Safety, Tolerability, and Pharmacokinetics of MK-8266 in Elderly Participants With High Blood Pressure (MK-8266-003)

This is a randomized, double-blind, placebo-controlled study. The hypothesis for this study is that single oral doses of MK-8266 selected for this study are sufficiently safe and well tolerated by elderly male and elderly female participants with hypertension to permit continued clinical investigation.

Two panels, each consisting of eight participants (8 elderly males with mild to moderate hypertension in Panel A and 8 elderly females with mild to moderate hypertension in Panel B) will be randomized to receive either MK-8266 or matching placebo in a 3:1 ratio. Participants will receive single doses of MK-8266 or matching placebo in three treatment periods (Periods 1 through 3). In both Panel A and Panel B, doses will escalate in a rising, fixed sequence. In Period 1 (0.3 mg), Period 2 (0.6 mg), and Period 3 (0.7 mg and then 0.3 mg 10 hours later) once daily doses of MK-8266 or matching placebo will be administered.

All participants will receive at least 2 doses of MK-8266. Participants completing placebo treatment in Period 1 will flow to the MK-8266 arm in the next period, with 2 participants from the MK-8266 arm receiving placebo in the next period.

Blood samples will be obtained pre-dose and at selected time points up to 48 hours post-dose for determination of MK-8266 plasma concentrations.

Eligibility Criteria:
Inclusion criteria:

* Participants are male or non-childbearing female.
* Participant with essential hypertension (HTN), Grade 1 or 2 (as per European Society of Hypertension \[ESH\]) or isolated mild to moderate systolic HTN. High normal systolic BP ≥130 mmHg will be also allowed. Blood pressures to be confirmed on at least three occasions pre-study. The possibility of secondary causes of HTN should be assessed. Participants who are being treated for HTN with drugs (including beta blocking medications) may be able to participate if the drug doses can be reduced or discontinued, at the discretion of the investigator.
* Participants with a Body Mass Index (BMI) ≤35 kg/m\^2 at the screening visit.
* Participants judged to be generally in good health based on medical history, physical examination, vital sign measurements (with the exception of HTN), and laboratory safety tests performed at the screening visit.
* Participant has no clinically significant abnormality (confirmed by the investigator in consultation with the Merck Clinical Monitor) on electrocardiogram (ECG) or Holter Monitor Evaluation performed at the screening visit and/or prior to administration of the initial dose of study drug.
* Participants must have a platelet count ≥150,000 cu/mL at the screening and pre-study visit.
* Participants, at screening, will have a positive Augmentation Index.
* Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months; participants who have discontinued smoking or the use of nicotine/nicotine containing products for at least 3 months may be enrolled at the discretion of the investigator.
* Participant is willing to comply with the study restrictions.
* Participant has a negative test for hidden blood in the stool at screening.

Exclusion criteria:

* Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
* Participant has an estimated creatinine clearance of ≤60 mL/min based on the Cockcroft-Gault equation.
* Participant has a history of stroke, chronic seizures, or major neurological disorder.
* Participant has a history of clinically significant endocrine, gastrointestinal, cardiovascular (with the exception of HTN), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases. Participants with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the study at the discretion of the investigator.
* Patient demonstrates low blood pressure at screening and Pre-dose Day 1 while going from a semi-recumbent to standing position.
* Participant has a functional disability that can interfere with rising from a semi-recumbent position to the standing position.
* Participant has any personal or family history of a bleeding or a clotting disorder.
* Participant has a history of frequent nosebleeds.
* Participant has a history of cancer with the exceptions of: adequately treated non-melanoma skin carcinoma or carcinoma in situ of the cervix; other malignancies which have been successfully treated \>10 years prior to the screening visit, for which in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the screening visit; or, participants, who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study.
* Participant has a history of clinically significant cardiac disease including, but not limited to hemodynamically relevant heart valve disease (if there would be any uncertainty about the diagnosis, confirmation with an echocardiography within 3 months of screening is required), or evidence of secondary cardiac damage.
* Participant is categorized as a class II or greater functional classification for heart failure according to the New York Heart Association (NYHA).
* Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort \[Hypericum perforatum\]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study until the post-study visit. Certain medication use may be permitted after consultation with the Merck clinical monitor.
* Participant currently and regularly uses aspirin (including low dose) and cannot be discontinued from it from 2 weeks prior to study start or has used aspirin within 2 weeks prior to study start (and anticipates using it during the course of the study); this applies also to any pain relievers and cold or sinus remedies that have aspirin in them, and the use of anti-platelet drugs, such as clopidogrel or dipyridamole. Chronic use of certain non-steroidal anti-inflammatory drugs (NSAIDs) such as ≥500 mg of naproxen twice a day must be also avoided beginning at least 2 weeks prior the study and until the post-study visit.
* Participant anticipates using sildenafil (Viagra®), tadalafil (Cialis®), or Vardenafil (Levitra®).
* Participant uses or anticipates using organic nitrate preparations (for example, nitroglycerin, isosorbide mononitrate, isosorbide dinitrate or pentaerythritol) during the course of the study.
* Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day. Participants that consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.
* Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day.
* Participant has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the screening visit. The 4-week window will be derived from the date of the last study procedure (i.e., post-study, AE follow-up, etc.) in the previous study to the screening visit of the current study.
* Participant has a history of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
* Participant is currently a regular user of illicit drugs or has a history of drug/alcohol abuse within approximately 1 year of the screening visit.