Trial Outcomes & Findings for A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002) (NCT NCT03615183)

Results Overview

Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Baseline and 168 hours postdose

Results posted on

2020-09-28

Participant Flow

Anti-retroviral therapy (ART)-naïve, participants with human immunodeficiency type 1 virus (HIV-1) infection were enrolled in this study.

Participant milestones

Participant milestones
Measure	Panel A: MK-8527 10 mg Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Overall Study STARTED	6	6	5
Overall Study COMPLETED	6	6	5
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast	Panel D: ≤50 mg MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.	Panel E: ≤50 mg MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.	Total n=17 Participants Total of all reporting groups
Age, Continuous	28.8 Years STANDARD_DEVIATION 2.3 • n=93 Participants	33.3 Years STANDARD_DEVIATION 9.0 • n=4 Participants	31.2 Years STANDARD_DEVIATION 5.6 • n=27 Participants	—	—	31.1 Years STANDARD_DEVIATION 6.2 • n=10 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	—	—	3 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	—	—	14 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	6 Participants n=4 Participants	5 Participants n=27 Participants	—	—	17 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	6 Participants n=4 Participants	5 Participants n=27 Participants	—	—	17 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	—	—	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline and 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Change From Baseline in Plasma HIV-1 RNA	-1.39 log10 copies/mL Interval -1.78 to -0.99	-1.66 log10 copies/mL Interval -2.06 to -1.27	-0.95 log10 copies/mL Interval -1.38 to -0.52

PRIMARY outcome

Timeframe: Up to 28 days

Population: Participants who received at least one dose of the investigational drug.

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Percentage of Participants Who Report 1 or More Adverse Events (AEs)	0 Percentage of participants	33.3 Percentage of participants	0 Percentage of participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: Participants who received at least one dose of the investigational drug.

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Percentage of Participants Who Were Discontinued From the Study Due to an AE	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527-triphosphate (MK-8527-TP) in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% confidence intervals (CI) for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC)	178 hr*pmol/10^6 cells Interval 140.0 to 226.0	64.1 hr*pmol/10^6 cells Interval 50.5 to 81.3	29.1 hr*pmol/10^6 cells Interval 22.4 to 37.7

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-last of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC	235 hr*pmol/10^6 cells Interval 182.0 to 302.0	108 hr*pmol/10^6 cells Interval 84.0 to 139.0	49.5 hr*pmol/10^6 cells Interval 37.5 to 65.3

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-Inf of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC	265 hr*pmol/10^6 cells Interval 206.0 to 342.0	146 hr*pmol/10^6 cells Interval 113.0 to 188.0	55.0 hr*pmol/10^6 cells Interval 41.6 to 72.8

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Cmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Maximum Concentration (Cmax) of MK-8527-TP in PBMC	1.81 pmol/10^6 cells Interval 1.4 to 2.35	0.644 pmol/10^6 cells Interval 0.497 to 0.834	0.265 pmol/10^6 cells Interval 0.2 to 0.352

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Tmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Time to Cmax (Tmax) of MK-8527-TP in PBMC	18.00 Hours Interval 12.0 to 24.0	24.00 Hours Interval 12.0 to 24.0	24.00 Hours Interval 12.0 to 96.63

SECONDARY outcome

Timeframe: 168 hours postdose for each panel

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Concentration at 168 Hours (C168) of MK-8527-TP in PBMC	0.509 pmol/10^6 cells Interval 0.371 to 0.698	0.334 pmol/10^6 cells Interval 0.244 to 0.458	0.0978 pmol/10^6 cells Interval 0.0692 to 0.138

SECONDARY outcome

Timeframe: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to approximately 28 days postdose to determine the t1/2 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC	117.84 Hours Geometric Coefficient of Variation 35.00	188.66 Hours Geometric Coefficient of Variation 122.5	210.93 Hours Geometric Coefficient of Variation 14.62

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. The 1 mg MK-8527 arm had insufficient data for one participant. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=4 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma	0.926 hr*μmol/L Interval 0.719 to 1.19	0.152 hr*μmol/L Interval 0.118 to 0.196	0.0189 hr*μmol/L Interval 0.0138 to 0.0258

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-last of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma	0.880 hr*μmol/L Interval 0.669 to 1.16	0.121 hr*μmol/L Interval 0.0919 to 0.159	0.0151 hr*μmol/L Interval 0.0112 to 0.0204

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. The 1 mg MK-8527 arm had insufficient data for four participants. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-inf of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=1 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma	1.10 hr*μmol/L Interval 0.794 to 1.53	0.196 hr*μmol/L Interval 0.141 to 0.272	NA hr*μmol/L NA was due to insufficient participants

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the Cmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Maximum Concentration (Cmax) of MK-8527 in Plasma	0.177 μmol/L Interval 0.114 to 0.276	0.0371 μmol/L Interval 0.0238 to 0.0577	0.0162 μmol/L Interval 0.00998 to 0.0264

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the Tmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Time to Cmax (Tmax) of MK-8527 in Plasma	0.50 Hours Interval 0.5 to 1.0	0.50 Hours Interval 0.5 to 1.0	0.50 Hours Interval 0.5 to 0.5

SECONDARY outcome

Timeframe: 168 hours postdose

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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Concentration at 168 Hours (C168) of MK-8527 in Plasma	NA μmol/L Results were below the lower limit of quantitation.	NA μmol/L Results were below the lower limit of quantitation.	NA μmol/L Results were below the lower limit of quantitation.

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose

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. The 1 mg MK-8527 arm had insufficient data for four participants. Participants from Panels D and E were not analyzed because they were not enrolled in the study.

Blood samples were taken at Predose, up to 168 hours postdose to determine the t1/2 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.

Outcome measures

Outcome measures
Measure	Panel A: MK-8527 10 mg n=6 Participants Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 Participants Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=1 Participants Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma	40.31 Hours Geometric Coefficient of Variation 60.27	12.36 Hours Geometric Coefficient of Variation 78.23	NA Hours Geometric Coefficient of Variation NA NA was due to insufficient participants

Adverse Events

Panel A: MK-8527 10 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Panel B: MK-8527 3 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Panel C: MK-8527 1 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Panel A: MK-8527 10 mg n=6 participants at risk Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast	Panel B: MK-8527 3 mg n=6 participants at risk Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast	Panel C: MK-8527 1 mg n=5 participants at risk Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast
Infections and infestations Pharyngitis	0.00% 0/6 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	16.7% 1/6 • Number of events 1 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	0.00% 0/5 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.
Nervous system disorders Dizziness	0.00% 0/6 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	16.7% 1/6 • Number of events 1 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	0.00% 0/5 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.
Psychiatric disorders Insomnia	0.00% 0/6 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	16.7% 1/6 • Number of events 1 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.	0.00% 0/5 • Up to 28 days Participants who received at least one dose of the investigational drug. Panels D and E were not conducted as the scientific study objectives were met in the conducted panels.

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
Publication restrictions are in place