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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Urinary Bladder, Overactive

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01314872

2011-002533-18 (EudraCT Number)

2010-022121-15 (EudraCT Number)

132241 (Registry Identifier)

4618-008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,395 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,395 participants in 15 patient groups, including a placebo group

Part 1: placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Placebo matching vibegron

Part 1: vibegron 3 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Drug: Placebo matching vibegron

Part 1: vibegron 15 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Drug: Placebo matching vibegron

Part 1: vibegron 50 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Drug: Placebo matching vibegron

Part 1: vibegron 100 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Part 1: tolterodine ER 4 mg

Active Comparator group

Description:

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

Treatment:

Drug: Placebo matching vibegron

Drug: Tolterodine ER

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Drug: Tolterodine ER

Part 2: placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Placebo matching vibegron

Part 2: vibegron 100 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Part 2: tolterodine ER 4 mg

Active Comparator group

Description:

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

Treatment:

Drug: Placebo matching vibegron

Drug: Tolterodine ER

Part 2: vibegron 100 mg + tolterodine ER 4 mg

Experimental group

Description:

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

Treatment:

Drug: Vibegron

Drug: Tolterodine ER

Extension Study: vibegron 50 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Drug: Placebo matching vibegron

Extension Study: vibegron 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching tolterodine ER

Drug: Vibegron

Extension Study: tolterodine ER 4 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching vibegron

Drug: Tolterodine ER

Extension Study: vibegron 100 mg + tolterodine ER 4 mg

Experimental group

Description:

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.

Treatment:

Drug: Vibegron

Drug: Tolterodine ER