Trial Outcomes & Findings for Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030) (NCT NCT04515641)

NCT ID: NCT04515641

Last Updated: 2025-07-17

Results Overview

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
• Results posted on: 2025-07-17

Participant Flow

Male and females with moderate hepatic impairment between the ages of 18 and 75 years old (inclusive), and healthy matched controls were enrolled in this study

Participant milestones

Measure	Participants With Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)

Baseline characteristics by cohort

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.	Total n=12 Participants Total of all reporting groups
Age, Continuous	60.5 Years STANDARD_DEVIATION 9.4 • n=5 Participants	59.5 Years STANDARD_DEVIATION 6.6 • n=7 Participants	60.0 Years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma	5.81 Hours*μmol/Liter Interval 5.08 to 6.64	7.74 Hours*μmol/Liter Interval 5.67 to 10.6

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma	5.25 Hours*μmol/Liter Interval 4.55 to 6.07	6.97 Hours*μmol/Liter Interval 5.04 to 9.63

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Maximum Concentration (Cmax) of ISL in Plasma	0.834 μmol/Liter Interval 0.44 to 1.58	1.28 μmol/Liter Interval 0.822 to 1.98

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Time to Maximum Concentration (Tmax) of ISL in Plasma	1.00 Hours Interval 1.0 to 6.0	1.00 Hours Interval 1.0 to 2.0

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Apparent Terminal Half-Life (t½) of ISL in Plasma	72.9 Hours Geometric Coefficient of Variation 13.6	83.9 Hours Geometric Coefficient of Variation 12.0

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Apparent Total Clearance (CL/F) of ISL in Plasma	35.1 Liters/Hour Geometric Coefficient of Variation 12.9	26.5 Liters/Hour Geometric Coefficient of Variation 30.3

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma	3714 Liters Geometric Coefficient of Variation 18.4	3197 Liters Geometric Coefficient of Variation 38.6

SECONDARY outcome

Timeframe: Up to 28 days

Population: All participants who received at least one dose of treatment.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Percentage of Participants With an Adverse Event (AE)	16.7 Percentage of participants	16.7 Percentage of participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: All participants who received at least one dose of treatment.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Percentage of Participants Who Discontinued From the Study Due to an AE	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC)	19500 hours*μmol/Liter Interval 15200.0 to 25000.0	25700 hours*μmol/Liter Interval 19000.0 to 34700.0

SECONDARY outcome

Timeframe: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
AUC0-last of ISL-TP in PBMC	18600 hours*μmol/Liter Interval 14700.0 to 23500.0	24100 hours*μmol/Liter Interval 17300.0 to 33600.0

SECONDARY outcome

Timeframe: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Cmax of ISL-TP in PBMC	109 μmol/Liter Interval 83.7 to 141.0	113 μmol/Liter Interval 68.0 to 189.0

SECONDARY outcome

Timeframe: 24 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected at 24 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC	103 μmol/Liter Interval 74.7 to 141.0	97.6 μmol/Liter Interval 54.3 to 175.0

SECONDARY outcome

Timeframe: 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected at 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC	39.9 μmol/Liter Interval 30.0 to 53.1	46.4 μmol/Liter Interval 29.6 to 72.6

SECONDARY outcome

Timeframe: 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected at 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC	3.80 μmol/Liter Interval 2.25 to 6.42	5.82 μmol/Liter Interval 4.38 to 7.74

SECONDARY outcome

Timeframe: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Tmax of ISL-TP was expressed as a median.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Tmax of ISL-TP in PBMC	24.00 Hours Interval 4.0 to 48.0	48.00 Hours Interval 24.0 to 96.0

SECONDARY outcome

Timeframe: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.

Participants were treated with ISL, and peripheral blood samples were collected from pre-dose to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
T1/2 of ISL-TP in PBMC	148 Hours Geometric Coefficient of Variation 18.4	169 Hours Geometric Coefficient of Variation 31.9

Adverse Events

Participants With Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Healthy Matched Control Participants

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Participants With Moderate Hepatic Impairment n=6 participants at risk Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form.	Healthy Matched Control Participants n=6 participants at risk Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • Up to 28 days All-cause mortality includes all allocated participants and safety includes all participants who received at least one dose of study treatment.	16.7% 1/6 • Number of events 1 • Up to 28 days All-cause mortality includes all allocated participants and safety includes all participants who received at least one dose of study treatment.

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