Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)

NCT ID: NCT03859739

Last Updated: 2021-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2020-05-29

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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panel A. MK-8558 400 mg

Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.

Group Type: EXPERIMENTAL

MK-8558

Intervention Type: DRUG

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Panel B. MK-8558 at dose level 2

Single oral dose of MK-8558 administered at dose level 2 following a 10-hour fast. Dose level 2 shall not exceed 900 mg. Per protocol, dose will be selected following review of data from panel A.

Group Type: EXPERIMENTAL

MK-8558

Intervention Type: DRUG

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Panel C. MK-8558 at dose level 3

Single oral dose of MK-8558 administered at dose level 3 following a 10-hour fast. Dose level 3 shall not exceed 1600 mg. Per protocol, dose will be selected following review of data from panel B.

Group Type: EXPERIMENTAL

MK-8558

Intervention Type: DRUG

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Panel D. MK-8558 at dose level 4

Single oral dose of MK-8558 administered at dose level 4 following a low-fat breakfast. Dose level 4 shall not exceed 1600 mg. Per protocol, Panel D is optional pending results of Panels A-C, and dose will be selected following review of data from panel C.

Group Type: EXPERIMENTAL

MK-8558

Intervention Type: DRUG

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Interventions

MK-8558

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Charite Research Organisation GmbH ( Site 0001)

Berlin, , Germany

Matei Bals Infectious Diseases Institute ( Site 0002)

Bucharest, București, Romania

Countries

Germany; Romania

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-8558-002

Identifier Type: OTHER

Identifier Source: secondary_id

8558-002

Identifier Type: -

Identifier Source: org_study_id