The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)
Condition: Hepatic Insufficiency
MeSH terms: Hepatic Insufficiency; Liver Failure
Intervention: Elbasvir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the pharmacokinetics (PK) profile of elbasvir
      (MK-8742) after a single dose to participants with mild, moderate, or severe hepatic
      insufficiency compared with healthy controls.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body mass index (BMI) 19 - 40 kg/m^2, inclusive

          -  In good health based on medical history, physical examination, vital signs, and
             laboratory safety tests

          -  No clinically significant abnormality on electrocardiogram (ECG)

          -  For participants with hepatic insufficiency only, diagnosis of chronic (> 6 months),
             stable (no acute episodes of illness within the previous 2 months due to deterioration
             in hepatic function) hepatic insufficiency with features of cirrhosis due to any cause

          -  For participants with hepatic insufficiency only, score on the Child-Pugh scale must
             range from 5 to 6 for mild hepatic insufficiency, from 7 to 9 for moderate hepatic
             insufficiency, and from 10 to 15 for severe hepatic insufficiency

          -  Females of childbearing potential must be either be sexually inactive (abstinent) for
             14 days before study drug administration and throughout the study or be using an
             acceptable method of birth control

          -  Females of non-childbearing potential must have undergone sterilization procedures at
             least 6 months before Study Day 1

          -  Non-vasectomized males must agree to use a condom with spermicide or abstain from
             sexual intercourse during the study and for 3 months after study drug administration

          -  Ability to swallow multiple capsules

        Exclusion Criteria:

          -  Previously enrolled in this study

          -  Mentally or legally incapacitated, significant emotional problems at the time of
             screening or expected during the conduct of the study, or a history of a clinically
             significant psychiatric disorder over the last 5 years

          -  History or presence of significant cardiovascular, pulmonary, renal, hematologic,
             gastrointestinal, endocrine, immunologic, dermatologic, neurological disease

          -  History of any illness that might confound the results of the study or pose an
             additional risk to the participant by participating in the study

          -  For participants with hepatic insufficiency only, estimated creatinine clearance
             (CrCl) ≤30 mL/min based on the Cockcroft-Gault equation at screening

          -  History or presence of drug abuse within the past 2 years

          -  For healthy participants only, history of alcoholism within the past 2 years

          -  Females who are pregnant or lactating

          -  Positive results for the urine drug screen at screening or check-in

          -  Positive results at screening or history of human immunodeficiency virus (HIV) or
             untreated hepatitis C virus (HCV); HCV ribonucleic acid (RNA)-negative participants
             documented to be cured following anti-HCV treatment are eligible

          -  For healthy participants only, positive results at screening for hepatitis B surface
             antigen (HBsAg)

          -  Use of any drugs or substances known to be strong inhibitors of cytochrome P450 3A4
             (CYP3A4) enzymes and/or P-glycoprotein (P-gp) or any inhibitors of organic anion
             transporting peptide 1B (OATP1B) within 14 days or 5-times the half-life of the
             product (for healthy participants) or which cannot be discontinued at least 14 days or
             5 times the half-life of the product (for hepatic insufficiency participants) before
             study drug administration and throughout the study

          -  Use of any drugs or substances known to be strong inducers of CYP3A4 enzymes and/or
             P-gp, including St-John's Wort or rifampin, within 28 days or 5 times the half-life of
             the product before study drug administration

          -  Currently use of any medication or substance which cannot be discontinued or
             maintained at a steady dose and regimen at least 14 days before study drug
             administration and throughout the study

          -  For healthy participants only, on a special diet within 28 days before study drug
             administration

          -  Blood donation >500 mL or significant blood loss within 56 days before study drug
             administration

          -  Plasma donation within 7 days before study drug administration

          -  Participation in another clinical study within 28 days before study drug
             administration