Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)
Condition: Human Immunodeficiency Virus (HIV) Infection
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Islatravir
Intervention description: Two ISL 30 mg capsules taken by mouth.
Intervention MeSH terms: Islatravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is an open-label, single-dose study of the plasma pharmacokinetics (PK), safety, and
      tolerability of islatravir (ISL, MK-8591), and the intracellular PK of ISL triphosphate
      (ISL-TP) in male and female adult participants with moderate hepatic impairment and in
      healthy matched control participants.
    

Eligibility criteria:

        Inclusion Criteria:

        Healthy Control Participants:

          -  Is in good health based on medical history, physical examination, vital sign (VS)
             measurements and electrocardiograms (ECGs) performed prior to randomization

          -  Is in good health based on laboratory safety tests obtained at the screening visit and
             prior to administration of the initial dose of study drug.

          -  Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2

        Hepatic Impairment Participants:

          -  Has a 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 etiology

          -  Has a score on the Child-Pugh scale ranging from 7 to 9 (moderate hepatic
             insufficiency) at screening

          -  With the exception of hepatic impairment, is in generally good health

          -  Has a BMI ≥ 18.5 and ≤ 40 kg/m2

        Healthy and Hepatic Impairment Participants:

          -  Males : uses contraception according to local regulations

          -  Females: is not pregnant or breastfeeding and one of the following applies:

          -  Is not a woman of childbearing potential (WOCBP) OR

          -  Is a WOCBP and uses an acceptable contraceptive method

          -  A WOCBP with negative highly sensitive pregnancy test within 24 hours of study
             intervention

        Exclusion Criteria:

          -  Has a history of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic, immunological, renal, respiratory, genitourinary, or major
             neurological (including stroke and chronic seizures) abnormalities or diseases

          -  Is mentally or legally incapacitated, has significant emotional problems at the time
             of prestudy (screening) visit or expected during the conduct of the study or has a
             history of clinically significant psychiatric disorder of the last 5 years

          -  Has a history of cancer (malignancy)

          -  Has a history of significant multiple and/or severe allergies, or has had an
             anaphylactic reaction or significant intolerability (ie, systemic allergic reaction)
             to prescription or non-prescription drugs or food

          -  Has known hypersensitivity to the active substance or any of the excipients of the
             study drug

          -  Is positive for hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or HIV-2

          -  Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
             weeks prior to the prestudy (screening) visit

          -  Is unable to refrain from or anticipates the use of any medication, including
             prescription and nonprescription drugs or herbal remedies beginning approximately 2
             weeks (or 5 half-lives) prior to study drug administration, throughout the study,
             until the poststudy visit

          -  Has participated in another investigational study within 4 weeks (or 5 half-lives,
             whichever is greater) prior to the prestudy (screening) visit

          -  Has a QTc interval >470 for males or >480 ms for females, has a history of risk
             factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of
             long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking
             concomitant medications that prolong the QT/QTc interval

          -  Is not considered low risk of having HIV infection

          -  Is a smoker or user of electronic cigarettes and/or has used nicotine or
             nicotine-containing products (eg, nicotine patch) within 3 months of screening

          -  Consumes greater than 3 glasses of alcoholic beverages per day

          -  Consumes more than 6 caffeinated beverages per day

          -  Is a regular user of illicit drugs or has a history of drug abuse within 2 years

          -  Presents any concern to the investigator regarding safe study participation

          -  Is unwilling to comply with study restrictions

          -  Is or has an immediate family member who is investigational site or Sponsor staff
             directly involved with this study