Trial Outcomes & Findings for Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002) (NCT NCT03188523)

Results Overview

Plasma samples were collected from participants after a single dose of MK-8504 to assess viral load. The log10 plasma HIV-RNA (copies/mL) measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. Change from baseline to 168 hours post-dose was determined for each treatment group. Results are expressed as change in HIV RNA log10 (copies/mL).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Baseline, 168 hours post-dose

Results posted on

2019-07-15

Participant Flow

Twelve participants infected with Human Immunodeficiency Virus 1 (HIV-1) were enrolled into Panels A and B. Due to an earlier than anticipated achievement of the study primary study objectives, Panels C and D were not conducted and no participants were enrolled in these panels.

Participant milestones

Participant milestones
Measure	MK-8504 100 mg (Panel A) Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) Participants receive a single oral dose of MK-8504 240 mg.
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

Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.	Total n=12 Participants Total of all reporting groups
Age, Continuous	31.7 Years STANDARD_DEVIATION 6.0 • n=5 Participants	35.5 Years STANDARD_DEVIATION 7.0 • n=7 Participants	33.6 Years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 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	1 Participants n=7 Participants	1 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 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
Baseline Plasma HIV-1 Ribonucleic Acid (RNA)	4.31 Log10 copies/mL STANDARD_DEVIATION 0.34 • n=5 Participants	4.60 Log10 copies/mL STANDARD_DEVIATION 0.64 • n=7 Participants	4.45 Log10 copies/mL STANDARD_DEVIATION 0.51 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 168 hours post-dose

Population: All randomized participants

Plasma samples were collected from participants after a single dose of MK-8504 to assess viral load. The log10 plasma HIV-RNA (copies/mL) measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. Change from baseline to 168 hours post-dose was determined for each treatment group. Results are expressed as change in HIV RNA log10 (copies/mL).

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose	-1.06 log10 (copies/mL) Interval -1.49 to -0.62	-0.95 log10 (copies/mL) Interval -1.38 to -0.51

PRIMARY outcome

Timeframe: From Day 1 through Post-Trial Visit (up to 25 days)

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

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants experiencing at least one AE was reported for each arm.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Number of Participants Who Experienced At Least One Adverse Event (AE)	5 Participants	6 Participants

PRIMARY outcome

Timeframe: Day 1

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

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants that discontinued study treatment due to an AE was reported for each arm.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	0 Participants	0 Participants

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma pharmacokinetic (PK) data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma MK-8504. AUC0-last was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to last measurement, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Last Measurable Concentration (AUC0-last)	2.58 μM·hr Geometric Coefficient of Variation 63.4	6.20 μM·hr Geometric Coefficient of Variation 32.1

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma MK-8504. AUC0-inf was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to infinite time, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Infinity (AUC0-inf)	2.59 μM·hr Geometric Coefficient of Variation 63.0	6.25 μM·hr Geometric Coefficient of Variation 32.0

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma MK-8504. Because plasma MK-8504 was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to 168 Hours (AUC0-168hr)	2.61 μM·hr Geometric Coefficient of Variation 62.4	6.26 μM·hr Geometric Coefficient of Variation 32.5

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma MK-8504. Tmax was defined as the time at which maximum concentration of MK-8504 in plasma was observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Time to Maximum Concentration of MK-8504 in Plasma (Tmax)	1.00 Hour (hr) Interval 0.5 to 2.0	0.75 Hour (hr) Interval 0.5 to 1.0

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma MK-8504. Cmax was defined as the maximum concentration of MK-8504 in plasma observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Maximum Concentration of MK-8504 in Plasma (Cmax)	2.72 μM Geometric Coefficient of Variation 81.6	5.32 μM Geometric Coefficient of Variation 22.5

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma MK-8504. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Apparent Terminal Half Life of MK-8504 in Plasma (t½)	3.02 hr Geometric Coefficient of Variation 38.6	6.27 hr Geometric Coefficient of Variation 29.7

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine CL/F of plasma MK-8504. CL/F was defined as the apparent total clearance of the drug from plasma after oral administration, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Apparent Total Clearance of MK-8504 in Plasma (CL/F)	67.7 liters (L)/hr Geometric Coefficient of Variation 63.0	67.4 liters (L)/hr Geometric Coefficient of Variation 32.0

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine Vz/F of plasma MK-8504. Vz/F was defined as the apparent volume of distribution of the drug in plasma during the terminal phase after non-intravenous administration, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8504 in Plasma	295 liters (L) Geometric Coefficient of Variation 55.1	609 liters (L) Geometric Coefficient of Variation 17.8

SECONDARY outcome

Timeframe: Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-168hr of TFP-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-168hr was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to 168 hours, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to 168 Hours (Intracellular AUC0-168hr) In Peripheral Blood Mononuclear Cells (PBMCs)	346 μM·hr Geometric Coefficient of Variation 22.5	885 μM·hr Geometric Coefficient of Variation 17.8

SECONDARY outcome

Timeframe: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-inf of TFV-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-inf was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to infinite time, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to Infinity (Intracellular AUC0-inf) In Peripheral Blood Mononuclear Cells (PBMCs)	433 μM·hr Geometric Coefficient of Variation 22.9	1020 μM·hr Geometric Coefficient of Variation 19.3

SECONDARY outcome

Timeframe: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Tmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Tmax was defined as the time at which maximum intracellular concentration of TFV-DP in PBMCs was observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Time to Maximum Concentration (Intracellular Tmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs)	4.00 hours (hr) Interval 4.0 to 12.0	12.00 hours (hr) Interval 4.0 to 24.0

SECONDARY outcome

Timeframe: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Cmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Cmax was defined as the maximum intracellular concentration of TFV-DP in PBMCs observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Maximum Concentration (Intracellular Cmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs)	5.89 μM Geometric Coefficient of Variation 22.3	15.1 μM Geometric Coefficient of Variation 52.6

SECONDARY outcome

Timeframe: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular t½ of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular t½ was defined as the time required to divide the intracellular concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Apparent Terminal Half Life (Intracellular t½) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs)	72.4 hour (hr) Geometric Coefficient of Variation 21.5	67.5 hour (hr) Geometric Coefficient of Variation 42.1

SECONDARY outcome

Timeframe: 168 hours post-dose

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data.

Blood samples were collected in a fasted state, processed for PBMC samples, and used to determine the intracellular C168hr of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular C168hr was defined as the intracellular concentration of TFV-DP in PBMCs at 168 hours, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Intracellular Concentration of Tenofovir-Diphosphate (TFV-DP) at 168 Hours (Intracellular C168hr) In Peripheral Blood Mononuclear Cells (PBMCs)	0.910 μM Geometric Coefficient of Variation 19.4	1.35 μM Geometric Coefficient of Variation 24.7

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma pharmacokinetic (PK) data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma tenofovir. AUC0-last was defined as the area under the concentration time curve of plasma tenofovir from time 0 to last measurement, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Last Measurable Concentration (AUC0-last)	1.71 μM·hr Geometric Coefficient of Variation 19.5	4.47 μM·hr Geometric Coefficient of Variation 14.2

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma tenofovir. AUC0-inf was defined as the area under the concentration time curve of plasma tenofovir from time 0 to infinite time, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Infinity (AUC0-inf)	2.19 μM·hr Geometric Coefficient of Variation 27.6	6.00 μM·hr Geometric Coefficient of Variation 19.6

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma tenofovir. Because plasma tenofovir was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to 168 Hours (AUC0-168hr)	2.13 μM·hr Geometric Coefficient of Variation 25.7	5.72 μM·hr Geometric Coefficient of Variation 17.3

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma tenofovir. Tmax was defined as the time at which maximum concentration of tenofovir in plasma was observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Time to Maximum Concentration of Tenofovir in Plasma (Tmax)	2.00 Hour (hr) Interval 1.0 to 2.0	2.00 Hour (hr) Interval 2.0 to 2.0

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma tenofovir. Cmax was defined as the maximum concentration of tenofovir in plasma observed, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Maximum Concentration of Tenofovir in Plasma (Cmax)	0.0727 μM Geometric Coefficient of Variation 25	0.156 μM Geometric Coefficient of Variation 22.8

SECONDARY outcome

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

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data.

Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma tenofovir. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504.

Outcome measures

Outcome measures
Measure	MK-8504 100 mg (Panel A) n=6 Participants Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 Participants Participants receive a single oral dose of MK-8504 240 mg.
Apparent Terminal Half Life of Tenofovir in Plasma (t½)	32.3 hr Geometric Coefficient of Variation 23.7	35.3 hr Geometric Coefficient of Variation 29.0

Adverse Events

MK-8504 100 mg (Panel A)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

MK-8504 240 mg (Panel B)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-8504 100 mg (Panel A) n=6 participants at risk Participants receive a single oral dose of MK-8504 100 mg.	MK-8504 240 mg (Panel B) n=6 participants at risk Participants receive a single oral dose of MK-8504 240 mg.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Number of events 2 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Flatulence	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Rectal tenesmus	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
General disorders Catheter site bruise	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
General disorders Fatigue	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
General disorders Influenza like illness	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Infections and infestations Nasopharyngitis	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Infections and infestations Rhinitis	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Infections and infestations Tooth abscess	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Infections and infestations Tooth infection	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 2 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Nervous system disorders Dizziness	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Nervous system disorders Headache	33.3% 2/6 • Number of events 3 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	50.0% 3/6 • Number of events 6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Psychiatric disorders Abnormal dreams	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Psychiatric disorders Depressed mood	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Psychiatric disorders Insomnia	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • From Day 1 through Post-Trial Visit (up to 25 days) All participants that received at least one dose of treatment.