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

• ClinicalTrials.gov Identifier: NCT01314872
• Recruitment Status: Completed
• First Posted: March 15, 2011
• Results First Posted: June 17, 2016
• Last Update Posted: February 4, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Urinary Bladder, Overactive	Drug: Vibegron; Drug: Tolterodine ER; Drug: Placebo matching vibegron; Drug: Placebo matching tolterodine ER	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1395 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 31, 2011
• Actual Primary Completion Date: October 22, 2012
• Actual Study Completion Date: October 10, 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 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.	Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Active Comparator: 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.	Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Placebo Comparator: Part 2: placebo; 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; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Active Comparator: 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.	Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Placebo matching tolterodine ER; Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Experimental: 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.	Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®; Drug: Placebo matching vibegron; Participants received placebo matching vibegron tablets, taken orally each morning.
Experimental: 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.	Drug: 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.; Other Name: MK-4618; Drug: Tolterodine ER; Participants received one tolterodine ER 4 mg capsule, taken orally once a day.; Other Name: Detrol®

Outcome Measures

Primary Outcome Measures :

1. Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 [ Time Frame: 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.
2. Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: 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.
3. Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE [ Time Frame: 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.
4. Extension Study: Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: 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.
5. Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE [ Time Frame: 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.

Secondary Outcome Measures :

1. Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 [ Time Frame: Baseline and Week 8 ]
   Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode 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 total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
2. Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 [ Time Frame: Baseline and Week 8 ]
   Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode 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 total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
3. Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 [ Time Frame: Baseline and Week 8 ]
   Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode 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 strong urge episodes that occurred during the week of placebo run-in prior to Week 0 visit.
4. Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ]
   Participants were required to keep a voiding diary, recording the daily occurrence of each micturition. The average daily number of micturitions was calculated as the total number of recorded micturitions that occurred during the 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
5. Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ]
   Participants were required to keep a voiding diary, recording the occurrence of each urge incontinence episode. The average daily number of urge incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
6. Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ]
   Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
7. Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ]
   Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01314872
• Other Study ID Numbers: 4618-008; 132241 ( Registry Identifier: JAPIC-CTI ); 2010-022121-15 ( EudraCT Number ); 2011-002533-18 ( EudraCT Number )
• First Posted: March 15, 2011
• Results First Posted: June 17, 2016
• Last Update Posted: February 4, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme Corp.:

Overactive bladder; MK-4618; tolterodine

Additional relevant MeSH terms:

Urinary Bladder, Overactive; Urinary Bladder Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Tolterodine Tartrate; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents