A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003)

NCT02217904 | Completed Phase 1 Results

• 3 other identifiers: 8591-0032014-002192-28MK-8591-003
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral therapy (ART) activity of islatravir (MK-8591) monotherapy in ART-naive, human immunodeficiency virus-1 (HIV-1) infected participants. The primary hypothesis is that at a safe and tolerable dose of islatravir, the true mean difference in the plasma HIV-1 ribonucleic acid (RNA) reduction from baseline between islatravir and placebo is at least 0.5 log (base10) copies/mL.

Conditions

HIV-1

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose

  Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches.

  Baseline and 168 hours (7 days) post-dose

• Number of Participants With One or More Adverse Events

  An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

  Up to 21 days post-dose

Secondary Outcomes (9)

• Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr)

  4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

• Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells

  4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

• Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr)

  168 hours after islatravir administration

• Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells

  4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

• Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells

  4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

Study Arms (7)

Islatravir 1 mg

EXPERIMENTAL

Single oral dose of islatravir 1 mg

Drug: 1 mg islatravir

Islatravir 2 mg

EXPERIMENTAL

Single oral dose of islatravir 2 mg

Drug: 2 mg islatravir

Islatravir 10 mg

EXPERIMENTAL

Single oral dose of islatravir 10 mg

Drug: 10 mg islatravir

Islatravir 30 mg

EXPERIMENTAL

Single oral dose of islatravir 30 mg

Drug: 30 mg islatravir

Islatravir 0.5 mg

EXPERIMENTAL

Single oral dose of islatravir 0.5 mg

Drug: 0.5 mg islatravir

Islatravir 0.25 mg

EXPERIMENTAL

Single oral dose of islatravir 0.25 mg

Drug: 0.25 mg islatravir

Islatravir 30 mg Extended Observation

EXPERIMENTAL

Single oral dose of 30 mg islatravir administered following \>8 hour fast. Participants will be closely monitored for viral load for up to approximately 21 days prior to starting standard of care ART.

Drug: 30 mg islatravir

Interventions

1 mg islatravir DRUG

Single oral dose of 1 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 1 mg

2 mg islatravir DRUG

Single oral dose of 2 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 2 mg

10 mg islatravir DRUG

Single oral dose of 10 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 10 mg

30 mg islatravir DRUG

Single oral dose of 30 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 30 mg; Islatravir 30 mg Extended Observation

0.5 mg islatravir DRUG

Single oral dose of 0.5 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 0.5 mg

0.25 mg islatravir DRUG

Single oral dose of 0.25 mg islatravir administered following ≥8 hour fast

Also known as: MK-8591

Islatravir 0.25 mg

Eligibility Criteria

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

You may qualify if:

• Non-pregnant, non-breast feeding, postmenopausal or surgically sterile female
• Female with reproductive potential agrees to use (or have male partner use) two acceptable methods of birth control
• Male agrees to use acceptable method of contraception during study and for 90 days after last dose of trial drug
• Has stable baseline health, other than HIV infection
• Has no significantly abnormal electrocardiogram
• Is HIV-1 positive
• Is ART naive
• Has not received any investigational agent or marketed ART within 30 days of trial drug administration
• Is diagnosed with HIV-1 infection \>= 3 months prior to screening
• Is willing to receive no other ART during treatment phase of study
• Has no evidence of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs)

You may not qualify if:

• Is mentally or legally institutionalized/incapacitated, or has significant emotional problems, or has a history of clinically significant psychiatric disorder of the last 5 years
• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, major neurological abnormalities or diseases
• Has a history of cancer (malignancy)
• Has a history of significant multiple and/or severe allergies, or had an anaphylactic reaction to drugs or food
• Is positive for hepatitis B surface antigen
• Has a history of chronic Hepatitis C
• Had major surgery or lost 500 mL of blood with 4 weeks prior to screening visit
• Has participated in another investigational trial within 4 weeks prior to dosing visit
• Will use any medications, prescribed drugs, or herbal remedies 4 weeks prior to dosing of trial drug, up to the post-trial visit
• Consumes excessive amounts of alcohol, caffeinated beverages, or tobacco products
• Uses illicit drugs or has a history of drug abuse within the prior 2 years

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Schurmann D, Rudd DJ, Zhang S, De Lepeleire I, Robberechts M, Friedman E, Keicher C, Huser A, Hofmann J, Grobler JA, Stoch SA, Iwamoto M, Matthews RP. Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Lancet HIV. 2020 Mar;7(3):e164-e172. doi: 10.1016/S2352-3018(19)30372-8. Epub 2020 Jan 3.

  PMID: 31911147 DERIVED

MeSH Terms

Interventions

islatravir

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2014
• First Posted: August 15, 2014
• Study Start: September 17, 2015
• Primary Completion: May 11, 2017
• Study Completion: May 11, 2017
• Last Updated: August 12, 2019
• Results First Posted: December 3, 2018

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share