A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019)
Condition: HIV-1 Infection
MeSH terms: Hepatic Insufficiency; Liver Failure
Intervention: Doravirine
Intervention description: Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study aimed to investigate the influence of hepatic insufficiency on the
      pharmacokinetics (PK) of doravirine (MK-1439). In Part 1, PK of doravirine in participants
      with moderate hepatic insufficiency was compared with that of healthy control subjects
      matched with regard to mean age and weight. If a clinically meaningful increase in exposure
      of doravirine was observed in participants with moderate hepatic insufficiency in Part 1,
      study Part 2 was to evaluate PK of doravirine in participants with mild hepatic
      insufficiency.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body Mass Index (BMI) between 19 and 40 kg/m^2

          -  Continuous non-smoker or moderate smoker of <20 cigarettes or equivalent per day.
             Agrees to consume <=10 cigarettes or equivalent per day from the time of screening
             through the period of sample collection.

          -  In good health and with no clinically significant electrocardiogram abnormality

          -  Hepatic impairment participants: diagnosis of chronic (>6 months), stable hepatic
             insufficiency with features of cirrhosis due to any etiology. Part 1 only: score of 7
             to 9 on the Child-Pugh scale. Part 2: score of 5 to 6 on the Child-Pugh scale.

          -  Females of childbearing potential: sexually inactive for >=14 days before study drug
             administration and throughout the study, or using 2 acceptable methods of barrier
             contraception from screening until 14 days after study drug administration.

        Exclusion Criteria:

          -  Mentally or legally incapacitated or has significant emotional problems at the time of
             screening or expected during the study

          -  History or presence of clinically significant medical or psychiatric condition or
             disease

          -  History or presence of drug abuse within the past 2 years

          -  History or presence of hypersensitivity or idiosyncratic reaction to the study drug or
             related compounds

          -  Female participant who is pregnant or lactating

          -  Positive results for breath alcohol or urine drug screen (unless due to prescription
             drug use and is approved by the investigator) at screening

          -  Positive for HIV at screening

          -  Unable to refrain from or anticipates the use of any drug known to be a significant
             inhibitor or inducer of cytochrome oxidase CYP3A or P-glycoprotein, or any medication
             or substance which cannot be discontinued at least 14 days before study drug
             administration and throughout the study.

          -  Donation of >500 mL of blood or had significant blood loss within 56 days before study
             drug administration

          -  Plasma donation within 7 days before study drug administration

          -  Dosed in another clinical trial within 28 days before study drug administration

          -  Healthy control participants only: positive for hepatitis B surface antigen (HBsAg) or
             hepatitis C virus (HCV) at screening;