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

Urinary Bladder, Overactive Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01314872
• Other study ID #: 4618-008
• Secondary ID: 1322412010-02212
• Status: Completed
• Phase: Phase 2
• Start date: March 31, 2011
• Est. completion date: October 10, 2013

Study information

• Verified date: January 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 number of daily micturitions in participants with OAB after 8 weeks of treatment.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1395
• Est. completion date: October 10, 2013
• Est. primary completion date: October 22, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Urinary Bladder, Overactive

Intervention

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.
• Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
• Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
• Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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 Mul — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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.
Primary	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
Primary	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)
Primary	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	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.	Baseline and Week 8
Secondary	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.	Baseline and Week 8
Secondary	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.	Baseline and Week 8
Secondary	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.	Baseline and Week 52 of Extension Study
Secondary	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.	Baseline and Week 52 of Extension Study
Secondary	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.	Baseline and Week 52 of Extension Study
Secondary	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.	Baseline and Week 52 of Extension Study