Single-Dose Study of MK-4250 Monotherapy in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-4250-002)
Condition: HIV-1 Infection
Intervention: MK-4250
Intervention description: MK-4250 tablets for oral administration
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral
      activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected
      participants. The primary hypothesis of the study is that at a dose that is sufficiently safe
      and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a
      historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid
      (RNA) (log10 copies/mL) at 168 hours postdose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or non-pregnant and non-breast feeding female

          -  If female with reproductive potential: must demonstrate a serum β-human chorionic
             gonadotropin (β -hCG) level consistent with the nongravid state and agree to use a
             highly effective method of birth control until 30 days after the dose of trial drug

          -  If postmenopausal female: without menses for at least 1 year and has a documented
             follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial
             (screening), AND/OR status post hysterectomy or oophorectomy

          -  Documented HIV-1 positive as determined by a positive Enzyme-linked Immunosorbent
             Assay (ELISA) or Quantitative Polymerase Chain Reaction (QT-PCR) with confirmation
             (e.g., Western Blot).

          -  No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R)
             affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs)

          -  Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV
             infection

          -  Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3

          -  Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment
             phase of this study

          -  Anti-retroviral therapy (ART)-naïve, which is defined as having never received any
             antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral
             agent which is not an InSTI and no exposure to such an investigational antiretroviral
             agent within 60 days prior to screening OR ≤60 consecutive days of combination ART
             which does not include an InSTI and no exposure to such ART within 60 days prior to
             screening

          -  Never received any InSTI

          -  Willing to receive no other ART for the duration of the treatment phase of this study

          -  Body Mass Index (BMI) ≤35 kg/m^2

          -  Other than HIV infection, have baseline health judged to be stable

        Exclusion Criteria:

          -  Mentally or legally institutionalized / incapacitated, or significant emotional
             problems at the time of pretrial (screening) visit or expected during the conduct of
             the trial or has a history of clinically significant psychiatric disorder within the
             last 5 years

          -  History of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic, immunological (outside of HIV-1 infection), renal,
             respiratory, genitourinary or major neurological abnormalities or diseases

          -  History of cancer (malignancy). Exceptions: (1) adequately treated non-melanomatous
             skin carcinoma or carcinoma in situ of the cervix; (2) other malignancies which have
             been successfully treated ≥10 years prior to the pretrial (screening) visit with no
             evidence of recurrence; or, (3) deemed highly unlikely to sustain a recurrence for the
             duration of the trial

          -  History of significant multiple and/or severe allergies (e.g., food, drug, latex
             allergy); anaphylactic reaction or significant intolerability (i.e., systemic allergic
             reaction) to prescription or non-prescription drugs or food; or hereditary galactose
             intolerance, lactose deficiency, or glucose-galactose malabsorption.

          -  Positive for hepatitis B surface antigen

          -  History of chronic hepatitis C (HCV) infection. Participants with a documented cure
             and/or a positive serologic test for HCV with a negative HCV viral load may be
             included

          -  Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks
             prior to the pretrial (screening) visit

          -  Participated in another investigational trial within 4 weeks prior to the Day 1 dosing
             visit. The 4 week window will be derived from the date of the last trial medication
             and / or blood collection in a previous trial and/or an adverse event related to trial
             drug to the Day 1 dosing visit of the current trial

          -  Unable to refrain from or anticipates the use of any medication, including
             prescription and non-prescription drugs or herbal remedies beginning approximately 2
             weeks prior to administration of the initial dose of trial drug, throughout the trial,
             until the post-trial visit

          -  Consumes greater 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

          -  Consumes excessive amounts, defined as greater 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

          -  Excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict
             smoking to ≤10 cigarettes per day

          -  Cardiac QTc interval ≥470 msec (for males) or ≥480 msec (for females)

          -  Positive urine drug screen (except for cannabis) at screening and/or predose; rechecks
             are allowed

          -  Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
             child) who is investigational site or Sponsor staff directly involved with this trial.