A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002)
Condition: Hypertension; Isolated Systolic Hypertension
MeSH terms: Hypertension; Isolated Systolic Hypertension
Intervention: MK-8150; Placebo for MK-8150
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 103.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This randomized, double-blind, placebo-controlled, multiple-rising-dose study will evaluate
      the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-8150 in healthy young
      men, in male participants with mild to moderate hypertension, in elderly male and female
      participants with mild to moderate hypertension, and in male and female participants with
      resistant hypertension. A primary study hypothesis is that there is at least one dose that
      does not increase heart rate (HR) to a clinically meaningful extent in male participants with
      mild to moderate hypertension and in elderly participants with mild to moderate hypertension
      on either Day 1 or the last Day of multiple dosing (Daylast), as measured by Time-weighted
      Average Across 24 hours (TWA0-24hrs). The hypothesis is met if mean increase (MK-8150 -
      placebo) in TWA0-24hrs HR in the identified groups is ≤15 beats per minute on Day 1 and
      Daylast.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Hypertensive male participant between 18 to 55 years of age for Panels A to D;
             hypertensive male or female of non-childbearing potential between 65 to 80 years of
             age for Panels E and F; healthy males between 18 to 55 years of age for Panel G;
             hypertensive male or non-childbearing potential female between 18 to 65 years of age
             (inclusive) for Panel H; hypertensive male between 18 to 65 years of age for Panels I
             and J

          -  Body Mass Index (BMI) ≤ 33 kg/m^2

          -  In good age appropriate health

          -  No history of clinically significant cardiac disease

          -  Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6
             months

        Exclusion Criteria:

          -  Mentally or legally incapacitated, has significant emotional problems or has a history
             of a clinically significant psychiatric disorder over the last 5 years

          -  History of stroke, chronic seizures, or a relevant major neurological disorder

          -  History of neoplastic disease (cancer)

          -  Unable to refrain from or anticipates the use of any medication, including any
             non-steroidal anti-inflammatory drug (NSAID) and aspirin-containing products,
             prescription and non-prescription drugs or herbal remedies for 2 weeks prior to study
             start up to end of study

          -  Anticipates using erectile dysfunction medications during the study

          -  Uses or anticipates using organic nitrates during the course of the study (e.g.
             nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)

          -  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

          -  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)

          -  Current regular user (including recreational use) of any illicit drugs or has a
             history of drug (including alcohol) abuse within approximately 1 year