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

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.

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.

Eligibility Criteria:
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