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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV-1

Treatments: Drug: 0.25 mg islatravir; Drug: 30 mg islatravir; Drug: 0.5 mg islatravir; Drug: 10 mg islatravir; Drug: 1 mg islatravir; Drug: 2 mg islatravir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02217904

2014-002192-28 (EudraCT Number)

8591-003

MK-8591-003 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 7 patient groups

Islatravir 1 mg

Experimental group

Description:

Single oral dose of islatravir 1 mg

Treatment:

Drug: 1 mg islatravir

Islatravir 2 mg

Experimental group

Description:

Single oral dose of islatravir 2 mg

Treatment:

Drug: 2 mg islatravir

Islatravir 10 mg

Experimental group

Description:

Single oral dose of islatravir 10 mg

Treatment:

Drug: 10 mg islatravir

Islatravir 30 mg

Experimental group

Description:

Single oral dose of islatravir 30 mg

Treatment:

Drug: 30 mg islatravir

Islatravir 0.5 mg

Experimental group

Description:

Single oral dose of islatravir 0.5 mg

Treatment:

Drug: 0.5 mg islatravir

Islatravir 0.25 mg

Experimental group

Description:

Single oral dose of islatravir 0.25 mg

Treatment:

Drug: 0.25 mg islatravir

Islatravir 30 mg Extended Observation

Experimental group

Description:

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.

Treatment:

Drug: 30 mg islatravir