A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)

This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).

Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-8892 or placebo. All doses will be administered in the fasted state, except Panel A, Period 5 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing.

Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. Panel C may begin after the first 4 periods of Panels A and B have completed dosing. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. Subsequent doses in any panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. All participants in periods of all panels (with exception of 2.0 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 2.0 mg MK-8892 in a fasted and fed state.The 2.0 mg MK-8892 fed/fasted data will be utilized for pharmacokinetic comparison and only the 2.0 mg MK-8892 fasted data will utilized for the analysis of the pharmacodynamics endpoints.

In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥1 hour, dose escalation in that participant will be halted and the participant may be withdrawn from the study or rechallenged at same dose or at a lower dose. Paricipants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.

Eligibility Criteria:
Inclusion Criteria:

* Systolic blood pressure (SBP) \> 110 and ≤ 140 mmHg for Panels A and B, 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 cancer (malignancy)
* History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
* Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)
* Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
* Has participated in another investigational trial within 4 weeks
* 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
* Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year