A Single Rising Dose Study of MK-8150 (MK-8150-001)

A Single Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01590810

Enrollment

Registered

2012-05-03

Start date

2012-05-07

Completion date

2013-02-05

Last updated

2018-09-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension, Isolated Systolic Hypertension (ISH)

Brief summary

This study will evaluate the safety and tolerability of MK-8150 and its effect on central systolic blood pressure (cSBP) and heart rate corrected augmentation index (AIx) when given as single oral doses in healthy males and in males with mild-to-moderate hypertension. A primary study hypothesis is that post dose mean change from baseline of time-weighted average across 24 hours (TWA0-24hrs) cSBP or AIx is reduced in participants administered MK-8150 compared to placebo in males with mild to moderate hypertension. A mean decrease from baseline compared to placebo of ≥5 mm Hg in TWA0-24hrs cSBP or of ≥5 percentage points in TWA0-24hrs AIx is considered clinically meaningful.

Detailed description

Up to three planned panels (A, B and C) of either 8 healthy participants or 8 participants with mild to moderate hypertension will be enrolled. For Panel A and Panel B, dosing will occur in an alternating fashion between Panel A and Panel B with dosing commencing in Panel A. Participants will receive alternating single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5). Subsequent doses in any Panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. For Panel C, participants will receive single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5). Depending on safety, tolerability and hemodynamic effects observed in the healthy participants, Panels A and/or B may be truncated and dosing may proceed in Panel C with hypertensive participants. In this case, dosing of hypertensive participants in Panel C will start with the second highest dose achieved in healthy participants. Amendment 1 of the protocol added Panel D (healthy males) based on the pharmacokinetic, pharmacodynamic and safety results from Panels A-C. Participants in Panel D will receive single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5) at a dose range of 50 mg to 500 mg of MK-8150. Each treatment period will be approximately 3-4 days apart.

Interventions

DRUGMK-8150 2.0 mg

Single oral 2.0-mg dose of MK-8150

DRUGMK-8150 10 mg

Single oral 10-mg dose of MK-8150

DRUGMK-8150 40 mg

Single oral 40-mg dose of MK-8150 without food (fasted) and with food (fed)

DRUGMK-8150 90 mg

Single oral 90-mg dose of MK-8150

DRUGMK-8150 5.0 mg

Single oral 5.0-mg dose of MK-8150

DRUGMK-8150 20 mg

Single oral 20-mg dose of MK-8150

DRUGMK-8150 60 mg

Single oral 60-mg dose of MK-8150

DRUGMK-8150 120 mg

Single oral 120-mg dose of MK-8150

DRUGMK-8150 160 mg

Single oral 160-mg dose of MK-8150

DRUGMK-8150 320 mg

Single oral 320-mg dose of MK-8150

DRUGMK-8150 600 mg

Single oral 600-mg dose of MK-8150

DRUGMK-8150 900 mg

Single oral 900-mg dose of MK-8150

DRUGMK-8150 1200 mg

Single oral 1200-mg dose of MK-8150

DRUGPlacebo for MK-8150

Single oral dose-matched dose of Placebo for MK-8150

DRUGMK-8150 50 mg

Single oral 50-mg dose of MK-8150

DRUGMK-8150 100 mg

Single oral 100-mg dose of MK-8150

DRUGMK-8150 200 mg

Single oral 200-mg dose of MK-8150

DRUGMK-8150 400 mg

Single oral 400-mg dose of MK-8150

DRUGMK-8150 500 mg

Single oral 500-mg dose of MK-8150

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* Between 18 and 50 years of age for Panels A, B and D, or between 18 and 60 years of age (inclusive) for Panel C. * Systolic blood pressure (SBP) \> 110 and ≤ 140 mmHg for Panels A, B, and D or SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication * Body Mass Index (BMI) ≥ 18 kg/m\^2 and ≤ 32 kg/m\^2 * Healthy (with the exception of hypertensive subjects in Panel C) * No clinically significant abnormality on electrocardiogram (ECG) * No history of clinically significant cardiac disease * No history of heart failure * Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months

Exclusion criteria

* Mentally or legally incapacitated * History of stroke, chronic seizures, or major neurological disorder * History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases * Functional disability that can interfere with rising from a sitting position to the standing position * History of neoplastic disease (cancer) * Unable to refrain from or anticipates the use of any medication during the study * Anticipates using medication for erectile dysfunction during the study * Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) * Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study * Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day * Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day * Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks * History of significant multiple and/or severe allergies (including latex allergy) * Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With an Adverse Event (AE)	Up to 14 days after the last dose (Up to approximately 42 days)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.
Number of Participants Who Discontinued Study Due to an AE	Up to 14 days after the last dose (Up to approximately 42 days)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.
Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP 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.
Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP 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.
Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP 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.
Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP 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.
Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose; except Period 1: Pre-dose and 2, 4, 12 and 24 hours post dose	AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx 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. AIx was adjusted for HR.
Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx 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. AIx was adjusted for HR.
Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx 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. AIx was adjusted for HR.
Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose	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.
Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx 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. AIx was adjusted for HR.
Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose	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.
Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose	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.
Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose	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.
Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP 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.
Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP 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.
Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP 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.
Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose	cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP 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.
Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP 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.
Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP 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.
Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP 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.
Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP 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.
Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP 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.
Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP 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.
Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP 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.
Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose	pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP 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.

Participant flow

Participants by arm

Arm	Count
Panel A - MK-8150 2 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel A, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel A was 2 mg to 90 mg.	8
Panel B - MK-8150 4 to 120 mg/Placebo Within each of the up to 5 treatment periods in Panel B, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel B was 4 mg to 120 mg.	8
Panel C - MK-8150 5 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel C, 6 participants with mild to moderate hypertension were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel C was 5 mg to 90 mg.	8
Panel D - MK-8150 50 to 200 mg Description: Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered MK-8150. The dose range of MK-8150 administered for Panel D was 50 mg to 200 mg.	8
Panel D - Placebo Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered placebo.	2
Total	34

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Physician Decision	0	1	1	0	0

Baseline characteristics

Characteristic	Panel A - MK-8150 2 to 90 mg/Placebo	Panel B - MK-8150 4 to 120 mg/Placebo	Panel C - MK-8150 5 to 90 mg/Placebo	Panel D - MK-8150 50 to 200 mg	Panel D - Placebo	Total
Age, Continuous	37.5 years STANDARD_DEVIATION 9.8	34.8 years STANDARD_DEVIATION 8	51.4 years STANDARD_DEVIATION 6.8	44.1 years STANDARD_DEVIATION 6.9	39.0 years STANDARD_DEVIATION 12.7	42 years STANDARD_DEVIATION 10
Augmentation Index (AIx)	7 percentage of central pulse pressure STANDARD_DEVIATION 3	8 percentage of central pulse pressure STANDARD_DEVIATION 4	22 percentage of central pulse pressure STANDARD_DEVIATION 8	10 percentage of central pulse pressure STANDARD_DEVIATION 11	8 percentage of central pulse pressure STANDARD_DEVIATION 12	12 percentage of central pulse pressure STANDARD_DEVIATION 9
Central Diastolic Blood Pressure (cDBP)	85 mm Hg STANDARD_DEVIATION 6	84 mm Hg STANDARD_DEVIATION 6	107 mm Hg STANDARD_DEVIATION 6	86 mm Hg STANDARD_DEVIATION 8	91 mm Hg STANDARD_DEVIATION 6	91 mm Hg STANDARD_DEVIATION 11
Central Systolic Blood Pressure (cSBP)	98 mm Hg STANDARD_DEVIATION 7	98 mm Hg STANDARD_DEVIATION 6	125 mm Hg STANDARD_DEVIATION 8	102 mm Hg STANDARD_DEVIATION 9	105 mm Hg STANDARD_DEVIATION 6	106 mm Hg STANDARD_DEVIATION 13
Heart Rate (HR)	58 beats per minute STANDARD_DEVIATION 7	54 beats per minute STANDARD_DEVIATION 5	67 beats per minute STANDARD_DEVIATION 9	61 beats per minute STANDARD_DEVIATION 7	45 beats per minute STANDARD_DEVIATION 1	59 beats per minute STANDARD_DEVIATION 9
Peripheral Diastolic Blood Pressure (pDBP)	75 mm Hg STANDARD_DEVIATION 6	73 mm Hg STANDARD_DEVIATION 6	94 mm Hg STANDARD_DEVIATION 6	75 mm Hg STANDARD_DEVIATION 8	80 mm Hg STANDARD_DEVIATION 7	79 mm Hg STANDARD_DEVIATION 10
Peripheral Systolic Blood Pressure (pSBP)	119 mm Hg STANDARD_DEVIATION 5	119 mm Hg STANDARD_DEVIATION 6	148 mm Hg STANDARD_DEVIATION 7	125 mm Hg STANDARD_DEVIATION 8	126 mm Hg STANDARD_DEVIATION 12	128 mm Hg STANDARD_DEVIATION 14
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	8 Participants	8 Participants	8 Participants	8 Participants	2 Participants	34 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	8 / 8	8 / 8	7 / 8	7 / 8	2 / 2
serious Total, serious adverse events	0 / 8	0 / 8	0 / 8	0 / 8	0 / 2

Outcome results

Primary

Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

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.

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

Population: Per-Protocol population. 2 participants received placebo in period of fasted administration of MK-8150 24 mg dose and again received placebo during the period of fed administration of that dose. Data for both administrations of placebo in these participants are included (i.e., for placebo, analysis includes 10 observations from 8 participants)

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	2.94 beats per minute	Standard Error 1.31
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	4.08 beats per minute	Standard Error 1.61
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	4.07 beats per minute	Standard Error 1.47
Panel D - MK-8150 50 to 200 mg	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	7.54 beats per minute	Standard Error 2.19
Panel D - Placebo	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	4.04 beats per minute	Standard Error 1.65
Panel A - Placebo	Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	1.89 beats per minute	Standard Error 1.43

p-value: 0.17595% CI: [-0.5, 2.6]Mixed Models Analysis

p-value: 0.07695% CI: [-0.25, 4.61]Mixed Models Analysis

p-value: 0.00195% CI: [1.04, 3.32]Mixed Models Analysis

p-value: <0.000195% CI: [3.14, 8.15]Mixed Models Analysis

p-value: 0.00895% CI: [0.63, 3.67]Mixed Models Analysis

Primary

Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP 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.

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	1.33 mm Hg	Standard Error 0.99
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-1.65 mm Hg	Standard Error 1.31
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-7.69 mm Hg	Standard Error 1.71
Panel D - MK-8150 50 to 200 mg	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-6.29 mm Hg	Standard Error 1.82
Panel D - Placebo	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-9.86 mm Hg	Standard Error 1.66
Panel A - Placebo	Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	0.55 mm Hg	Standard Error 1.08

p-value: 0.50395% CI: [-1.59, 3.15]Mixed Models Analysis

p-value: <0.000195% CI: [-2.86, -1.55]Mixed Models Analysis

p-value: <0.000195% CI: [-10.13, -6.34]Mixed Models Analysis

p-value: <0.000195% CI: [-9.1, -4.58]Mixed Models Analysis

p-value: <0.000195% CI: [-12.89, -7.92]Mixed Models Analysis

Primary

Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

Population: Per-Protocol population. 2 participants received placebo in period of initial administration of MK-8150 120 mg dose and again received placebo during the period of repeat administration of that dose. Data for both administrations of placebo in these participants are included (i.e., for placebo, analysis includes 10 observations from 8 participants)

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-0.26 beats per minute	Standard Error 1.1
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-0.91 beats per minute	Standard Error 1.57
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	0.66 beats per minute	Standard Error 1.75
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	3.17 beats per minute	Standard Error 0.91
Panel D - Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	5.19 beats per minute	Standard Error 1.45
Panel A - Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	0.57 beats per minute	Standard Error 1.16

p-value: 0.55795% CI: [-3.7, 2.05]Mixed Models Analysis

p-value: 0.17595% CI: [-3.65, 0.7]Mixed Models Analysis

p-value: 0.95195% CI: [-3.04, 3.23]Mixed Models Analysis

p-value: <0.00195% CI: [1.34, 3.88]Mixed Models Analysis

p-value: <0.000195% CI: [3, 6.24]Mixed Models Analysis

Primary

Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

Population: Per-Protocol population. The same 2 participants received placebo throughout all treatment periods of Panel D. Data for all administrations of placebo in these participants are included (i.e., for placebo, analysis includes 8 observations from 2 participants)

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-1.24 beats per minute	Standard Error 1.9
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-1.09 beats per minute	Standard Error 2.15
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-0.52 beats per minute	Standard Error 1.59
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	3.83 beats per minute	Standard Error 2.15
Panel D - Placebo	Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-5.67 beats per minute	Standard Error 3.66

p-value: 0.38595% CI: [-5.96, 14.81]Mixed Models Analysis

p-value: 0.38595% CI: [-6.16, 15.32]Mixed Models Analysis

p-value: 0.27695% CI: [-4.44, 14.74]Mixed Models Analysis

p-value: 0.06995% CI: [-0.81, 19.81]Mixed Models Analysis

Primary

Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-6.11 beats per minute	Standard Error 2.32
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-3.74 beats per minute	Standard Error 1.58
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-1.02 beats per minute	Standard Error 1.75
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-4.67 beats per minute	Standard Error 2.23

p-value: 0.24195% CI: [-4.01, 1.12]Mixed Models Analysis

p-value: 0.66495% CI: [-3.63, 5.48]Mixed Models Analysis

p-value: 0.11495% CI: [-1.03, 8.33]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx 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. AIx was adjusted for HR.

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose; except Period 1: Pre-dose and 2, 4, 12 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-0.75 percentage of central pulse pressure	Standard Error 1.99
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-0.67 percentage of central pulse pressure	Standard Error 1.63
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-10.06 percentage of central pulse pressure	Standard Error 1.62
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-6.59 percentage of central pulse pressure	Standard Error 2.22
Panel D - Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-15.22 percentage of central pulse pressure	Standard Error 1.53
Panel A - Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	1.56 percentage of central pulse pressure	Standard Error 1.32

p-value: 0.06195% CI: [-4.73, 0.11]Mixed Models Analysis

p-value: 0.01695% CI: [-4, -0.45]Mixed Models Analysis

p-value: <0.000195% CI: [-14.42, -8.82]Mixed Models Analysis

p-value: <0.000195% CI: [-11.34, -4.96]Mixed Models Analysis

p-value: <0.000195% CI: [-20.81, -12.75]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-3.04 percentage of central pulse pressure	Standard Error 1.55
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-6.85 percentage of central pulse pressure	Standard Error 1.83
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-13.57 percentage of central pulse pressure	Standard Error 2.54
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-18.42 percentage of central pulse pressure	Standard Error 1.55
Panel D - Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-16.33 percentage of central pulse pressure	Standard Error 2.22
Panel A - Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-0.09 percentage of central pulse pressure	Standard Error 1.5

p-value: 0.02995% CI: [-5.56, -0.34]Mixed Models Analysis

p-value: 0.00595% CI: [-11.29, -2.22]Mixed Models Analysis

p-value: <0.00195% CI: [-20.03, -6.93]Mixed Models Analysis

p-value: <0.000195% CI: [-21.98, -14.68]Mixed Models Analysis

p-value: <0.000195% CI: [-20.29, -12.19]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-13.83 percentage of central pulse pressure	Standard Error 1.54
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-12.04 percentage of central pulse pressure	Standard Error 1.46
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.09 percentage of central pulse pressure	Standard Error 1.12
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-14.42 percentage of central pulse pressure	Standard Error 1.29
Panel D - Placebo	Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-1.46 percentage of central pulse pressure	Standard Error 0.17

p-value: <0.000195% CI: [-15.62, -9.11]Mixed Models Analysis

p-value: <0.000195% CI: [-13.74, -7.42]Mixed Models Analysis

p-value: <0.000195% CI: [-16.12, -11.13]Mixed Models Analysis

p-value: <0.000195% CI: [-15.85, -10.08]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-8.32 percentage of central pulse pressure	Standard Error 1.69
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-12.09 percentage of central pulse pressure	Standard Error 3.25
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-21.03 percentage of central pulse pressure	Standard Error 1.9
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-6.73 percentage of central pulse pressure	Standard Error 2.49

p-value: 0.53995% CI: [-7.12, 3.93]Mixed Models Analysis

p-value: 0.11395% CI: [-12.23, 1.5]Mixed Models Analysis

p-value: <0.00195% CI: [-19.69, -8.91]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP 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.

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	0.74 mm Hg	Standard Error 1.07
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-1.97 mm Hg	Standard Error 1.46
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-8.34 mm Hg	Standard Error 1.77
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-6.73 mm Hg	Standard Error 2.27
Panel D - Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-10.54 mm Hg	Standard Error 1.62
Panel A - Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-0.23 mm Hg	Standard Error 1.11

p-value: 0.38395% CI: [-1.28, 3.22]Mixed Models Analysis

p-value: 0.00295% CI: [-2.79, -0.7]Mixed Models Analysis

p-value: <0.000195% CI: [-10.08, -6.14]Mixed Models Analysis

p-value: <0.00195% CI: [-9.74, -3.25]Mixed Models Analysis

p-value: <0.000195% CI: [-12.84, -7.78]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-5.02 mm Hg	Standard Error 1.1
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-7.76 mm Hg	Standard Error 1.61
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-11.88 mm Hg	Standard Error 1.75
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-14.12 mm Hg	Standard Error 1.95
Panel D - Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-12.21 mm Hg	Standard Error 1.3
Panel A - Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-2.96 mm Hg	Standard Error 1.33

p-value: 0.21695% CI: [-5.43, 1.3]Mixed Models Analysis

p-value: 0.04695% CI: [-9.51, -0.1]Mixed Models Analysis

p-value: 0.00295% CI: [-14.1, -3.76]Mixed Models Analysis

p-value: <0.00195% CI: [-16.64, -5.68]Mixed Models Analysis

p-value: <0.000195% CI: [-12.7, -5.8]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.55 mm Hg	Standard Error 1.05
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-13.26 mm Hg	Standard Error 0.93
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.35 mm Hg	Standard Error 1.19
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.84 mm Hg	Standard Error 1.1
Panel D - Placebo	Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-4.71 mm Hg	Standard Error 0.52

p-value: <0.000195% CI: [-13.79, -7.89]Mixed Models Analysis

p-value: <0.000195% CI: [-11.18, -5.91]Mixed Models Analysis

p-value: <0.000195% CI: [-13.44, -7.84]Mixed Models Analysis

p-value: <0.000195% CI: [-13.97, -8.29]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-10.40 mm Hg	Standard Error 1.96
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-16.32 mm Hg	Standard Error 3.97
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-23.65 mm Hg	Standard Error 2.67
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-8.14 mm Hg	Standard Error 3.76

p-value: 0.63595% CI: [-12.5, 7.96]Mixed Models Analysis

p-value: 0.14395% CI: [-19.58, 3.22]Mixed Models Analysis

p-value: 0.00495% CI: [-25.01, -6.01]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-5.06 mm Hg	Standard Error 0.91
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-7.64 mm Hg	Standard Error 1.5
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-11.67 mm Hg	Standard Error 1.68
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-14.20 mm Hg	Standard Error 1.6
Panel D - Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-11.91 mm Hg	Standard Error 1.26
Panel A - Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-2.18 mm Hg	Standard Error 1.11

p-value: 0.05295% CI: [-5.79, 0.02]Mixed Models Analysis

p-value: 0.0195% CI: [-9.49, -1.43]Mixed Models Analysis

p-value: <0.00195% CI: [-14.2, -4.79]Mixed Models Analysis

p-value: <0.000195% CI: [-16.51, -7.52]Mixed Models Analysis

p-value: <0.000195% CI: [-12.93, -6.53]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-16.23 mm Hg	Standard Error 1.4
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-13.22 mm Hg	Standard Error 1.55
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.84 mm Hg	Standard Error 1.5
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-15.86 mm Hg	Standard Error 1.47
Panel D - Placebo	Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-3.02 mm Hg	Standard Error 0.38

p-value: <0.000195% CI: [-16.84, -9.59]Mixed Models Analysis

p-value: <0.000195% CI: [-13.94, -6.45]Mixed Models Analysis

p-value: <0.000195% CI: [-16.45, -9.19]Mixed Models Analysis

p-value: <0.000195% CI: [-16.49, -9.19]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-11.69 mm Hg	Standard Error 3.01
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-18.38 mm Hg	Standard Error 4.47
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-25.11 mm Hg	Standard Error 3.2
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-7.60 mm Hg	Standard Error 4.46

p-value: 0.4895% CI: [-16.44, 8.25]Mixed Models Analysis

p-value: 0.08695% CI: [-23.37, 1.79]Mixed Models Analysis

p-value: 0.00695% CI: [-28.85, -6.18]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP 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.

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-0.92 mm Hg	Standard Error 0.61
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-2.58 mm Hg	Standard Error 1.13
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-8.01 mm Hg	Standard Error 1.56
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-6.69 mm Hg	Standard Error 2.3
Panel D - Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-9.85 mm Hg	Standard Error 1.38
Panel A - Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-1.24 mm Hg	Standard Error 0.9

p-value: 0.76595% CI: [-1.82, 2.45]Mixed Models Analysis

p-value: 0.02395% CI: [-2.49, -0.2]Mixed Models Analysis

p-value: <0.000195% CI: [-9.18, -4.36]Mixed Models Analysis

p-value: 0.0195% CI: [-9.46, -1.44]Mixed Models Analysis

p-value: <0.000195% CI: [-11.28, -5.94]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-3.91 mm Hg	Standard Error 1.02
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-6.21 mm Hg	Standard Error 1.34
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-9.64 mm Hg	Standard Error 1.86
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-11.69 mm Hg	Standard Error 1.85
Panel D - Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-10.20 mm Hg	Standard Error 1.11
Panel A - Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-1.90 mm Hg	Standard Error 0.85

p-value: 0.1695% CI: [-4.89, 0.86]Mixed Models Analysis

p-value: 0.03995% CI: [-8.4, -0.24]Mixed Models Analysis

p-value: 0.00395% CI: [-12.58, -2.92]Mixed Models Analysis

p-value: <0.00195% CI: [-14.49, -5.09]Mixed Models Analysis

p-value: <0.000195% CI: [-11.3, -5.31]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-13.91 mm Hg	Standard Error 0.77
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-11.65 mm Hg	Standard Error 0.61
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-13.36 mm Hg	Standard Error 0.87
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-14.31 mm Hg	Standard Error 0.87
Panel D - Placebo	Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-4.79 mm Hg	Standard Error 1.17

p-value: <0.000195% CI: [-12.22, -6.03]Mixed Models Analysis

p-value: <0.000195% CI: [-9.73, -3.99]Mixed Models Analysis

p-value: <0.000195% CI: [-11.51, -5.64]Mixed Models Analysis

p-value: <0.000195% CI: [-12.55, -6.5]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-7.87 mm Hg	Standard Error 1.89
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-12.90 mm Hg	Standard Error 3.55
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-19.82 mm Hg	Standard Error 2.27
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-6.14 mm Hg	Standard Error 3.8

p-value: 0.00695% CI: [-22.55, -4.81]Mixed Models Analysis

p-value: 0.67595% CI: [-10.54, 7.09]Mixed Models Analysis

p-value: 0.17495% CI: [-16.98, 3.46]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP 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.

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	0.73 mm Hg	Standard Error 1.35
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-0.24 mm Hg	Standard Error 1.45
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-3.13 mm Hg	Standard Error 1.56
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-1.91 mm Hg	Standard Error 1.42
Panel D - Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	-4.46 mm Hg	Standard Error 1.7
Panel A - Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)	1.46 mm Hg	Standard Error 1.41

p-value: 0.54795% CI: [-3.19, 1.73]Mixed Models Analysis

p-value: 0.00495% CI: [-2.79, -0.62]Mixed Models Analysis

p-value: <0.000195% CI: [-6.23, -2.94]Mixed Models Analysis

p-value: <0.00195% CI: [-4.98, -1.76]Mixed Models Analysis

p-value: <0.000195% CI: [-8.24, -3.59]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-4.61 mm Hg	Standard Error 1
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-6.81 mm Hg	Standard Error 1.61
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-7.16 mm Hg	Standard Error 2
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-8.50 mm Hg	Standard Error 1.39
Panel D - Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-6.40 mm Hg	Standard Error 1.19
Panel A - Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)	-1.17 mm Hg	Standard Error 1.01

p-value: 0.01795% CI: [-6.19, -0.67]Mixed Models Analysis

p-value: <0.00195% CI: [-8.43, -2.84]Mixed Models Analysis

p-value: 0.00595% CI: [-9.94, -2.04]Mixed Models Analysis

p-value: <0.00195% CI: [-10.9, -3.76]Mixed Models Analysis

p-value: <0.00195% CI: [-7.76, -2.69]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-12.77 mm Hg	Standard Error 1.14
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-10.19 mm Hg	Standard Error 1.86
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-11.19 mm Hg	Standard Error 1.78
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-10.47 mm Hg	Standard Error 1.79
Panel D - Placebo	Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)	-3.00 mm Hg	Standard Error 0.85

p-value: <0.000195% CI: [-12.9, -6.65]Mixed Models Analysis

p-value: 0.00395% CI: [-11.57, -2.81]Mixed Models Analysis

p-value: 0.00195% CI: [-12.4, -3.98]Mixed Models Analysis

p-value: 0.00195% CI: [-11.69, -3.25]Mixed Models Analysis

Primary

Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

Population: Per-Protocol population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Panel A - MK-8150 2 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-12.32 mm Hg	Standard Error 3.88
Panel B - MK-8150 4 to 120 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-18.26 mm Hg	Standard Error 4.84
Panel C - MK-8150 5 to 90 mg/Placebo	Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-21.42 mm Hg	Standard Error 3.63
Panel D - MK-8150 50 to 200 mg	Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)	-5.39 mm Hg	Standard Error 6.63

p-value: 0.31195% CI: [-21.27, 7.42]Mixed Models Analysis

p-value: 0.07895% CI: [-27.44, 1.69]Mixed Models Analysis

p-value: 0.02795% CI: [-29.87, -2.19]Mixed Models Analysis

Primary

Number of Participants Who Discontinued Study Due to an AE

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

Time frame: Up to 14 days after the last dose (Up to approximately 42 days)

Population: All participants who received a dose of study drug

Arm	Measure	Value (NUMBER)
Panel A - MK-8150 2 to 90 mg/Placebo	Number of Participants Who Discontinued Study Due to an AE	0 participants
Panel B - MK-8150 4 to 120 mg/Placebo	Number of Participants Who Discontinued Study Due to an AE	0 participants
Panel C - MK-8150 5 to 90 mg/Placebo	Number of Participants Who Discontinued Study Due to an AE	0 participants
Panel D - MK-8150 50 to 200 mg	Number of Participants Who Discontinued Study Due to an AE	0 participants
Panel D - Placebo	Number of Participants Who Discontinued Study Due to an AE	0 participants

Primary

Number of Participants With an Adverse Event (AE)

Time frame: Up to 14 days after the last dose (Up to approximately 42 days)

Population: All participants who received a dose of study drug

Arm	Measure	Value (NUMBER)
Panel A - MK-8150 2 to 90 mg/Placebo	Number of Participants With an Adverse Event (AE)	8 participants
Panel B - MK-8150 4 to 120 mg/Placebo	Number of Participants With an Adverse Event (AE)	8 participants
Panel C - MK-8150 5 to 90 mg/Placebo	Number of Participants With an Adverse Event (AE)	7 participants
Panel D - MK-8150 50 to 200 mg	Number of Participants With an Adverse Event (AE)	7 participants
Panel D - Placebo	Number of Participants With an Adverse Event (AE)	2 participants

Source: ClinicalTrials.gov · Data processed: Mar 1, 2026

A Single Rising Dose Study of MK-8150 (MK-8150-001)

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

Number of Participants Who Discontinued Study Due to an AE

Number of Participants With an Adverse Event (AE)