A Study of the Pharmacokinetics of Uprifosbuvir (MK-3682) and Ruzasvir (MK-8408) in Participants With Moderate and Severe Hepatic Insufficiency (MK-3682-029)
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatic Insufficiency; Liver Failure
Intervention: Uprifosbuvir; Ruzasvir
Intervention description: A single dose of uprifosbuvir 450 mg (given as three 150-mg tablets) taken by mouth.; A single dose of ruzasvir 60 mg (given as six 10-mg capsules) taken by mouth.
Intervention MeSH terms: Ruzasvir; Uprifosbuvir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility 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;