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

NCT03859739 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8558-002MK-8558-002
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

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

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration

  Plasma was collected at baseline and at 168 hours post-dose to determine the change from baseline in HIV-1 ribonucleic acid (RNA) concentration. The log10 plasma HIV-RNA was measured and analyzed based on a longitudinal data analysis (LDA) model containing fixed effects for dose level and time.

  Baseline and 168 hours post-dose

• Number of Participants Experiencing ≥1 Adverse Event (AE)

  An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to 35 days post-dose

• Number of Participants Who Discontinued From the Study Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to 35 days post-dose

Secondary Outcomes (9)

• Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose

• Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma

  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

• Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma

  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

• Maximum Observed Concentration (Cmax) for MK-8558 in Plasma

  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

• Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma

  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

Study Arms (4)

Panel A. MK-8558 400 mg

EXPERIMENTAL

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

Drug: MK-8558

Panel B. MK-8558 at dose level 2

EXPERIMENTAL

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.

Drug: MK-8558

Panel C. MK-8558 at dose level 3

EXPERIMENTAL

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.

Drug: MK-8558

Panel D. MK-8558 at dose level 4

EXPERIMENTAL

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.

Drug: MK-8558

Interventions

MK-8558 DRUG

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

Panel A. MK-8558 400 mg; Panel B. MK-8558 at dose level 2; Panel C. MK-8558 at dose level 3; Panel D. MK-8558 at dose level 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Charite Research Organisation GmbH ( Site 0001)

Berlin, 10117, Germany

Location

Matei Bals Infectious Diseases Institute ( Site 0002)

Bucharest, București, 021105, Romania

Location

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 1, 2019
• Study Start: April 26, 2019
• Primary Completion: May 29, 2020
• Study Completion: May 29, 2020
• Last Updated: May 28, 2021
• Results First Posted: May 28, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share

Locations

RO (1); DE (1)