Clinical trial NCT01656408
Conditions: Hypertension Isolated Systolic Hypertension
Sponsor: Merck Sharp & Dohme LLC
Start date: 2012-08-01; Completion date: 2013-05-23
Enrollment: 103 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: MK-8150 or matching placebo once daily, capsules, oral, for 10 days arm 2: MK-8150 or matching placebo once daily, capsules, oral, for 10 days arm 3: MK-8150 or matching placebo once daily, capsules, oral, for 10 days arm 4: MK-8150 or matching placebo once daily, capsules, oral, for 10 days arm 5: Single dose of MK-8150 or placebo on Study Day 1 followed by a wash-out of at least 5 days, then MK-8150 or placebo once daily at a lower dose for 10 days arm 6: Single dose of MK-8150 or placebo on Study Day 1 followed by a wash-out of at least 5 days, then MK-8150 or placebo once daily at a lower dose for 10 days arm 7: MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22. arm 8: MK-8150 or matching placebo for 10 consecutive days in 2-period crossover with minimum 3 weeks washout period between the 2 treatment periods arm 9: MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22. arm 10: MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22.
Interventions: intervention 1: MK-8150 intervention 2: Placebo for MK-8150
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents: