Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016)

NCT ID: NCT04003103

Last Updated: 2025-07-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

242 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-19

Study Completion Date

2022-11-24

Brief Summary

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This study will evaluate the safety, tolerability and pharmacokinetics (PK) of 6 once-monthly doses of oral islatravir (60 mg and 120 mg) compared with placebo in adults at low risk of HIV-1 infection

Detailed Description

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This study is ongoing for collection of safety follow-up of infants born to mothers participating in the study. The present results are based on the Week 68 interim analysis.

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Islatravir 60 mg

60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

Islatravir 30 mg capsules taken by mouth.

Placebo

Intervention Type DRUG

Placebo capsules taken by mouth.

Islatravir 120 mg

120 mg islatravir administered once monthly, orally in capsule form for 24 weeks

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

Islatravir 30 mg capsules taken by mouth.

Placebo

Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules taken by mouth.

Interventions

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Islatravir

Islatravir 30 mg capsules taken by mouth.

Intervention Type DRUG

Placebo

Placebo capsules taken by mouth.

Intervention Type DRUG

Other Intervention Names

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MK-8591

Eligibility Criteria

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Inclusion Criteria

* Is in general good health with acceptable laboratory values at screening
* Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before randomization
* Has low risk of HIV infection, within 12 months prior to screening visit or the rescreening visit (if applicable)
* Use contraceptives consistent with local regulations
* Female is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP)
* A WOCBP is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; or has a negative pregnancy test.

Exclusion Criteria

* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* Has an active diagnosis of hepatitis due to any cause
* Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 30 days prior to Day

1 through the duration of the study.
* Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to Day1 through the duration of the study.
* Has previously been randomized in a study and received islatravir (MK-8591).
* Female is expecting to conceive or donate eggs at any time during the study
* Has QTc interval (using Fridericia correction) \>450 msec (for males) or \>460 msec (for females) or deemed clinically abnormal by the investigator.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Research Centers of America, LLC ( Site 0007)

Hollywood, Florida, United States

Site Status

Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)

Baltimore, Maryland, United States

Site Status

Celerion, Inc. ( Site 0006)

Lincoln, Nebraska, United States

Site Status

Magee Womens Research Institute ( Site 0001)

Pittsburgh, Pennsylvania, United States

Site Status

Hadassah Ein Karem Jerusalem ( Site 0016)

Jerusalem, Jerusalem, Israel

Site Status

Rambam Medical Center ( Site 0017)

Haifa, , Israel

Site Status

JOSHA Research ( Site 0015)

Bloemfontein, Free State, South Africa

Site Status

Clinical HIV Research Unit CHRU ( Site 0014)

Johannesburg, Gauteng, South Africa

Site Status

Emavundleni Vaccine Centre ( Site 0011)

Cape Town, Western Cape, South Africa

Site Status

Countries

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United States Israel South Africa

References

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Hillier SL, Bekker LG, Riddler SA, Hendrix CW, Badal-Faesen S, Macdonald P, Nair G, Lombaard J, Caraco Y, Peer A, Patel M, Vargo R, Homony B, Nedrow K, Evans B, Wickremasingha P, Zhou YP, Teal V, Hwang P, McMullan C, Kaufman KD, Robertson MN, Plank RM. Safety, Tolerability, and Pharmacokinetics of Once-Monthly Oral Islatravir: a Phase 2a Study in Participants at Low Risk for Acquiring HIV-1. J Infect Dis. 2025 May 6:jiaf222. doi: 10.1093/infdis/jiaf222. Online ahead of print.

Reference Type RESULT
PMID: 40327547 (View on PubMed)

Pham M, Wickremasingha P, Vargo R, Patel M, Nedrow K, Homony B, Robertson MN, Plank RM. Exploratory Substudy of a Phase 2 Trial to Evaluate the Pharmacokinetic Effect of Once-Monthly Islatravir on Long-Acting Reversible Contraceptives. J Acquir Immune Defic Syndr. 2025 Apr 22;99(4):374-8. doi: 10.1097/QAI.0000000000003678. Online ahead of print.

Reference Type DERIVED
PMID: 40260892 (View on PubMed)

Devanathan AS, Cottrell ML. Pharmacology of HIV Cure: Site of Action. Clin Pharmacol Ther. 2021 Apr;109(4):841-855. doi: 10.1002/cpt.2187. Epub 2021 Mar 5.

Reference Type DERIVED
PMID: 33540481 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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Merck Protocol Number

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001704-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591-016

Identifier Type: -

Identifier Source: org_study_id

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