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)

Merck Sharp & Dohme LLC242 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

242

Conditions

HIV-1 Infection

Interventions

IslatravirDRUG

Islatravir 30 mg capsules taken by mouth.

PlaceboDRUG

Placebo capsules taken by mouth.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (9)

Research Centers of America, LLC ( Site 0007)

Hollywood, Florida, United States

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

Baltimore, Maryland, United States

Celerion, Inc. ( Site 0006)

Lincoln, Nebraska, United States

Outcomes

Primary Outcomes

Number of Participants With ≥1 Adverse Event (AE) Through Week 36

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.

Time frame: Up to 36 weeks

Number of Participants Discontinuing From Study Therapy Due to 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.

Time frame: Up to 20 weeks

Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE

A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.

Time frame: Up to 20 weeks

Number of Participants With ≥1 Drug-related AE Through Week 36

A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.

Time frame: Up to 36 weeks

Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36

An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.

Time frame: Up to 36 weeks

Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').

Data from ClinicalTrials.gov

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Secondary Outcomes

Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL

The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

Time frame: Day 1 and Day 140: predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.

Maximum Plasma Concentration (Cmax) of ISL

The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

Time frame: Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.

Trough Plasma Concentration (Ctrough) of ISL

The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

Time frame: Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose.

Apparent Plasma Terminal Half-life (t1/2) of ISL

The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

Number of Participants With ≥1 AE Through Week 24

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.

Time frame: Up to 24 weeks

Number of Participants With ≥1 Drug-related AE Through Week 24

A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.

Time frame: Up to 24 weeks

Number of Participants With ≥1 SAE Through Week 24

Time frame: Up to 24 weeks

Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24

Time frame: Up to 24 weeks

Number of Participants With ≥1 Drug-related SAE Through Week 24

An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.

Time frame: Up to 24 weeks

Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24

A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).

Time frame: Up to 24 weeks

Number of Participants With an AE Resulting in Death Through Week 24

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.

Time frame: Up to 24 weeks