A Single Rising Dose Study of MK-8150 (MK-8150-001)
Condition: Hypertension; Isolated Systolic Hypertension (ISH)
MeSH terms: Hypertension; Isolated Systolic Hypertension
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Up to three planned panels (A, B and C) of either 8 healthy participants or 8 participants
      with mild to moderate hypertension will be enrolled. For Panel A and Panel B, dosing will
      occur in an alternating fashion between Panel A and Panel B with dosing commencing in Panel
      A. Participants will receive alternating single rising oral doses of MK-8150 or placebo in up
      to 5 treatment periods (Periods 1 through 5). Subsequent doses in any Panel will be
      administered only after careful evaluation of safety, tolerability, and pharmacodynamic
      effects of a given dose. For Panel C, participants will receive single rising oral doses of
      MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5). Depending on safety,
      tolerability and hemodynamic effects observed in the healthy participants, Panels A and/or B
      may be truncated and dosing may proceed in Panel C with hypertensive participants. In this
      case, dosing of hypertensive participants in Panel C will start with the second highest dose
      achieved in healthy participants.

      Amendment 1 of the protocol added Panel D (healthy males) based on the pharmacokinetic,
      pharmacodynamic and safety results from Panels A-C. Participants in Panel D will receive
      single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1
      through 5) at a dose range of 50 mg to 500 mg of MK-8150. Each treatment period will be
      approximately 3-4 days apart.
    

Intervention name(s): 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 type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment