Urinary Bladder, OveractivePhase 2NCT01314872

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

A Phase 2 study testing Vibegron and Tolterodine ER in people with Urinary Bladder, Overactive, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Urinary Bladder, Overactive
What is being tested?: Vibegron and Tolterodine ER
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,395 participants
Where: No sites listed yet
Study dates: 31 Mar 2011to 10 Oct 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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

About this study

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

Read the 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
Being tested: Vibegron, Tolterodine ER, Placebo matching vibegron, Placebo matching tolterodine ER
Keywords: Overactive bladder, MK-4618, tolterodine
Medical subject headings: Urinary Bladder, Overactive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VibegronDrug
Also called MK-4618
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 ERDrug
Also called Detrol®
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Placebo matching vibegronDrug
Participants received placebo matching vibegron tablets, taken orally each morning.
Placebo matching tolterodine ERDrug
Participants received placebo matching tolterodine ER capsule, taken orally each morning.

Study groups in NCT01314872
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Vibegron; Drug: Tolterodine ER

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Extension: up to 52 weeks

Secondary outcomes (7)

Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at 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.
Measured: Baseline and Week 8
Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at 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.
Measured: Baseline and Week 8
Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at 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.
Measured: Baseline and Week 8
Extension Study: Change From Baseline in Average Daily Micturitions at Week 52
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.
Measured: Baseline and Week 52 of Extension Study
Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52
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.
Measured: Baseline and Week 52 of Extension Study
Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52
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.
Measured: Baseline and Week 52 of Extension Study
Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52
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.
Measured: Baseline and Week 52 of Extension Study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Mar 201110 Oct 2013

First posted15 Mar 2011 (estimated)
Study start31 Mar 2011
Primary completion22 Oct 2012
Study completion10 Oct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Urinary Bladder, OveractiveStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 1,395 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01314872
Sponsor's protocol ID: 4618-008
Other IDs: 132241, 2010-022121-15, 2011-002533-18
Status last verified: Jan 2019
First submitted: 11 Mar 2011
Last updated: 4 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 30661513

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Examining the Effects of Intra-detrusor Botox at Time of HoLEP in Men With Overactive Bladder Symptoms
Urinary Incontinence, Overactive Bladder Syndrome
Recruiting
UCon Treatment of Overactive Bladder (OAB) in Males
Urinary Incontinence, Urge Incontinence
Active, not recruitingObservational study
Overactive Bladder Symptoms and Urinary Incontinence In Women With Rheumatoid Arthritis
Rheumatoid Arthritis, Rheumatoid Arthritis (RA)
RecruitingObservational study
Predictive Value of Inflammatory Biomarkers for Mirabegron Response in Women With Overactive Bladder
Overactive Bladder (OAB)

All Urinary Bladder, Overactive trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01314872
Acronym / sponsor ID: 4618-008
Conditions: Urinary Bladder, Overactive
Keywords: Overactive bladder, MK-4618, tolterodine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,395 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 31 Mar 2011 (actual)
Primary completion: 22 Oct 2012 (actual)
Study completion: 10 Oct 2013 (actual)
First posted: 15 Mar 2011 (estimated)
Results: Posted 17 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 15

Arm	Type	Receives
Part 1: placebo	Placebo comparator	Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks.
Part 1: vibegron 3 mg	Experimental	Drug: Vibegron, Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants 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.
Part 1: vibegron 15 mg	Experimental	Drug: Vibegron, Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants 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.
Part 1: vibegron 50 mg	Experimental	Drug: Vibegron, Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants 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.
Part 1: vibegron 100 mg	Experimental	Drug: Vibegron, Drug: Placebo matching tolterodine ERParticipants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
Part 1: tolterodine ER 4 mg	Active comparator	Drug: Tolterodine ER, Drug: Placebo matching vibegronParticipants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks.
Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg	Experimental	Drug: Vibegron, Drug: Tolterodine ER, Drug: Placebo matching tolterodine ERParticipants 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.
Part 2: placebo	Placebo comparator	Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
Part 2: vibegron 100 mg	Experimental	Drug: Vibegron, Drug: Placebo matching tolterodine ERParticipants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
Part 2: tolterodine ER 4 mg	Active comparator	Drug: Tolterodine ER, Drug: Placebo matching vibegronParticipants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 4 weeks.
Part 2: vibegron 100 mg + tolterodine ER 4 mg	Experimental	Drug: Vibegron, Drug: Tolterodine ERParticipants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks.
Extension Study: vibegron 50 mg	Experimental	Drug: Vibegron, Drug: Placebo matching vibegron, Drug: Placebo matching tolterodine ERParticipants 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.
Extension Study: vibegron 100 mg	Experimental	Drug: Vibegron, Drug: Placebo matching tolterodine ERParticipants 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.
Extension Study: tolterodine ER 4 mg	Experimental	Drug: Tolterodine ER, Drug: Placebo matching vibegronParticipants 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.
Extension Study: vibegron 100 mg + tolterodine ER 4 mg	Experimental	Drug: Vibegron, Drug: Tolterodine ERParticipants 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VibegronAlso: MK-4618Participants 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.	Drug	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 ERAlso: Detrol®Participants received one tolterodine ER 4 mg capsule, taken orally once a day.	Drug	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 vibegronParticipants received placebo matching vibegron tablets, taken orally each morning.	Drug	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 ERParticipants received placebo matching tolterodine ER capsule, taken orally each morning.	Drug	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

Primary outcome

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.
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.
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.
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.
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.

7 secondary outcomes

Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8
Time frame: Baseline and Week 8
Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8
Time frame: Baseline and Week 8
Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8
Time frame: Baseline and Week 8
Extension Study: Change From Baseline in Average Daily Micturitions at Week 52
Time frame: Baseline and Week 52 of Extension Study
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
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
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

Results and safety

Results posted to the registry on 17 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Placebo	141	131
Part 1: Vibegron 3 mg	144	138
Part 1: Vibegron 15 mg	134	128
Part 1: Vibegron 50 mg	150	143
Part 1: Vibegron 100 mg	149	142
Part 1: Tolterodine ER 4 mg	135	128
Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg	134	126
Part 2: Placebo	64	57
Part 2: Vibegron 100 mg	112	106
Part 2: Tolterodine ER 4 mg	122	118
Part 2: Vibegron 100 mg + Tolterodine ER 4 mg	110	107
Extension Study: Vibegron 50 mg	0	0
Extension Study: Vibegron 100 mg	0	0
Extension Study: Tolterodine ER 4 mg	0	0
Extension Study: Vibegron 100 mg + Tolterodine ER 4 mg	0	0

Primary outcome: Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8

Time frame: Baseline and Week 8. Least squares mean (95% Confidence Interval). Unit: Micturitions

Measure	Part 1: Placebo n = 141	Part 1: Vibegron 3 mg n = 144	Part 1: Vibegron 15 mg n = 132	Part 1: Vibegron 50 mg n = 148	Part 1: Vibegron 100 mg n = 148	Part 1: Tolterodine ER 4 mg n = 134	Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg n = 134
Value	-1.16 (-1.5 to -0.82)	-1.62 (-1.95 to -1.29)	-1.61 (-1.96 to -1.27)	-1.80 (-2.13 to -1.47)	-2.07 (-2.40 to -1.74)	-1.71 (-2.05 to -1.36)	-2.05 (-2.40 to -1.70)

Part 1: Placebo vs Part 1: Vibegron 3 mg: Difference in least squares (LS) means: -0.46 (95% CI -0.92 to 0.01), p = 0.056, Constrained Longitudinal Data Analysis
Part 1: Placebo vs Part 1: Vibegron 15 mg: Difference in LS means: -0.45 (95% CI -0.93 to 0.03), p = 0.064, Constrained Longitudinal Data Analysis
Part 1: Placebo vs Part 1: Vibegron 50 mg: Difference in LS means: -0.64 (95% CI -1.11 to -0.18), p = 0.007, Constrained Longitudinal Data Analysis

Population analysed: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint.

Primary outcome: 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.. Number. Unit: Participants

Measure	Part 1: Placebo n = 141	Part 1: Vibegron 3 mg n = 144	Part 1: Vibegron 15 mg n = 134	Part 1: Vibegron 50 mg n = 148	Part 1: Vibegron 100 mg n = 149	Part 1: Tolterodine ER 4 mg n = 135	Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg n = 134	Part 2: Placebo n = 64	Part 2: Vibegron 100 mg n = 112	Part 2: Tolterodine ER 4 mg n = 122	Part 2: Vibegron 100 mg + Tolterodine ER 4 mg n = 110
Value	66	55	70	62	70	68	69	22	37	48	40

Population analysed: All participants as treated population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.

Primary outcome: 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. Number. Unit: Participants

Measure	Part 1: Placebo n = 141	Part 1: Vibegron 3 mg n = 144	Part 1: Vibegron 15 mg n = 134	Part 1: Vibegron 50 mg n = 148	Part 1: Vibegron 100 mg n = 149	Part 1: Tolterodine ER 4 mg n = 135	Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg n = 134	Part 2: Placebo n = 64	Part 2: Vibegron 100 mg n = 112	Part 2: Tolterodine ER 4 mg n = 122	Part 2: Vibegron 100 mg + Tolterodine ER 4 mg n = 110
Value	3	3	4	2	2	4	3	2	4	0	2

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

Time frame: Extension: up to 54 weeks (including 2-week follow-up). Number. Unit: Participants

Measure	Extension Study: Vibegron 50 mg n = 223	Extension Study: Vibegron 100 mg n = 248	Extension Study: Tolterodine ER 4 mg n = 240	Extension Study: Vibegron 100 mg + Tolterodine ER 4 mg n = 134
Value	134	157	158	82

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Part 1: up to approximately 10 weeks (including 2 week follow-up unless entering extension); Part 2: up to approximately 6 weeks (including 2 week follow-up unless entering extension); Extension: up to approximately 54 weeks (including 2 week follow-up). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Placebo	2 of 141 (1.4%)	32 of 141 (22.7%)	Not reported
Part 1: Vibegron 3 mg	1 of 144 (0.7%)	21 of 144 (14.6%)	Not reported
Part 1: Vibegron 15 mg	0 of 134 (0%)	27 of 134 (20.1%)	Not reported
Part 1: Vibegron 50 mg	1 of 148 (0.7%)	30 of 148 (20.3%)	Not reported
Part 1: Vibegron 100 mg	0 of 149 (0%)	33 of 149 (22.1%)	Not reported
Part 1: Tolterodine ER 4 mg	1 of 135 (0.7%)	33 of 135 (24.4%)	Not reported
Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg	1 of 134 (0.7%)	27 of 134 (20.1%)	Not reported
Part 2: Placebo	0 of 64 (0%)	6 of 64 (9.4%)	Not reported
Part 2: Vibegron 100 mg	0 of 112 (0%)	5 of 112 (4.5%)	Not reported
Part 2: Tolterodine ER 4 mg	2 of 122 (1.6%)	21 of 122 (17.2%)	Not reported
Part 2: Vibegron 100 mg + Tolterodine ER 4 mg	0 of 110 (0%)	20 of 110 (18.2%)	Not reported
Extension Study: Vibegron 50 mg	14 of 223 (6.3%)	59 of 223 (26.5%)	Not reported
Extension Study: Vibegron 100 mg	8 of 248 (3.2%)	73 of 248 (29.4%)	Not reported
Extension Study: Tolterodine ER 4 mg	18 of 240 (7.5%)	70 of 240 (29.2%)	Not reported
Extension Study: Vibegron 50 mg + Tolterodine ER 4 mg	1 of 134 (0.7%)	38 of 134 (28.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 30661513Mitcheson 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vibegron and Tolterodine ER in people with Urinary Bladder, Overactive, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 (time frame: Baseline and Week 8). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01314872, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2019.