Trial Outcomes & Findings for A Single Dose Study of MK-8266 (MK-8266-001) (NCT NCT01025791)

Last Updated: 2019-02-20

Results Overview

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days)

Results posted on

2019-02-20

Participant Flow

Participants were recruited at 2 clinical study sites in Germany and in Belgium.

For Panel A, 5 treatment periods were planned in this study. For Panels B and C, only 4 treatment periods were planned.

Participant milestones

Participant milestones
Measure	Panel A, Healthy Male Participants, Sequence 1 MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: placebo/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.	Panel A, Healthy Male Participants, Sequence 2 MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: placebo/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.	Panel A, Healthy Male Participants, Sequence 3 MK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo.	Panel A, Healthy Male Participants, Sequence 4 MK-8266 in Period 1: placebo/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.	Panel B, Healthy Male Participants, Sequence 1 MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: placebo/ Period 4: 0.4 mg fed/ Period 5: na.	Panel B, Healthy Male Participants, Sequence 2 MK-8266 in Period 1: 0.4 mg/ Period 2: placebo/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na.	Panel B, Healthy Male Participants, Sequence 3 MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na.	Panel B, Healthy Male Participants, Sequence 4 MK-8266 in Period 1: placebo/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na.	Panel C, Mild/Moderate Hypertension, Sequence 1 Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na	Panel C, Mild/Moderate Hypertension, Sequence 2 Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na	Panel C, Mild/Moderate Hypertension, Sequence 3 Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2 placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na	Panel C, Mild/Moderate Hypertension, Sequence 4 Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na	Panel C, Mild/Moderate Hypertension, Sequence 5 Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na	Panel C, Mild/Moderate Hypertension, Sequence 6 Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: placebo/ Period 5: na
Period 1 STARTED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 1 COMPLETED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 1 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 2 STARTED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 2 COMPLETED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 2 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 3 STARTED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 3 COMPLETED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 3 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 4 STARTED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 4 COMPLETED	2	2	2	2	2	2	2	2	2	1	2	1	2	1
Period 4 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 5 STARTED	2	2	2	2	0	0	0	0	0	0	0	0	0	0
Period 5 COMPLETED	2	2	2	2	0	0	0	0	0	0	0	0	0	0
Period 5 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Single Dose Study of MK-8266 (MK-8266-001)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel A MK-8266 (Healthy Males) n=8 Participants MK-8266 single dose or placebo matching MK-8266 in healthy male participants in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.	Panel B MK-8266 (Healthy Males) n=8 Participants MK-8266 single dose or placebo matching MK-8266 in healthy male participants in Periods 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na.	Panel C MK-8266 (Mild/Mod. Hypertension) n=9 Participants MK-8266 single dose or placebo matching MK-8266 (Mild/Mod. Hypertension) in Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na	Total n=25 Participants Total of all reporting groups
Age, Continuous	34.3 Years STANDARD_DEVIATION 8.1 • n=5 Participants	27.3 Years STANDARD_DEVIATION 5.4 • n=7 Participants	47.3 Years STANDARD_DEVIATION 3.9 • n=5 Participants	36.7 Years STANDARD_DEVIATION 10.4 • n=4 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
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days)

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

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) n=6 Participants MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=6 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) n=6 Participants MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) n=6 Participants MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=23 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
Number of Participants Who Experienced One or More Adverse Events	3 Participants	1 Participants	4 Participants	3 Participants	2 Participants	3 Participants	4 Participants	6 Participants	3 Participants	2 Participants	3 Participants	5 Participants	2 Participants	10 Participants	—

PRIMARY outcome

Timeframe: Up to 43 days

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

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) n=6 Participants MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=6 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) n=6 Participants MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) n=6 Participants MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=23 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
Number of Participants Who Discontinued Study Drug Due to an AE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Predose, 1.5, 3, 12, and 24 hours postdose

Population: All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment. Panel B MK-8266 0.4 mg fasted and Panel B MK-8266 0.4 mg fed were combined in the analysis. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis.

Central ascending aortic blood pressure augmentation index (AIx) is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. AIx can be measured non-invasively by radial tonometry using aplanation tonometry of radial artery with the SphygmoCor Pulse Wave Analysis System Guide (SphygmoCor system). AIx was performed at prestudy to ensure an adequate waveform can be obtained. At each time point, a minimum of 2 AIx were completed in an attempt to obtain 2 acceptable quality assessments. A time weighted average was calculated. AIx was adjusted for heart rate. A decrease in the AIx of ≥5 percentage is considered clinically meaningful. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. The 12-hour measurement was not collected (per protocol) in all periods of Panels A and B.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) n=10 Participants MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=12 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=6 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) n=5 Participants MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n=8 Participants MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) n=6 Participants MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo n=12 Participants Placebo to MK-8266
Aortic Augmentation Index - Time-Weighted Average 0-24 Hours	-5.70 Percentage of central pulse pressure Standard Deviation 7.57	-1.73 Percentage of central pulse pressure Standard Deviation 7.36	-13.1 Percentage of central pulse pressure Standard Deviation 8.71	-14.1 Percentage of central pulse pressure Standard Deviation 7.49	-16.7 Percentage of central pulse pressure Standard Deviation 5.21	-15.3 Percentage of central pulse pressure Standard Deviation 2.68	8.43 Percentage of central pulse pressure Standard Deviation 4.98	11.29 Percentage of central pulse pressure Standard Deviation 6.60	7.78 Percentage of central pulse pressure Standard Deviation 11.10	-8.79 Percentage of central pulse pressure Standard Deviation 9.66	-2.96 Percentage of central pulse pressure Standard Deviation 9.15	-1.73 Percentage of central pulse pressure Standard Deviation 4.49	-7.42 Percentage of central pulse pressure Standard Deviation 3.85	8.74 Percentage of central pulse pressure Standard Deviation 3.90	17.74 Percentage of central pulse pressure Standard Deviation 6.75

PRIMARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Population: AUC\[0-inf\] was not estimated at MK-8266 doses \<1.0 mg and for the first 2 doses in Panel C due to the lack of measureable concentrations, and for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis.

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC\[0-inf\] is a measure of the mean concentration levels of drug in the plasma after the dose. AUC\[0-inf\] was not collected, analyzed or summarized for participants receiving placebo.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=5 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	441 mg/mL*hr Standard Deviation 105	—	216 mg/mL*hr Standard Deviation 55.95	350 mg/mL*hr Standard Deviation 49.5	—	—	—	528 mg/mL*hr Standard Deviation 151	623 mg/mL*hr Standard Deviation 350	—	—	—	264 mg/mL*hr Standard Deviation 64.4	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Population: All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model. Cmax was not estimated for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis.

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. For Panel A 1.0/0.8 mg MK-8266, the second dose was not well characterized due to limited sampling. Observed exposure likely underestimates the true exposure. Cmax was not collected, analyzed or summarized for participants receiving placebo.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) n=6 Participants MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=5 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) n=6 Participants MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) n=6 Participants MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax)	20.5 nM Standard Deviation 2.58	7.46 nM Standard Deviation 1.41	19.5 nM Standard Deviation 5.14	21.3 nM Standard Deviation 4.16	7.71 nM Standard Deviation 2.64	19.1 nM Standard Deviation 3.77	22.1 nM Standard Deviation 3.06	21.7 nM Standard Deviation 3.80	22.4 nM Standard Deviation 3.59	2.28 nM Standard Deviation 0.291	4.33 nM Standard Deviation 0.454	11.4 nM Standard Deviation 0.819	22.2 nM Standard Deviation 3.40	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Population: The analysis population consisted of participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment. Tmax was not estimated for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis.

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Tmax was not collected, analyzed or summarized for participants receiving placebo.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) n=6 Participants MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=5 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) n=6 Participants MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) n=6 Participants MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax)	3.5 Hours Interval 2.0 to 8.0	3.0 Hours Interval 2.0 to 4.0	4.0 Hours Interval 2.0 to 6.0	3.0 Hours Interval 2.0 to 4.0	1.5 Hours Interval 1.5 to 6.0	3.0 Hours Interval 2.0 to 10.0	5.0 Hours Interval 3.0 to 10.0	6.5 Hours Interval 2.0 to 15.0	9.0 Hours Interval 3.0 to 15.0	2.5 Hours Interval 1.5 to 4.0	4.0 Hours Interval 3.0 to 4.0	3.5 Hours Interval 2.0 to 4.0	4.0 Hours Interval 3.0 to 4.0	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Population: t1/2 was not estimated at MK-8266 doses below 1 mg and for the first 2 doses in Panel C due to the lack of measureable concentrations and for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis.

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. t1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. Harmonic means +/- Pseudo standard deviations are displayed. t1/2 was not collected, analyzed or summarized for participants receiving placebo.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) n=6 Participants MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n=5 Participants MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n=6 Participants MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) n=6 Participants MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
MK-8266 PK Parameter Apparent t1/2	11.7 Hours Standard Deviation 2.2	—	9.2 Hours Standard Deviation 3.5	12.0 Hours Standard Deviation 3.0	—	—	—	10.4 Hours Standard Deviation 2.2	12.8 Hours Standard Deviation 4.8	—	—	—	13.6 Hours Standard Deviation 2.6	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose

Population: All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model.

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC\[0-24 hours\] is a measure of the mean concentration levels of drug in the plasma after the dose. The Fed Group was administered a high fat meal.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
Effect of Food on MK-8266 PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24hr) Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants	—	—	—	—	—	—	—	—	—	59.6 nM·hr Interval 38.9 to 91.2	52.9 nM·hr Interval 34.6 to 81.0	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Population: All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model.

Outcome measures

Outcome measures
Measure	Panel A MK-8266 1.0/0.8 mg (Healthy Males) MK-826 6 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants	Panel B MK-8266 0.4 mg (Healthy Males) MK-8266 single dose 0.4 mg in healthy male participants	Panel B MK-8266 1.2 mg (Healthy Males) MK- 8266 single dose 1.2 mg in healthy male participants	Panel B MK-8266 1.2/0.6 mg (Healthy Males) MK-826 6 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants	Panel B MK-8266 0.4 mg Fed (Healthy Males) MK-8266 single 0.4 mg dose in healthy male participants, fed.	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel A MK-8266 0.1 mg (Healthy Males) n=6 Participants MK-826 6 single 0.1 mg dose in healthy male participants	Panel A MK-8266 0.2 mg (Healthy Males) n=6 Participants MK-826 6 single 0.2 mg dose in healthy male participants	Panel A MK-8266 0.5 mg (Healthy Males) MK-826 6 single 0.5 mg dose in healthy male participants	Panel A MK-8266 1.0 mg (Healthy Males) MK-826 6 single 1.0 mg dose in healthy male participants	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension	Panel C Placebo Placebo to MK-8266
Effect of Food on MK-8266 PK Parameter Cmax Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants	—	—	—	—	—	—	—	—	—	7.5 nM Interval 5.2 to 11.0	7.3 nM Interval 5.0 to 10.6	—	—	—	—

SECONDARY outcome

Timeframe: Up to 12 hours

HR was measured with a validated automatic measuring device. Time weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.