A Study of the Pharmacokinetics of Uprifosbuvir (MK-3682) and Ruzasvir (MK-8408) in Participants With Moderate and Severe Hepatic Insufficiency (MK-3682-029)

• Status: Completed
• Trial end date: 2017-01-16
• Target enrollment: 0
• Participant gender: All

Summary

This is a non-randomized, open-label, single-dose study to evaluate the pharmacokinetics (PK) of uprifosbuvir (MK-3682), the M5 and M6 metabolites of uprifosbuvir, and ruzasvir (MK-8408), in participants with moderate hepatic insufficiency (HI), participants with severe HI, and age-matched healthy control participants.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Ruzasvir; Uprifosbuvir

Criteria

Inclusion Criteria:

HI Participants Only:

• Has a diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI features of cirrhosis;

• Part 1 only: Participant's score on the Child-Pugh scale ranges from 7 to 9 (moderate HI) at study start.

• Part 2 only: Participant's score on the Child-Pugh scale ranges from 10 to 15 (severe HI) at study start.

All Participants:

• Body mass index (BMI) ≥19 and ≤ 40 kg/m^2;

• Continuous non-smokers or moderate smokers (of fewer than 20 cigarettes/day or the equivalent). Participants must agree to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of sample collection;

• Health is judged to be stable based on medical history (except for the hepatic impairment condition), physical examination, vital signs, electrocardiogram (ECGs), and laboratory safety tests;

• For female participants of childbearing potential: either sexually inactive for 14 days prior to study start and throughout study or be using an acceptable birth control method;

• Female participants who are sexually inactive, but become sexually active during the course of the study must agree to use a double physical barrier method (e.g., condom and diaphragm) and a chemical barrier (e.g., spermicide) from the time of the start of sexual activity through completion of the study;

• Vasectomized or non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing;

• Male participants must agree not to donate sperm from dosing until 90 days after dosing;

• Able to swallow multiple tablets and capsules.

Exclusion Criteria:

HI Participants Only:

• Presence of moderate or severe renal insufficiency (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m^2 calculated according to the Modification of Diet in Renal Disease [MDRD] study equation);

• Presence of drug abuse within the past 6 months prior to dosing.

Healthy Participants Only:

• Presence of moderate or severe renal insufficiency (eGFR ≤60 mL/min/1.73 m^2 calculated according to the MDRD study equation);

• History or presence of alcoholism or drug abuse within the past 2 years prior to dosing;

All Participants:

• Is mentally or legally incapacitated or has significant emotional problems at the time of study start or expected during the study;

• History or presence of clinically significant medical or psychiatric condition or disease;

• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds;

• Female participants who are pregnant or lactating;

• Positive results at study start for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);

• Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) for the prohibited time period;

• Has taken amiodarone at any time in their life;

• Donation of blood >500 mL or had significant blood loss within 56 days prior to the dose of study drugs;

• Plasma donation within 7 days prior to the dose of study drugs;

• Dosed in another clinical trial within 28 days prior to dosing of study drugs;