NCT04303156

Pharmacokinetics of Islatravir in Participants With Severe Renal Impairment (MK-8591-026)

Completed Phase 1 Results posted Last updated 28 October 2021

What this trial tests

Phase 1 trial testing Islatravir in Human Immunodeficiency Virus (HIV) Infection in 12 participants. Completed in 19 October 2020.

Timeline

18 June 2020

Primary endpoint
19 October 2020

19 October 2020

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	18 June 2020
Primary completion	19 October 2020
Estimated completion	19 October 2020
Sites	2 locations across United States, Germany

Drugs / interventions tested

• Islatravir — full drug profile →

Conditions studied

• Human Immunodeficiency Virus (HIV) Infection — all drugs for Human Immunodeficiency Virus (HIV) Infection →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Human Immunodeficiency Virus (HIV) Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL) Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

Participants were treated with islatravir (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.

Group	Value	95% CI
Severe Renal Impairment	14.4	11.8 – 17.6
Healthy	6.54	4.77 – 8.98

Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	11.0	9.17 – 13.1
Healthy	5.68	4.06 – 7.94

Maximum Concentration (Cmax) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	1.23	1.06 – 1.42
Healthy	1.19	0.699 – 2.04

Time of Maximum Concentration (Tmax) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	1.03	1.00 – 2.00
Healthy	0.75	0.5 – 1.00

Apparent Terminal Half-life (t1/2) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	127	± 7.7
Healthy	72.0	± 15.5

Apparent Clearance (CL/F) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	14.2	11.6 – 17.4
Healthy	31.3	22.8 – 42.9

Apparent Volume of Distribution (Vz/F) of Plasma ISL Primary · Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	2610	2170 – 3140
Healthy	3250	2100 – 5030

AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) Secondary · Pre-dose, 4, 24, 48, 96, 168 hours post-dose

Participants were treated with ISL, and peripheral blood samples were collected from pre-dose up to 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.

Group	Value	95% CI
Severe Renal Impairment	5810	3890 – 8700
Healthy	3920	2830 – 5420

AUC0-last of ISL-TP in PBMC Secondary · Pre-dose, 4, 24, 48, 96, 168 hours post-dose

Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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.

Group	Value	95% CI
Severe Renal Impairment	5200	3670 – 7370
Healthy	3780	2720 – 5230

Cmax of ISL-TP in PBMC Secondary · Pre-dose, 4, 24, 48, 96, 168 hours post-dose

Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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.

Group	Value	95% CI
Severe Renal Impairment	20.3	15.1 – 27.4
Healthy	21.6	13.7 – 34.1

Tmax of ISL-TP in PBMC Secondary · Pre-dose, 4, 24, 48, 96, 168 hours post-dose

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

Group	Value	95% CI
Severe Renal Impairment	36.00	24.00 – 240.12
Healthy	24.00	4.00 – 239.78

Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC Secondary · 24 hours post-dose

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.

Group	Value	95% CI
Severe Renal Impairment	18.4	14.2 – 23.8
Healthy	19.0	12.9 – 28.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) from day of treatment (Day 1) up to day 29. All-cause mortality from day of randomization (Day 1) up to day 29.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Severe Renal Impairment

Serious: 0/6 (0%)

Deaths: 0/6

Healthy

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (1 terms — click to expand)

Reaction	System	Severe Renal Impairment	Healthy
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—

Data from ClinicalTrials.gov NCT04303156 adverse events section.

Sponsor's own description

This study will evaluate the general tolerability and pharmacokinetics (PK) of a single 60 mg dose of MK-8591 (Islatravir) in participants with severe renal insufficiency, compared to participants in good health.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Safety and Pharmacokinetics of Islatravir in Individuals with Severe Renal Insufficiency.
   Matthews RP, Cao Y, Patel M, Weissler VL, et al · · 2022 · cited 12× · PMID 36346229 · DOI 10.1128/aac.00931-22
2. A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.
   Matthews RP, Ankrom W, Handy W, Patel M, et al · · 2025 · cited 1× · PMID 39648614 · DOI 10.1002/cpdd.1492