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

NCT ID: NCT02217904

Last Updated: 2019-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-17
• Study Completion Date: 2017-05-11

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Islatravir 1 mg

Single oral dose of islatravir 1 mg

Group Type: EXPERIMENTAL

1 mg islatravir

Intervention Type: DRUG

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

Islatravir 2 mg

Single oral dose of islatravir 2 mg

Group Type: EXPERIMENTAL

2 mg islatravir

Intervention Type: DRUG

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

Islatravir 10 mg

Single oral dose of islatravir 10 mg

Group Type: EXPERIMENTAL

10 mg islatravir

Intervention Type: DRUG

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

Islatravir 30 mg

Single oral dose of islatravir 30 mg

Group Type: EXPERIMENTAL

30 mg islatravir

Intervention Type: DRUG

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

Islatravir 0.5 mg

Single oral dose of islatravir 0.5 mg

Group Type: EXPERIMENTAL

0.5 mg islatravir

Intervention Type: DRUG

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

Islatravir 0.25 mg

Single oral dose of islatravir 0.25 mg

Group Type: EXPERIMENTAL

0.25 mg islatravir

Intervention Type: DRUG

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

Islatravir 30 mg Extended Observation

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.

Group Type: EXPERIMENTAL

30 mg islatravir

Intervention Type: DRUG

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

Interventions

1 mg islatravir

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

Intervention Type: DRUG

2 mg islatravir

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

Intervention Type: DRUG

10 mg islatravir

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

Intervention Type: DRUG

30 mg islatravir

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

Intervention Type: DRUG

0.5 mg islatravir

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

Intervention Type: DRUG

0.25 mg islatravir

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

Intervention Type: DRUG

Other Intervention Names

MK-8591; MK-8591; MK-8591; MK-8591; MK-8591; MK-8591

Eligibility Criteria

Inclusion Criteria

• 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
• Have a screening plasma HIV-1 RNA ≥ 10,000 copies/mL within 30 days prior to the treatment phase of this study. For inclusion in Panel Islatravir Extended Observation, participants must also have a screening plasma HIV-1 RNA ≤ 25,000 copies/mL within 30 days prior to the treatment phase.
• 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)

Exclusion Criteria

• 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

• 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

References

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.

Reference Type: DERIVED

PMID: 31911147 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-002192-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8591-003

Identifier Type: OTHER

Identifier Source: secondary_id

8591-003

Identifier Type: -

Identifier Source: org_study_id