Trial Outcomes & Findings for 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 NCT04003103)

NCT ID: NCT04003103

Last Updated: 2025-07-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 242 participants
• Primary outcome timeframe: Up to 36 weeks
• Results posted on: 2025-07-18

Participant Flow

Healthy HIV-uninfected male and female participants were enrolled at 9 study centers in 3 countries.

Participant milestones

Measure	Islatravir 60 mg Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Overall Study STARTED	97	97	48
Overall Study COMPLETED	82	91	45
Overall Study NOT COMPLETED	15	6	3

Reasons for withdrawal

Measure	Islatravir 60 mg Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Overall Study Death	1	0	0
Overall Study Lost to Follow-up	4	3	2
Overall Study Withdrawal by Subject	10	1	1
Overall Study Status not recorded	0	2	0

Baseline Characteristics

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)

Baseline characteristics by cohort

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Total n=242 Participants Total of all reporting groups
Age, Continuous	33.6 Years STANDARD_DEVIATION 9.9 • n=5 Participants	33.2 Years STANDARD_DEVIATION 9.7 • n=7 Participants	30.9 Years STANDARD_DEVIATION 7.9 • n=5 Participants	32.9 Years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	64 Participants n=7 Participants	33 Participants n=5 Participants	163 Participants n=4 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	33 Participants n=7 Participants	15 Participants n=5 Participants	79 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	36 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	88 Participants n=7 Participants	40 Participants n=5 Participants	206 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	37 Participants n=5 Participants	48 Participants n=7 Participants	16 Participants n=5 Participants	101 Participants n=4 Participants
Race (NIH/OMB) White	55 Participants n=5 Participants	44 Participants n=7 Participants	29 Participants n=5 Participants	128 Participants n=4 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Adverse Event (AE) Through Week 36	66 Participants	63 Participants	36 Participants

PRIMARY outcome

Timeframe: Up to 20 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants Discontinuing From Study Therapy Due to AE	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 20 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related AE Through Week 36	9 Participants	14 Participants	12 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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').

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36	5 Participants	4 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related SAE Through Week 36	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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).

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With an AE Resulting in Death Through Week 36	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=93 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=96 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL Day 1	7.88 hr*umol/L Geometric Coefficient of Variation 56.8	16.6 hr*umol/L Geometric Coefficient of Variation 50.5	—
Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL Day 140	21.2 hr*umol/L Geometric Coefficient of Variation 140.3	37.6 hr*umol/L Geometric Coefficient of Variation 136.6	—

SECONDARY outcome

Timeframe: 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.

Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

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

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Maximum Plasma Concentration (Cmax) of ISL Day 1	0.387 µmol/L Geometric Coefficient of Variation 279.9	0.954 µmol/L Geometric Coefficient of Variation 186.2	—
Maximum Plasma Concentration (Cmax) of ISL Day 140	0.376 µmol/L Geometric Coefficient of Variation 597.7	0.792 µmol/L Geometric Coefficient of Variation 349.6	—

SECONDARY outcome

Timeframe: 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.

Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=92 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=95 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Trough Plasma Concentration (Ctrough) of ISL Day 1	0.000556 µmol/L Geometric Coefficient of Variation 36.6	0.00101 µmol/L Geometric Coefficient of Variation 37.0	—
Trough Plasma Concentration (Ctrough) of ISL Day 140	0.000809 µmol/L Geometric Coefficient of Variation 37.0	0.000124 µmol/L Geometric Coefficient of Variation 42.0	—

SECONDARY outcome

Timeframe: 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.

Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

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

Outcome measures

Measure	Islatravir 60 mg n=81 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=92 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Apparent Plasma Terminal Half-life (t1/2) of ISL Day 1	NA Hours Geometric Coefficient of Variation NA Insufficient data available on Day 1.	NA Hours Geometric Coefficient of Variation NA Insufficient data available on Day 1.	—
Apparent Plasma Terminal Half-life (t1/2) of ISL Day 140	175 Hours Geometric Coefficient of Variation 16.2	177 Hours Geometric Coefficient of Variation 19.8	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 AE Through Week 24	58 Participants	60 Participants	32 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related AE Through Week 24	9 Participants	14 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 SAE Through Week 24	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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').

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24	3 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related SAE Through Week 24	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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).

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received ≥1 dose of study therapy are included.

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.

Outcome measures

Measure	Islatravir 60 mg n=97 Participants Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 Participants Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 Participants Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Number of Participants With an AE Resulting in Death Through Week 24	0 Participants	0 Participants	0 Participants

Adverse Events

Islatravir 60 mg

Serious events: 1 serious events

Other events: 24 other events

Deaths: 1 deaths

Islatravir 120 mg

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Islatravir 60 mg n=97 participants at risk Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 participants at risk Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 participants at risk Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Psychiatric disorders Intentional self-injury	1.0% 1/97 • Up to 36 weeks All treated participants are included.	0.00% 0/97 • Up to 36 weeks All treated participants are included.	0.00% 0/48 • Up to 36 weeks All treated participants are included.
Nervous system disorders Loss of consciousness	1.0% 1/97 • Up to 36 weeks All treated participants are included.	0.00% 0/97 • Up to 36 weeks All treated participants are included.	0.00% 0/48 • Up to 36 weeks All treated participants are included.

Other adverse events

Measure	Islatravir 60 mg n=97 participants at risk Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Islatravir 120 mg n=97 participants at risk Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.	Placebo n=48 participants at risk Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68.
Gastrointestinal disorders Abdominal pain	3.1% 3/97 • Number of events 3 • Up to 36 weeks All treated participants are included.	3.1% 3/97 • Number of events 3 • Up to 36 weeks All treated participants are included.	8.3% 4/48 • Number of events 4 • Up to 36 weeks All treated participants are included.
Gastrointestinal disorders Diarrhoea	5.2% 5/97 • Number of events 5 • Up to 36 weeks All treated participants are included.	4.1% 4/97 • Number of events 5 • Up to 36 weeks All treated participants are included.	8.3% 4/48 • Number of events 4 • Up to 36 weeks All treated participants are included.
Gastrointestinal disorders Nausea	5.2% 5/97 • Number of events 6 • Up to 36 weeks All treated participants are included.	7.2% 7/97 • Number of events 7 • Up to 36 weeks All treated participants are included.	4.2% 2/48 • Number of events 2 • Up to 36 weeks All treated participants are included.
Infections and infestations Upper respiratory tract infection	4.1% 4/97 • Number of events 5 • Up to 36 weeks All treated participants are included.	4.1% 4/97 • Number of events 4 • Up to 36 weeks All treated participants are included.	6.2% 3/48 • Number of events 4 • Up to 36 weeks All treated participants are included.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/97 • Up to 36 weeks All treated participants are included.	1.0% 1/97 • Number of events 1 • Up to 36 weeks All treated participants are included.	6.2% 3/48 • Number of events 3 • Up to 36 weeks All treated participants are included.
Investigations Alanine aminotransferase increased	2.1% 2/97 • Number of events 3 • Up to 36 weeks All treated participants are included.	0.00% 0/97 • Up to 36 weeks All treated participants are included.	6.2% 3/48 • Number of events 3 • Up to 36 weeks All treated participants are included.
Investigations Blood pressure increased	1.0% 1/97 • Number of events 2 • Up to 36 weeks All treated participants are included.	5.2% 5/97 • Number of events 5 • Up to 36 weeks All treated participants are included.	0.00% 0/48 • Up to 36 weeks All treated participants are included.
Nervous system disorders Dizziness	2.1% 2/97 • Number of events 2 • Up to 36 weeks All treated participants are included.	0.00% 0/97 • Up to 36 weeks All treated participants are included.	6.2% 3/48 • Number of events 4 • Up to 36 weeks All treated participants are included.
Nervous system disorders Headache	10.3% 10/97 • Number of events 27 • Up to 36 weeks All treated participants are included.	9.3% 9/97 • Number of events 9 • Up to 36 weeks All treated participants are included.	4.2% 2/48 • Number of events 2 • Up to 36 weeks All treated participants are included.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
• Publication restrictions are in place

Restriction type: OTHER