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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Ten panels (Panels A-J), consisting of 103 participants in total, will be randomized to
      receive either MK-8150 or matching placebo.

      Males (18 to 55 years of age, inclusive) with mild to moderate hypertension will be
      randomized in Panels A-D and will receive either MK-8150 or placebo as once daily treatment
      for 10 consecutive days.

      Elderly males and females (65 to 80 years of age, inclusive) with mild to moderate
      hypertension will be included in Panels E and F and will receive a single dose of either
      MK-8150 or placebo on Study Day 1 followed by at least 5 days of wash-out before proceeding
      to once daily treatment of the same randomized treatment at a lower dose for 10 consecutive
      days.

      Participants 18 to 65 years of age with resistant hypertension will be enrolled in Panels H
      and will receive in randomized sequences of MK-8150/placebo or placebo/MK-8150 in 2 treatment
      periods. There will be a minimum 3 weeks washout period between the 2 treatment periods in
      Panel H.

      Healthy males (18 to 55 years of age, inclusive) will be enrolled in Panel G and will receive
      MK-8150 or matching placebo once daily for 28 days. Participants randomized to MK-8150 in
      Panel G who meet all of the dose-escalation criteria and have not met any of the hemodynamic
      stopping criteria will be eligible for dose increases on Day 8, Day 15, and Day 22. If dose
      escalation criteria are not met (or if the Investigator or Sponsor elects not to increase the
      dose), then the participant will continue on the current dose and will be eligible for a dose
      increase at the next dose-escalation decision day if all dose-escalation criteria are met at
      that time.

      Male participants (18 to 65 years of age, inclusive) with mild to moderate hypertension will
      be randomized in Panels I and J. In each panel, 18 participants will receive either MK-8150
      or matching placebo as once daily treatment for up to 28 consecutive days. Participants who
      are randomized to placebo will receive placebo throughout the study. On Days 8, 15 and 22 in
      both Panels I and J, participants will be eligible for dose-escalation, down-dosing, or
      continuing their current dose depending on their hemodynamic status. Participants in Panels I
      and J who meet down-dosing criteria at any time during the study will have their doses
      reduced to the previous well-tolerated dose level until the next dose-escalation decision
      day, or through the end of the study, whichever is first.
    

Intervention name(s): MK-8150; Placebo for MK-8150
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment