Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)
Condition: HIV-1 Infection
Intervention: MK-8558
Intervention description: Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and
      anti-retroviral activity of MK-8558 monotherapy in anti-retroviral-naïve human
      immunodeficiency virus type 1 (HIV-1) infected participants. The primary hypothesis is that
      at a dose that exhibits an acceptable safety and tolerability profile, MK-8558 has superior
      anti-retroviral activity compared to historical placebo data.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Other than having HIV infection, is in good health based on medical history, physical
             examination, vital sign (VS) measurements, and laboratory safety tests, at the
             pre-study (screening) visit and/or prior to administration of the study drug

          -  Is documented as being HIV-1 positive

          -  Has a screening plasma HIV-1 ribonucleic acid (RNA) ≥ 2,500 copies/mL within 30 days
             prior to the treatment phase of this study

          -  Has a screening plasma cluster of differentiation 4+ (CD4+) T-cell count of >200/mm^3

          -  Is antiretroviral therapy (ART)-naïve

          -  Is willing to receive no other ART prior to Day 11 post-dose of the trial, unless the
             physician/Investigator believes that there is a strong indication to start ART before
             Day 11

          -  Has a Body Mass Index (BMI) ≤35 kg/m^2

          -  Males must agree to abstinence, or barrier contraception plus partner contraception,
             unless confirmed to be azoospermic due to vasectomy or medical cause, for at least 35
             days after the last dose of MK-8558

          -  Females must not be pregnant or breastfeeding, and must be a woman of nonchildbearing
             potential, or a woman of childbearing potential using highly effective birth control
             with low user dependency or who is abstinent on a long-term and persistent basis
             during the intervention period and at least 35 days after the last dose of study
             medication

        Exclusion Criteria:

          -  Has acute (primary) HIV-1 infection

          -  Has a history of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic (with the exception of Gilbert's disease), immunological
             (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological
             (including stroke and chronic seizures) abnormalities or diseases

          -  Is mentally or legally incapacitated or has a history of a clinically significant
             psychiatric disorder (with the exception of situational depression) of the last 5
             years

          -  Has a history of cancer unless disease is adequately treated and deemed "cured"

          -  Has an estimated creatinine clearance (CrCl) ≤ 90 mL/min

          -  Has a history of significant multiple and/or severe allergies, or has had an
             anaphylactic reaction or significant intolerability to prescription or
             non-prescription drugs or food, or has hereditary galactose intolerance, lactase
             deficiency, or glucose-galactose malabsorption

          -  Is positive for hepatitis B surface antigen

          -  Has a history of chronic hepatitis C unless there has been documented cure

          -  Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
             weeks prior to the pre-study (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 administration of the initial dose of study drug,
             throughout the study, until the post-study visit. There may be certain medications
             that are permitted

          -  Has participated in another investigational study within 4 weeks (or 5 half-lives,
             whichever is greater) prior to the pre-study (screening) visit. The window will be
             derived from the date of the last visit in the previous study

          -  Is under the age of legal consent or not capable of giving consent

          -  Has been committed to an institution by way of official or judicial order

          -  Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to
             restrict smoking to ≤10 cigarettes per day

          -  Consumes more than 3 glasses of alcoholic beverages (1 glass is approximately
             equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits
             [29.5 mL/1 ounce]) per day. Participants who consume 4 glasses of alcoholic beverages
             per day may be enrolled at the discretion of the investigator

          -  Consumes excessive amounts, defined as more than 6 servings (1 serving is
             approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks,
             or other caffeinated beverages per day

          -  Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose;
             rechecks are allowed