Clinical trial NCT01590810
Conditions: Hypertension Isolated Systolic Hypertension (ISH)
Sponsor: Merck Sharp & Dohme LLC
Start date: 2012-05-07; Completion date: 2013-02-05
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel A will be 2.0 mg to 90 mg. arm 2: Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel B will be 5.0 mg to 160 mg. arm 3: Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel C will be 160 mg to 1200 mg. arm 4: Within each panel, 8 subjects will be randomly assigned to MK-8150 and 2 subjects will be randomly assigned to placebo throughout the 5 periods according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel D will be 50 mg to 500 mg.
Interventions: intervention 1: MK-8150 2.0 mg intervention 2: MK-8150 10 mg intervention 3: MK-8150 40 mg intervention 4: MK-8150 90 mg intervention 5: MK-8150 5.0 mg intervention 6: MK-8150 20 mg intervention 7: MK-8150 60 mg intervention 8: MK-8150 120 mg intervention 9: MK-8150 160 mg intervention 10: MK-8150 320 mg intervention 11: MK-8150 600 mg intervention 12: MK-8150 900 mg intervention 13: MK-8150 1200 mg intervention 14: Placebo for MK-8150 intervention 15: MK-8150 50 mg intervention 16: MK-8150 100 mg intervention 17: MK-8150 200 mg intervention 18: MK-8150 400 mg intervention 19: MK-8150 500 mg
Intervention descriptions: intervention 1: Single oral 2.0-mg dose of MK-8150 intervention 2: Single oral 10-mg dose of MK-8150 intervention 3: Single oral 40-mg dose of MK-8150 without food (fasted) and with food (fed) intervention 4: Single oral 90-mg dose of MK-8150 intervention 5: Single oral 5.0-mg dose of MK-8150 intervention 6: Single oral 20-mg dose of MK-8150 intervention 7: Single oral 60-mg dose of MK-8150 intervention 8: Single oral 120-mg dose of MK-8150 intervention 9: Single oral 160-mg dose of MK-8150 intervention 10: Single oral 320-mg dose of MK-8150 intervention 11: Single oral 600-mg dose of MK-8150 intervention 12: Single oral 900-mg dose of MK-8150 intervention 13: Single oral 1200-mg dose of MK-8150 intervention 14: Single oral dose-matched dose of Placebo for MK-8150 intervention 15: Single oral 50-mg dose of MK-8150 intervention 16: Single oral 100-mg dose of MK-8150 intervention 17: Single oral 200-mg dose of MK-8150 intervention 18: Single oral 400-mg dose of MK-8150 intervention 19: Single oral 500-mg dose of MK-8150

Protocol documents: