A Single Rising Dose Study of MK-8150 (MK-8150-001)
Condition: Hypertension; Isolated Systolic Hypertension (ISH)
MeSH terms: Hypertension; Isolated Systolic Hypertension
Intervention: MK-8150 2.0 mg; MK-8150 10 mg; MK-8150 40 mg; MK-8150 90 mg; MK-8150 5.0 mg; MK-8150 20 mg; MK-8150 60 mg; MK-8150 120 mg; MK-8150 160 mg; MK-8150 320 mg; MK-8150 600 mg; MK-8150 900 mg; MK-8150 1200 mg; Placebo for MK-8150; MK-8150 50 mg; MK-8150 100 mg; MK-8150 200 mg; MK-8150 400 mg; MK-8150 500 mg
Intervention description: Single oral 2.0-mg dose of MK-8150; Single oral 10-mg dose of MK-8150; Single oral 40-mg dose of MK-8150 without food (fasted) and with food (fed); Single oral 90-mg dose of MK-8150; Single oral 5.0-mg dose of MK-8150; Single oral 20-mg dose of MK-8150; Single oral 60-mg dose of MK-8150; Single oral 120-mg dose of MK-8150; Single oral 160-mg dose of MK-8150; Single oral 320-mg dose of MK-8150; Single oral 600-mg dose of MK-8150; Single oral 900-mg dose of MK-8150; Single oral 1200-mg dose of MK-8150; Single oral dose-matched dose of Placebo for MK-8150; Single oral 50-mg dose of MK-8150; Single oral 100-mg dose of MK-8150; Single oral 200-mg dose of MK-8150; Single oral 400-mg dose of MK-8150; Single oral 500-mg dose of MK-8150
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 34.0
Sex: Male
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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