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

NCT01656408 | Completed Phase 1 Results

• 2 other identifiers: 8150-0022012-002596-34
• Study Type: interventional
• Target: 103
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension; Isolated Systolic Hypertension

Outcome Measures

Primary Outcomes (40)

• Number of Participants With an Adverse Event (AE)

  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. The 8 crossover Panel H participants are represented in both Panel H - MK-8150 10/20 mg column and Placebo (Panel A - J) column.

  Up to 14 days after the last dose (Up to approximately 42 days, excluding pre-dose/screening period)

• Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules

  Hemodynamic criteria for stopping drug dosing were applied (any of the following, obtained resting and if present for ≥1 hour, unless noted). For all Panels: HR \>120 bpm; SBP ≥180 mm Hg (Panels A-D/G-J) and ≥175 mm Hg (Panels E-F); DBP ≥110 mm Hg; DBP \<50 mm Hg; SBP \<90 mm Hg or participant placed in Trendelenburg position. For Panels A-H: HR increase over identified baseline of ≥25 beats per minute; SBP reduction \>30 mm Hg versus identified baseline; \>20 mm Hg drop in SBP and \>20 beats per minute rise in HR observed together versus identified baselines; \>30 mm Hg drop in orthostatic SBP and \>30 beats per minute rise in orthostatic HR observed together. For Panels I-J, any of the following-down dosing criteria if still present 24 hours after dose decrease: HR increase ≥20 beats per minute versus identified baseline; SBP reduction \>30 mm Hg versus identified baseline; SBP \<100 mm Hg; \>30 mm Hg drop in orthostatic SBP and \>30 beats per minute rise in orthostatic HR observed together.

  Up to 28 days

• Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  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. Baseline was Day 1 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline was Day 1 pre-dose value.

  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

• Change From Baseline in TWA0-24hrs cSBP in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)

  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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.

  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

• Change From Baseline in TWA0-24hrs cSBP in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F)

  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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.

  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

• Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)

  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. Baseline was Day 1 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline was Day 1 pre-dose value.

  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

• Change From Baseline in TWA0-24hrs cSBP in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)

  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. Baseline was Day 1 pre-dose value (determined separately in each period).

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline was Day 1 pre-dose value (determined separately in each period).

  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

• Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)

  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. Baseline was Day 1 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline was Day 1 pre-dose value.

  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

• Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)

  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. Baseline was Day 1 pre-dose value.

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs HR in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)

  HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 24-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. Baseline was Day 1 pre-dose value.

  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

• Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel A/B/C/D)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 and Day 10 was determined.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Maximum Observed Plasma Concentration (Cmax) of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel A/B/C/D)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 1 and Day 10 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 10 only) 48, 72 and 96 hours post dose

• Time to Maximum Observed Plasma Concentration (Tmax) of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel A/B/C/D)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 1 and Day 10 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 10 only) 48, 72 and 96 hours post dose

• Apparent Terminal Half-life (t1/2) of MK-8150 Determined Following Day 10 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel A/B/C/D)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the last dose of study drug, administered on Day 10.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• AUC0-24 of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 (Panel E/F, Day 1 Dose)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 was determined.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Cmax of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 (Panel E/F, Day 1 Dose)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 1 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• Tmax of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 (Panel E/F, Day 1 Dose)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 1 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• t1/2 of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 (Panel E/F, Day 1 Dose)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the Day 1 dose.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• AUC0-24 of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel E/F, Days 6-15)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 6 and Day 15 was determined.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Cmax of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel E/F, Days 6-15)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 6 and Day 15 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 15 only) 48, 72 and 96 hours post dose

• Tmax of MK-8150 in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel E/F, Days 6-15)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 6 and Day 15 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 15 only) 48, 72 and 96 hours post dose

• t1/2 of MK-8150 Determined Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel E/F, Days 6-15)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the last dose of study drug, administered on Day 15.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• AUC0-24 of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 and Day 28 was determined.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Cmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 1 and Day 28 was determined from the observed plasma concentration-time data.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• Tmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 1 and Day 28 was determined from the observed plasma concentration-time data.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• t1/2 of MK-8150 Determined Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the last dose of study drug, administered on Day 28.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• AUC0-24 of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 and Day 10 was determined.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Cmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 1 and Day 10 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 10 only) 48, 72 and 96 hours post dose

• Tmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 1 and Day 10 was determined from the observed plasma concentration-time data.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose, and (for Day 10 only) 48, 72 and 96 hours post dose

• t1/2 of MK-8150 Determined Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the last dose of study drug, administered on Day 10.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• AUC0-24 of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel I/J, Including Only Participants Who Completed Treatment)

  Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 and Day 28 was determined.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

• Cmax of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel I/J, Including Only Participants Who Completed Treatment)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Cmax of MK-8150 on Day 1 and Day 28 was determined from the observed plasma concentration-time data.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• Tmax of MK-8150 in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel I/J, Including Only Participants Who Completed Treatment)

  Serial plasma samples for determination of PK parameters were obtained from study participants. Tmax of MK-8150 on Day 1 and Day 28 was determined from the observed plasma concentration-time data.

  Day 1: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose; Day 28: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

• t1/2 of MK-8150 Determined Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 (Panel I/J, Including Only Participants Who Completed Treatment)

  Serial plasma samples for determination of PK parameters were obtained from study participants. t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase. t1/2 of MK-8150 was determined from plasma drug concentration data obtained following the last dose of study drug, administered on Day 28.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose

Secondary Outcomes (28)

• Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs cDBP Following Day 10 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Change From Baseline in TWA0-24hrs pSBP Following Day 10 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  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

• Change From Baseline in TWA0-24hrs pDBP Following Day 10 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel A/B/C/D)

  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

• Change From Baseline in TWA0-24hrs AIx in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)

  Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose

Study Arms (10)

Panel A: Mild/Moderate Hypertension

EXPERIMENTAL

MK-8150 or matching placebo once daily, capsules, oral, for 10 days

Drug: MK-8150; Drug: Placebo for MK-8150

Panel B: Mild/Moderate Hypertension

EXPERIMENTAL

MK-8150 or matching placebo once daily, capsules, oral, for 10 days

Drug: MK-8150; Drug: Placebo for MK-8150

Panel C: Mild/Moderate Hypertension

EXPERIMENTAL

MK-8150 or matching placebo once daily, capsules, oral, for 10 days

Drug: MK-8150; Drug: Placebo for MK-8150

Panel D: Mild/Moderate Hypertension

EXPERIMENTAL

MK-8150 or matching placebo once daily, capsules, oral, for 10 days

Drug: MK-8150; Drug: Placebo for MK-8150

Panel E-Elderly

EXPERIMENTAL

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

Drug: MK-8150; Drug: Placebo for MK-8150

Panel F - Elderly

EXPERIMENTAL

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

Drug: MK-8150; Drug: Placebo for MK-8150

Panel G - Healthy - Dose Titration

EXPERIMENTAL

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.

Drug: MK-8150; Drug: Placebo for MK-8150

Panel H - Crossover

EXPERIMENTAL

MK-8150 or matching placebo for 10 consecutive days in 2-period crossover with minimum 3 weeks washout period between the 2 treatment periods

Drug: MK-8150; Drug: Placebo for MK-8150

Panel I - Dose Titration

EXPERIMENTAL

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.

Drug: MK-8150; Drug: Placebo for MK-8150

Panel J - Dose Titration

EXPERIMENTAL

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.

Drug: MK-8150; Drug: Placebo for MK-8150

Interventions

MK-8150 DRUG

Panel A: Mild/Moderate Hypertension; Panel B: Mild/Moderate Hypertension; Panel C: Mild/Moderate Hypertension; Panel D: Mild/Moderate Hypertension; Panel E-Elderly; Panel F - Elderly; Panel G - Healthy - Dose Titration; Panel H - Crossover; Panel I - Dose Titration; Panel J - Dose Titration

Placebo for MK-8150 DRUG

Panel A: Mild/Moderate Hypertension; Panel B: Mild/Moderate Hypertension; Panel C: Mild/Moderate Hypertension; Panel D: Mild/Moderate Hypertension; Panel E-Elderly; Panel F - Elderly; Panel G - Healthy - Dose Titration; Panel H - Crossover; Panel I - Dose Titration; Panel J - Dose Titration

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hypertensive male participant between 18 to 55 years of age for Panels A to D; hypertensive male or female of non-childbearing potential between 65 to 80 years of age for Panels E and F; healthy males between 18 to 55 years of age for Panel G; hypertensive male or non-childbearing potential female between 18 to 65 years of age (inclusive) for Panel H; hypertensive male between 18 to 65 years of age for Panels I and J
• Body Mass Index (BMI) ≤ 33 kg/m\^2
• In good age appropriate health
• No history of clinically significant cardiac disease
• Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months

You may not qualify if:

• Mentally or legally incapacitated, has significant emotional problems or has a history of a clinically significant psychiatric disorder over the last 5 years
• History of stroke, chronic seizures, or a relevant major neurological disorder
• History of neoplastic disease (cancer)
• Unable to refrain from or anticipates the use of any medication, including any non-steroidal anti-inflammatory drug (NSAID) and aspirin-containing products, prescription and non-prescription drugs or herbal remedies for 2 weeks prior to study start up to end of study
• Anticipates using erectile dysfunction medications during the study
• Uses or anticipates using organic nitrates during the course of the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
• Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) 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)
• Current regular user (including recreational use) of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Knox CD, de Kam PJ, Azer K, Wong P, Ederveen AG, Shevell D, Morabito C, Meehan AG, Liu W, Reynders T, Denef JF, Mitselos A, Jonathan D, Gutstein DE, Mitra K, Sun SY, Lo MM, Cully D, Ali A. Discovery and Clinical Evaluation of MK-8150, A Novel Nitric Oxide Donor With a Unique Mechanism of Nitric Oxide Release. J Am Heart Assoc. 2016 Aug 25;5(9):e003493. doi: 10.1161/JAHA.116.003493.

  PMID: 27561272 RESULT

MeSH Terms

Conditions

Hypertension; Isolated Systolic Hypertension

Interventions

MK-8150

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Essential Hypertension

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: August 3, 2012
• Study Start: August 1, 2012
• Primary Completion: May 3, 2013
• Study Completion: May 23, 2013
• Last Updated: September 25, 2018
• Results First Posted: April 29, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share