ER; Drug: Placebo matching vibegron

Extension Study: vibegron 100 mg + tolterodine ER 4 mg

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Tolterodine ER

Interventions

Vibegron 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.

Also known as: MK-4618

Extension Study: vibegron 100 mg; Extension Study: vibegron 100 mg + tolterodine ER 4 mg; Extension Study: vibegron 50 mg; Part 1: vibegron 100 mg; Part 1: vibegron 15 mg; Part 1: vibegron 3 mg; Part 1: vibegron 50 mg; Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg; Part 2: vibegron 100 mg; Part 2: vibegron 100 mg + tolterodine ER 4 mg

Tolterodine ER DRUG

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

Also known as: Detrol®

Extension Study: tolterodine ER 4 mg; Extension Study: vibegron 100 mg + tolterodine ER 4 mg; Part 1: tolterodine ER 4 mg; Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg; Part 2: tolterodine ER 4 mg; Part 2: vibegron 100 mg + tolterodine ER 4 mg

Placebo matching vibegron DRUG

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

Extension Study: tolterodine ER 4 mg; Extension Study: vibegron 50 mg; Part 1: placebo; Part 1: tolterodine ER 4 mg; Part 1: vibegron 15 mg; Part 1: vibegron 3 mg; Part 1: vibegron 50 mg; Part 2: placebo; Part 2: tolterodine ER 4 mg

Placebo matching tolterodine ER DRUG

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

Extension Study: vibegron 100 mg; Extension Study: vibegron 50 mg; Part 1: placebo; Part 1: vibegron 100 mg; Part 1: vibegron 15 mg; Part 1: vibegron 3 mg; Part 1: vibegron 50 mg; Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg; Part 2: placebo; Part 2: vibegron 100 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30661513 RESULT

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

N-(4-((5-(hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo(1,2-a)pyrimidine-6-carboxamide; Tolterodine Tartrate

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2011
• First Posted: March 15, 2011
• Study Start: March 31, 2011
• Primary Completion: October 22, 2012
• Study Completion: October 10, 2013
• Last Updated: February 4, 2019
• Results First Posted: June 17, 2016

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share