A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002 AM3)

• Number of Participants who Report an Adverse Event [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  
• Number of Participants Discontinued per Panel due to Meeting Hemodynamic Stopping Rules [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  
• 24-hour Time-weighted Average (TWA0-24hr) Change from Baseline in Central Systolic Blood Pressure (cSBP) [ Time Frame: Panels A-F and H: Predose, Day 1 (up to 24 hours postdose) and Day 10 (up to 24 hours postdose) and Panels G and I-J: Predose, Day 1 (up to 24 hours postdose) and Days 8, 15, 22, and 28 (up to 24 hours postdose) ] [ Designated as safety issue: No ]
  
• 24-hour Weighted Average Change from Baseline in Heart Rate (HR TWA0-24hrs) [ Time Frame: Panels A-F and H: Predose, Day 1 (up to 24 hours postdose) and Day 10 (up to 24 hours postdose) and Panels G and I-J: Predose, Day 1 (up to 24 hours postdose) and Days 8, 15, 22, and 28 (up to 24 hours postdose) ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Time-curve from Hour 0 to τ (where τ indicates the interval between doses [AUC(0-τ)]) of MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  
• Maximum Plasma Concentration (Cmax) of MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  
• Time to Cmax (Tmax) for MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  
• Apparent Terminal Half-life (t1/2) for MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  

Ten panels (Panels A-J), consisting of 104 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 me (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.