Clinical trial NCT03859739: Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)
Official title: A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-03-01
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration
timeFrame: Baseline and 168 hours post-dose
measure: Number of Participants Experiencing ≥1 Adverse Event (AE)
timeFrame: Up to 35 days post-dose
measure: Number of Participants Who Discontinued From the Study Due to an AE
timeFrame: Up to 35 days post-dose
Secondary outcomes:
measure: Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose
measure: Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Maximum Observed Concentration (Cmax) for MK-8558 in Plasma
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma
timeFrame: 168 hours post-dose
measure: Apparent Clearance (CL/F) for MK-8558
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) for MK-8558
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
measure: Terminal Half Life (t1/2) for MK-8558
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH ( Site 0001)
city: Bucharest
country: Romania
facility: Matei Bals Infectious Diseases Institute ( Site 0002)
state: Bucuresti
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: