A Single Dose Study of the Pharmacokinetics of Vibegron (MK-4618) in Participants With Renal Insufficiency (MK-4618-014)

An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-4618 in Patients With Renal Insufficiency

This study will investigate the impact of impaired renal function on the plasma pharmacokinetics of vibegron (MK-4618) to guide use of vibegron in clinical trials in participants with overactive bladder and to guide recommendations on potential dosing adjustments for individuals with varying degrees of renal impairment.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Vibegron 100 mg

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria - Renal Impaired Patients

• Body mass index (BMI) ≤40 kg/m^2
• Clinical diagnosis of renal insufficiency
• Stable baseline health

Inclusion Criteria - Healthy Subjects

- Stable baseline health

Exclusion Criteria - Renal Impaired Patients

• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary disease
• History of recent stroke, chronic seizures, or major neurological disorder
• Demonstrated or suspected renal artery stenosis
• Renal transplant or nephrectomy
• History of cancer excepting certain skin or cervical cancers or cancers that were successfully treated 10 or more years prior to screening
• History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Unable to refrain from or anticipates the use of any medication including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of study drug, throughout the study, and until the post study visit
• Unable to avoid taking diuretics within 4 hours prior to dosing and 4 hours post dosing; must be on a stable dose for at least approximately 2 weeks (or 5 half-lives of the compound, whichever is longer)
• Unwilling to refrain from consuming any food or drink/beverage containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats 2 weeks prior to dosing until the post-study visit
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) within 4 weeks prior to administration of study drug
• Plasma donation within 7 days prior to administration of study drug
• Current regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months
• Nursing mother
• Participation in another investigational study within 4 weeks of study enrollment

Exclusion Criteria - Healthy Subjects

• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of stroke, chronic seizures, or major neurological disorder
• History of cancer excepting certain skin or cervical cancers or cancers that were successfully treated 10 or more years prior to screening
• History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Unable to refrain from or anticipates the use of any medication including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the dose of study drug, throughout the study, until the post study visit
• Unwilling to refrain from consuming any food or drink/beverage containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats 2 weeks prior to dosing until the post study visit
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) within 4 weeks prior to administration of study drug
• Plasma donation within 7 days prior to administration of study drug
• Current regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months
• Nursing mother
• Participation in another investigational study within 4 weeks of study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants With Severe Renal Insufficiency; Participants will receive a single oral dose of vibegron 100 mg on Day 1.	Drug: Vibegron 100 mg; Vibegron tablets, orally, on Day 1; Other Names: MK-4618
Experimental: Participants With Moderate Renal Insufficiency; Participants will receive a single oral dose of vibegron 100 mg on Day 1.	Drug: Vibegron 100 mg; Vibegron tablets, orally, on Day 1; Other Names: MK-4618
Experimental: Participants With Mild Renal Insufficiency; Participants will receive a single oral dose of vibegron 100 mg on Day 1.	Drug: Vibegron 100 mg; Vibegron tablets, orally, on Day 1; Other Names: MK-4618
Experimental: Healthy Matched Control Participants; Participants receive a single oral dose of vibegron 100 mg on Day 1.	Drug: Vibegron 100 mg; Vibegron tablets, orally, on Day 1; Other Names: MK-4618

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg	Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine AUC0-∞ after a single oral dose of vibegron 100 mg.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose
Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg	Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine Cmax after a single oral dose of vibegron 100 mg.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose
Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg	Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine CL/F after a single oral dose of vibegron 100 mg.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2012
• Primary Completion (Actual): January 25, 2013
• Study Completion (Actual): January 25, 2013

Study Registration Dates

• First Submitted: June 22, 2012
• First Submitted That Met QC Criteria: June 22, 2012
• First Posted (Estimate): June 26, 2012

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 3, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Renal Insufficiency
• Other Study ID Numbers: 4618-014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf