Safety, Tolerability, and Pharmacokinetics of MK-8266 in Elderly Participants With High Blood Pressure (MK-8266-003)
Condition: Hypertension
MeSH terms: Hypertension
Intervention: MK-8266; Placebo
Intervention description: Oral capsules, 0.1 mg potency; Oral placebo capsules to match MK-8266 capsules
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 65 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Hypertension

Summary:

      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.
    

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.