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A Single Rising Dose Study of MK-8150 (MK-8150-001)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01590810
First received: May 1, 2012
Last updated: May 17, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Hypertension
Isolated Systolic Hypertension (ISH)
Drug: MK-8150 2.0 mg
Drug: MK-8150 10 mg
Drug: MK-8150 40 mg
Drug: MK-8150 90 mg
Drug: MK-8150 5.0 mg
Drug: MK-8150 20 mg
Drug: MK-8150 60 mg
Drug: MK-8150 120 mg
Drug: MK-8150 160 mg
Drug: MK-8150 320 mg
Drug: MK-8150 600 mg
Drug: MK-8150 900 mg
Drug: MK-8150 1200 mg
Drug: Placebo for MK-8150
Drug: MK-8150 50 mg
Drug: MK-8150 100 mg
Drug: MK-8150 200 mg
Drug: MK-8150 400 mg
Drug: MK-8150 500 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 14 days after the last dose (Up to approximately 42 days) ] [ Designated as safety issue: Yes ]
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

  • Number of Participants Who Discontinued Study Due to an AE [ Time Frame: Up to 14 days after the last dose (Up to approximately 42 days) ] [ Designated as safety issue: Yes ]
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

  • Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose; except Period 1: Pre-dose and 2, 4, 12 and 24 hours post dose ] [ Designated as safety issue: No ]
    AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

  • Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

  • Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

  • Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

  • Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose ] [ Designated as safety issue: No ]
    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose ] [ Designated as safety issue: No ]
    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose ] [ Designated as safety issue: No ]
    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose ] [ Designated as safety issue: No ]
    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

  • Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose ] [ Designated as safety issue: No ]
    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.


Enrollment: 34
Study Start Date: May 2012
Study Completion Date: February 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A-Healthy
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.
Drug: MK-8150 2.0 mg
Single oral 2.0-mg dose of MK-8150
Drug: MK-8150 10 mg
Single oral 10-mg dose of MK-8150
Drug: MK-8150 40 mg
Single oral 40-mg dose of MK-8150 without food (fasted) and with food (fed)
Drug: MK-8150 90 mg
Single oral 90-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel B-Healthy
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.
Drug: MK-8150 5.0 mg
Single oral 5.0-mg dose of MK-8150
Drug: MK-8150 20 mg
Single oral 20-mg dose of MK-8150
Drug: MK-8150 60 mg
Single oral 60-mg dose of MK-8150
Drug: MK-8150 120 mg
Single oral 120-mg dose of MK-8150
Drug: MK-8150 160 mg
Single oral 160-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel C-Mild/Moderate Hypertension
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.
Drug: MK-8150 160 mg
Single oral 160-mg dose of MK-8150
Drug: MK-8150 320 mg
Single oral 320-mg dose of MK-8150
Drug: MK-8150 600 mg
Single oral 600-mg dose of MK-8150
Drug: MK-8150 900 mg
Single oral 900-mg dose of MK-8150
Drug: MK-8150 1200 mg
Single oral 1200-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel D-Healthy
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.
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Drug: MK-8150 50 mg
Single oral 50-mg dose of MK-8150
Drug: MK-8150 100 mg
Single oral 100-mg dose of MK-8150
Drug: MK-8150 200 mg
Single oral 200-mg dose of MK-8150
Drug: MK-8150 400 mg
Single oral 400-mg dose of MK-8150
Drug: MK-8150 500 mg
Single oral 500-mg dose of MK-8150

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Between 18 and 50 years of age for Panels A, B and D, or between 18 and 60 years of age (inclusive) for Panel C.
  • Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A, B, and D or SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication
  • Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2
  • Healthy (with the exception of hypertensive subjects in Panel C)
  • No clinically significant abnormality on electrocardiogram (ECG)
  • No history of clinically significant cardiac disease
  • No history of heart failure
  • Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months

Exclusion Criteria:

  • Mentally or legally incapacitated
  • History of stroke, chronic seizures, or major neurological disorder
  • History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Functional disability that can interfere with rising from a sitting position to the standing position
  • History of neoplastic disease (cancer)
  • Unable to refrain from or anticipates the use of any medication during the study
  • Anticipates using medication for erectile dysfunction during the study
  • Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
  • Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study
  • Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day
  • Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day
  • Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
  • History of significant multiple and/or severe allergies (including latex allergy)
  • Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590810

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01590810     History of Changes
Other Study ID Numbers: 8150-001  2012-001281-15 
Study First Received: May 1, 2012
Results First Received: March 3, 2016
Last Updated: May 17, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2016