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

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.

Time frame: 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.

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.

Time frame: 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. 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.

Time frame: 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. 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.

Time frame: 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. 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.

Time frame: 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.

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.

Time frame: Up to 43 days

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

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.

Time frame: 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.

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.

Time frame: 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. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. The Fed Group was administered a high fat meal.

Time frame: 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.

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.

Time frame: Up to 12 hours

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.