Trial Outcomes & Findings for A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003) (NCT NCT02217904)

Last Updated: 2019-08-12

Results Overview

Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Baseline and 168 hours (7 days) post-dose

Results posted on

2019-08-12

Participant Flow

Additional panels (F: 0.25 mg islatravir; and G: 30 mg islatravir Extended Observation) were initially planned but were not conducted.

Participant milestones

Participant milestones
Measure	Panel A: 10 mg Islatravir Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir Participants received a single dose of 1 mg islatravir.	Panel E: 0.5 mg Islatravir Participants received a single dose of 0.5 mg islatravir.
Overall Study STARTED	6	6	6	6	6
Overall Study COMPLETED	6	6	6	6	6
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Total n=30 Participants Total of all reporting groups
Age, Continuous	31.5 Years STANDARD_DEVIATION 10.0 • n=5 Participants	42.2 Years STANDARD_DEVIATION 9.8 • n=7 Participants	35.5 Years STANDARD_DEVIATION 9.1 • n=5 Participants	32.7 Years STANDARD_DEVIATION 12.7 • n=4 Participants	35.5 Years STANDARD_DEVIATION 11.3 • n=21 Participants	35.5 Years STANDARD_DEVIATION 10.6 • n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	30 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	27 Participants n=8 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	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 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	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	29 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 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	0 Participants n=21 Participants	0 Participants n=8 Participants
Plasma HIV-1 Ribonucleic Acid (RNA)	4.68 log10 copies/mL STANDARD_DEVIATION 0.39 • n=5 Participants	4.7 log10 copies/mL STANDARD_DEVIATION 0.25 • n=7 Participants	4.17 log10 copies/mL STANDARD_DEVIATION 0.41 • n=5 Participants	4.66 log10 copies/mL STANDARD_DEVIATION 0.2 • n=4 Participants	4.59 log10 copies/mL STANDARD_DEVIATION 0.5 • n=21 Participants	4.56 log10 copies/mL STANDARD_DEVIATION 0.40 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline and 168 hours (7 days) post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had available plasma HIV-1 RNA data at baseline and 168 hours post-dose, and were evaluable for the outcome measure.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose	-1.20 log10 copies/mL Interval -1.46 to -0.95	-1.67 log10 copies/mL Interval -1.92 to -1.42	-1.35 log10 copies/mL Interval -1.6 to -1.1	-1.60 log10 copies/mL Interval -1.85 to -1.34	-1.30 log10 copies/mL Interval -1.55 to -1.05

PRIMARY outcome

Timeframe: Up to 21 days post-dose

Population: All participants who received at least one dose of investigational drug

An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Number of Participants With One or More Adverse Events	6 Participants	5 Participants	5 Participants	6 Participants	5 Participants

SECONDARY outcome

Timeframe: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had AUC0-168hr of triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.

Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine AUC0-168hr.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr)	23.1 hr*pmol/10^6 cells Geometric Coefficient of Variation 83.0	227 hr*pmol/10^6 cells Geometric Coefficient of Variation 33.3	46.9 hr*pmol/10^6 cells Geometric Coefficient of Variation 38.1	926 hr*pmol/10^6 cells Geometric Coefficient of Variation 47.7	35.9 hr*pmol/10^6 cells Geometric Coefficient of Variation 27.6

SECONDARY outcome

Timeframe: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had Cmax of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.

Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine Cmax.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells	0.263 pmol/10^6 cells Geometric Coefficient of Variation 54.5	2.81 pmol/10^6 cells Geometric Coefficient of Variation 49.9	0.495 pmol/10^6 cells Geometric Coefficient of Variation 62.9	8.9 pmol/10^6 cells Geometric Coefficient of Variation 60.3	0.408 pmol/10^6 cells Geometric Coefficient of Variation 49.3

SECONDARY outcome

Timeframe: 168 hours after islatravir administration

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had C168hr of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.

Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine C168hr.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr)	0.116 pmol/10^6 cells Geometric Coefficient of Variation 85.6	0.983 pmol/10^6 cells Geometric Coefficient of Variation 26	0.188 pmol/10^6 cells Geometric Coefficient of Variation 39.2	4.83 pmol/10^6 cells Geometric Coefficient of Variation 85.9	0.164 pmol/10^6 cells Geometric Coefficient of Variation 31.4

SECONDARY outcome

Timeframe: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had Tmax of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.

Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine TMax.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells	12 Hour Interval 4.0 to 24.0	12 Hour Interval 12.0 to 240.0	8 Hour Interval 4.0 to 144.0	24 Hour Interval 4.0 to 96.0	8 Hour Interval 4.0 to 24.0

SECONDARY outcome

Timeframe: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had apparent terminal t1/2 of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.

Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine apparent terminal t1/2.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=5 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells	95.3 Hours Geometric Coefficient of Variation 38.2	128 Hours Geometric Coefficient of Variation 42.2	120 Hours Geometric Coefficient of Variation 14.7	78.5 Hours Geometric Coefficient of Variation 31.4	118 Hours Geometric Coefficient of Variation 16.1

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated.

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma AUC-168hr of islatravir data available, and were evaluable for the outcome measure.

Blood was collected for the determination of AUC0-168hr of islatravir in plasma.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr)	38.3 hr*nM Geometric Coefficient of Variation 25.8	1020 hr*nM Geometric Coefficient of Variation 16.8	143 hr*nM Geometric Coefficient of Variation 39.6	3020 hr*nM Geometric Coefficient of Variation 24.6	88.3 hr*nM Geometric Coefficient of Variation 33.8

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma Cmax of islatravir data available, and were evaluable for the outcome measure.

Blood was collected for the determination of Cmax of islatravir in plasma.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Maximum Plasma Concentration (Cmax) of Islatravir	20.3 nM Geometric Coefficient of Variation 36.4	235 nM Geometric Coefficient of Variation 32.1	43.8 nM Geometric Coefficient of Variation 51.2	678 nM Geometric Coefficient of Variation 29.6	38.8 nM Geometric Coefficient of Variation 31.3

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma Tmax of islatravir data available, and were evaluable for the outcome measure.

Blood was collected for the determination of Tmax of islatravir in plasma.

Outcome measures

Outcome measures
Measure	Panel E: 0.5 mg Islatravir n=6 Participants Participants received a single dose of 0.5 mg islatravir.	Panel A: 10 mg Islatravir n=6 Participants Participants received a single dose of 10 mg islatravir.	Panel B: 2 mg Islatravir n=6 Participants Participants received a single dose of 2 mg islatravir.	Panel C: 30 mg Islatravir n=6 Participants Participants received a single dose of 30 mg islatravir.	Panel D: 1 mg Islatravir n=6 Participants Participants received a single dose of 1 mg islatravir.
Time to Maximum Plasma Concentration (Tmax) of Islatravir	0.5 Hour Interval 0.25 to 0.5	1 Hour Interval 0.5 to 1.0	0.5 Hour Interval 0.5 to 1.0	0.75 Hour Interval 0.5 to 1.0	0.5 Hour Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had apparent terminal t1/2 of islatravir in plasma data available, and were evaluable for the outcome measure.

Blood was collected for the determination of apparent terminal t1/2 of islatravir in plasma.