Hypertension, Isolated Systolic Hypertension
Conditions
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.
Interventions
DRUGMK-8150
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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 last dose of study drug, administered on Day 28. |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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). |
| 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) | 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 | 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). |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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 last dose of study drug, administered on Day 10. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose | Serial plasma samples for determination of PK parameters were obtained from study participants. AUC0-24 of MK-8150 on Day 1 was determined. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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. |
| 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) | 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 | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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 last dose of study drug, administered on Day 15. |
| AUC0-24 of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | 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 | 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. |
| Cmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | 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 | 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. |
| Tmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | 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 | 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. |
| t1/2 of MK-8150 Determined Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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 last dose of study drug, administered on Day 28. |
| AUC0-24 of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| Cmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | 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 | 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. |
| Tmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | 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 | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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 last dose of study drug, administered on Day 10. |
| 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) | 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 | 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. |
| 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) | 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 | 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. |
| Number of Participants With an Adverse Event (AE) | Up to 14 days after the last dose (Up to approximately 42 days, excluding pre-dose/screening period) | 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. |
| Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | Up to 28 days | 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. |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| 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) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| 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) | 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 | 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. |
| Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. |
| Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | 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 | 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. |
| 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) | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. Baseline was Day 1 pre-dose value. |
| 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 | 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. Baseline was Day 1 pre-dose value. |
| 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 | 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. Baseline was Day 1 pre-dose value. |
| 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose 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 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose 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 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| 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 F) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | 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 | 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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value. |
| Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | 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 | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | 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 | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value (determined separately in each period). |
| Change From Baseline in TWA0-24hrs cDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value (determined separately in each period). |
| Change From Baseline in TWA0-24hrs pSBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | 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 | 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. Baseline was Day 1 pre-dose value (determined separately in each period). |
| Change From Baseline in TWA0-24hrs pDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | 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 | 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. Baseline was Day 1 pre-dose value (determined separately in each period). |
| Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | 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 | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | 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 | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | 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 | 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. Baseline was Day 1 pre-dose value. |
| Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | 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 | 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. Baseline was Day 1 pre-dose value. |
| 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 | 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. Baseline was Day 1 pre-dose value. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Panel A - Participants With Mild to Moderate Hypertension 6 participants were randomly assigned to receive MK-8150 5 mg once daily and 2 participants were randomly assigned to receive placebo once daily for 10 days | 8 |
| Panel B - Participants With Mild to Moderate Hypertension 6 participants were randomly assigned to receive MK-8150 10 mg once daily and 2 participants were randomly assigned to receive placebo once daily for 10 days | 8 |
| Panel C - Participants With Mild to Moderate Hypertension 6 participants were randomly assigned to receive MK-8150 20 mg once daily and 2 participants were randomly assigned to receive placebo once daily for 10 days | 8 |
| Panel D - Participants With Mild to Moderate Hypertension 5 participants were randomly assigned to receive MK-8150 15 mg once daily and 2 participants were randomly assigned to receive placebo once daily for 10 days | 7 |
| Panel E - Elderly Participants With Mild/Moderate Hypertension 6 participants were randomly assigned to receive a single dose of MK-8150 3 mg on Day 1 and to also receive MK-8150 2 mg once daily on Days 6-15 (10 days of multiple dose administration); 3 participants were randomly assigned to receive placebo (single dose) on Day 1 and once daily on Days 6-15 | 9 |
| Panel F - Elderly Participants With Mild/Moderate Hypertension 6 participants were randomly assigned to receive a single dose of MK-8150 6 mg on Day 1 and to also receive MK-8150 4 mg once daily on Days 6-15 (10 days of multiple dose administration); 3 participants were randomly assigned to receive placebo (single dose) on Day 1 and once daily on Days 6-15 | 9 |
| Panel G - Healthy Participants 8 participants were randomly assigned to receive MK-8150 once daily as follows: 20 mg (Days 1-7), 30 mg (Days 8-14), 40 mg (Days 15-21), 60 mg (Days 22-28); 2 participants were randomly assigned to receive placebo once daily on Days 1-28. Dose administered could be increased or decreased based on defined criteria | 10 |
| Panel H - Participants With Resistant Hypertension In Panel with crossover design, 4 participants were randomly assigned to receive active drug (MK-8150) in Period 1 and placebo in Period 2 and 4 participants were randomly assigned to receive placebo in Period 1 and active drug in Period 2. Active drug regimen was MK-8150 once daily as follows: 10 mg (Days 1-2), 20 mg (Days 3-10); placebo regimen was placebo once daily on Days 1-10 | 8 |
| Panel I - Participants With Mild to Moderate Hypertension 12 participants were randomly assigned to receive MK-8150 once daily as follows: 5 mg (Days 1-7), 10 mg (Days 8-14), 20 mg (Days 15-21), 40 mg (Days 22-28); 6 participants were randomly assigned to receive placebo once daily on Days 1-28. Dose administered could be increased or decreased based on defined criteria | 18 |
| Panel J - Participants With Mild to Moderate Hypertension 12 participants were randomly assigned to receive MK-8150 once daily as follows: 10 mg (Days 1-7), 20 mg (Days 8-28); 6 participants were randomly assigned to receive placebo once daily on Days 1-28. Dose administered could be increased or decreased based on defined criteria | 18 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Panel A - Participants With Mild to Moderate Hypertension | Panel B - Participants With Mild to Moderate Hypertension | Panel C - Participants With Mild to Moderate Hypertension | Panel D - Participants With Mild to Moderate Hypertension | Panel E - Elderly Participants With Mild/Moderate Hypertension | Panel F - Elderly Participants With Mild/Moderate Hypertension | Panel G - Healthy Participants | Panel H - Participants With Resistant Hypertension | Panel I - Participants With Mild to Moderate Hypertension | Panel J - Participants With Mild to Moderate Hypertension |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 13.2 | 46.1 years STANDARD_DEVIATION 6.3 | 41.3 years STANDARD_DEVIATION 10.8 | 42.0 years STANDARD_DEVIATION 11.4 | 42.7 years STANDARD_DEVIATION 10.8 | 72.6 years STANDARD_DEVIATION 4.2 | 69.9 years STANDARD_DEVIATION 2.5 | 41.5 years STANDARD_DEVIATION 11.2 | 58.1 years STANDARD_DEVIATION 5.6 | 51.5 years STANDARD_DEVIATION 8.5 | 54.8 years STANDARD_DEVIATION 9.6 |
| Augmentation Index (AIx) | 19 percent STANDARD_DEVIATION 13 | 23 percent STANDARD_DEVIATION 8 | 13 percent STANDARD_DEVIATION 12 | 11 percent STANDARD_DEVIATION 18 | 10 percent STANDARD_DEVIATION 12 | 31 percent STANDARD_DEVIATION 7 | 30 percent STANDARD_DEVIATION 6 | 5 percent STANDARD_DEVIATION 15 | 20 percent STANDARD_DEVIATION 11 | 19 percent STANDARD_DEVIATION 9 | 23 percent STANDARD_DEVIATION 7 |
| Central Diastolic Blood Pressure (cDBP) | 87 mm Hg STANDARD_DEVIATION 10 | 93 mm Hg STANDARD_DEVIATION 5 | 87 mm Hg STANDARD_DEVIATION 8 | 87 mm Hg STANDARD_DEVIATION 10 | 87 mm Hg STANDARD_DEVIATION 7 | 84 mm Hg STANDARD_DEVIATION 7 | 86 mm Hg STANDARD_DEVIATION 11 | 73 mm Hg STANDARD_DEVIATION 9 | 85 mm Hg STANDARD_DEVIATION 8 | 89 mm Hg STANDARD_DEVIATION 6 | 90 mm Hg STANDARD_DEVIATION 11 |
| Central Systolic Blood Pressure (cSBP) | 131 mm Hg STANDARD_DEVIATION 16 | 141 mm Hg STANDARD_DEVIATION 15 | 126 mm Hg STANDARD_DEVIATION 10 | 127 mm Hg STANDARD_DEVIATION 16 | 126 mm Hg STANDARD_DEVIATION 7 | 143 mm Hg STANDARD_DEVIATION 11 | 144 mm Hg STANDARD_DEVIATION 11 | 103 mm Hg STANDARD_DEVIATION 11 | 130 mm Hg STANDARD_DEVIATION 12 | 133 mm Hg STANDARD_DEVIATION 10 | 136 mm Hg STANDARD_DEVIATION 12 |
| Heart Rate (HR) | 63 beats per minute STANDARD_DEVIATION 10 | 65 beats per minute STANDARD_DEVIATION 14 | 63 beats per minute STANDARD_DEVIATION 7 | 66 beats per minute STANDARD_DEVIATION 12 | 61 beats per minute STANDARD_DEVIATION 10 | 59 beats per minute STANDARD_DEVIATION 11 | 68 beats per minute STANDARD_DEVIATION 9 | 54 beats per minute STANDARD_DEVIATION 7 | 63 beats per minute STANDARD_DEVIATION 9 | 62 beats per minute STANDARD_DEVIATION 10 | 66 beats per minute STANDARD_DEVIATION 9 |
| Peripheral Diastolic Blood Pressure (pDBP) | 86 mm Hg STANDARD_DEVIATION 10 | 92 mm Hg STANDARD_DEVIATION 6 | 86 mm Hg STANDARD_DEVIATION 9 | 90 mm Hg STANDARD_DEVIATION 10 | 86 mm Hg STANDARD_DEVIATION 7 | 82 mm Hg STANDARD_DEVIATION 5 | 86 mm Hg STANDARD_DEVIATION 11 | 72 mm Hg STANDARD_DEVIATION 9 | 84 mm Hg STANDARD_DEVIATION 8 | 89 mm Hg STANDARD_DEVIATION 6 | 90 mm Hg STANDARD_DEVIATION 10 |
| Peripheral Systolic Blood Pressure (pSBP) | 142 mm Hg STANDARD_DEVIATION 13 | 150 mm Hg STANDARD_DEVIATION 12 | 137 mm Hg STANDARD_DEVIATION 7 | 142 mm Hg STANDARD_DEVIATION 17 | 139 mm Hg STANDARD_DEVIATION 5 | 147 mm Hg STANDARD_DEVIATION 10 | 151 mm Hg STANDARD_DEVIATION 9 | 117 mm Hg STANDARD_DEVIATION 7 | 141 mm Hg STANDARD_DEVIATION 11 | 145 mm Hg STANDARD_DEVIATION 9 | 147 mm Hg STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 91 Participants | 8 Participants | 8 Participants | 8 Participants | 7 Participants | 5 Participants | 4 Participants | 10 Participants | 5 Participants | 18 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 5 / 6 | 6 / 6 | 3 / 5 | 4 / 6 | 3 / 6 | 7 / 8 | 6 / 8 | 12 / 12 | 10 / 12 | 23 / 36 | 1 / 103 | 11 / 103 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 | 0 / 36 | 0 / 103 | 0 / 103 |
Outcome results
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 70.7 hr | Geometric Coefficient of Variation 41 |
| Panel B - MK-8150 10 mg | 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) | 78.6 hr | Geometric Coefficient of Variation 19 |
| Panel C - MK-8150 20 mg | 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) | 46.7 hr | Geometric Coefficient of Variation 74 |
| Panel D - MK-8150 15 mg | 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) | 58.0 hr | Geometric Coefficient of Variation 45 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 1.84 μM*hr | Geometric Coefficient of Variation 13 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 6.76 μM*hr | Geometric Coefficient of Variation 36 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 12.3 μM*hr | Geometric Coefficient of Variation 30 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 3.22 μM*hr | Geometric Coefficient of Variation 21 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 6.97 μM*hr | Geometric Coefficient of Variation 19 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 19.2 μM*hr | Geometric Coefficient of Variation 23 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 5.16 μM*hr | Geometric Coefficient of Variation 18 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 16.1 μM*hr | Geometric Coefficient of Variation 34 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 6) | 1.08 μM*hr | Geometric Coefficient of Variation 16 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 4) | 2.98 μM*hr | Geometric Coefficient of Variation 22 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 6) | 2.23 μM*hr | Geometric Coefficient of Variation 16 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 4) | 6.58 μM*hr | Geometric Coefficient of Variation 26 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 1.17 μM*hr | Geometric Coefficient of Variation 14 |
| Panel B - MK-8150 10 mg | 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) | 2.37 μM*hr | Geometric Coefficient of Variation 14 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | AUC0-24 of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 1 (N = 8) | 8.08 μM*hr | Geometric Coefficient of Variation 23 |
| Panel A - MK-8150 5 mg | AUC0-24 of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 28 (N = 7) | 65.5 μM*hr | Geometric Coefficient of Variation 30 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | AUC0-24 of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 1 (N = 8) | 3.56 μM*hr | Geometric Coefficient of Variation 20 |
| Panel A - MK-8150 5 mg | AUC0-24 of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 10 (N = 6) | 25.1 μM*hr | Geometric Coefficient of Variation 31 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and completed the 28 days of treatment, and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 10, 9) | 1.80 μM*hr | Geometric Coefficient of Variation 19 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 10, 9) | 39.1 μM*hr | Geometric Coefficient of Variation 31 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 10, 9) | 3.80 μM*hr | Geometric Coefficient of Variation 16 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 10, 9) | 28.5 μM*hr | Geometric Coefficient of Variation 40 |
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -5.3 mm Hg | Standard Error 2.6 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -6.2 mm Hg | Standard Error 3.4 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -15.3 mm Hg | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -13.9 mm Hg | Standard Error 1 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -19.5 mm Hg | Standard Error 2.4 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -18.4 mm Hg | Standard Error 1.9 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -12.1 mm Hg | Standard Error 3.7 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -12.8 mm Hg | Standard Error 2.3 |
| Panel E - MK-8150 3/2 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -5.4 mm Hg | Standard Error 2.3 |
| Panel E - MK-8150 3/2 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -9.7 mm Hg | Standard Error 3 |
Comparison: Day 1p-value: 0.97890% CI: [-6.4, 6.6]Mixed Models Analysis
Comparison: Day 1p-value: 0.00590% CI: [-15.4, -4.5]Mixed Models Analysis
Comparison: Day 1p-value: 090% CI: [-19.8, -8.4]Mixed Models Analysis
Comparison: Day 1p-value: 0.0390% CI: [-13, -1.9]Mixed Models Analysis
Comparison: Day 10p-value: 0.48490% CI: [-4.9, 11.9]Mixed Models Analysis
Comparison: Day 10p-value: 0.16990% CI: [-9.3, 0.9]Mixed Models Analysis
Comparison: Day 10p-value: 0.02390% CI: [-14.9, -2.6]Mixed Models Analysis
Comparison: Day 10p-value: 0.60590% CI: [-10.4, 5.5]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 3) | -16.3 mm Hg | Standard Error 3.3 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 3) | -11.8 mm Hg | Standard Error 3.6 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 3) | -10.6 mm Hg | Standard Error 3.9 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 3) | -15.5 mm Hg | Standard Error 3.2 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 3) | -15.5 mm Hg | Standard Error 7.3 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 3) | -16.9 mm Hg | Standard Error 5.9 |
Comparison: Day 1p-value: 0.85590% CI: [-9, 7.3]Mixed Models Analysis
Comparison: Day 6p-value: 0.65890% CI: [-10.8, 18.1]Mixed Models Analysis
Comparison: Day 15p-value: 0.39290% CI: [-6.3, 18.9]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 3) | -16.1 mm Hg | Standard Error 3.6 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 6, 3) | -17.2 mm Hg | Standard Error 3.9 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 4, 3) | -20.8 mm Hg | Standard Error 3.6 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 3) | -20.5 mm Hg | Standard Error 3.1 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 6, 3) | -24.6 mm Hg | Standard Error 2.7 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 4, 3) | -23.8 mm Hg | Standard Error 3.6 |
Comparison: Day 1p-value: 0.35790% CI: [-3.9, 12.8]Mixed Models Analysis
Comparison: Day 6p-value: 0.1590% CI: [-1.2, 15.9]Mixed Models Analysis
Comparison: Day 15p-value: 0.57890% CI: [-6.3, 12.3]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | -8.3 mm Hg | Standard Error 2.2 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | -8.0 mm Hg | Standard Error 1.7 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | 2.8 mm Hg | Standard Error 3.3 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | -2.3 mm Hg | Standard Error 1 |
Comparison: Day 1p-value: 0.02590% CI: [-18, -3.6]Mixed Models Analysis
Comparison: Day 28p-value: 0.05590% CI: [-11, -1.1]Mixed Models Analysis
Primary
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).
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 7, 8) | -10.1 mm Hg | Standard Error 1.8 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 6, 8) | -7.7 mm Hg | Standard Error 2.2 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 7, 8) | -4.5 mm Hg | Standard Error 1.8 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 6, 8) | -1.8 mm Hg | Standard Error 1 |
Comparison: Day 1p-value: 0.09990% CI: [-11.1, 0]Mixed Models Analysis
Comparison: Day 10p-value: 0.03490% CI: [-10.1, -1.7]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 12, 6) | -11.2 mm Hg | Standard Error 1.6 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 10, 6) | -15.2 mm Hg | Standard Error 2.3 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 12, 6) | -7.4 mm Hg | Standard Error 2.9 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 10, 6) | -14.4 mm Hg | Standard Error 2.6 |
Comparison: Day 1p-value: 0.27990% CI: [-9.7, 2.1]Mixed Models Analysis
Comparison: Day 28p-value: 0.81790% CI: [-6.9, 5.2]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 12, 6) | -16.7 mm Hg | Standard Error 2.4 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 9, 6) | -11.5 mm Hg | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 12, 6) | -5.4 mm Hg | Standard Error 1.6 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 9, 6) | -5.4 mm Hg | Standard Error 2.4 |
Comparison: Day 1p-value: 0.00390% CI: [-16.8, -5.9]Mixed Models Analysis
Comparison: Day 28p-value: 0.10590% CI: [-12.3, 0.1]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 3) | 2.5 beats per minute | Standard Error 1.3 |
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 3) | 0.5 beats per minute | Standard Error 1.2 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 3) | 1.6 beats per minute | Standard Error 0.8 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 3) | 2.0 beats per minute | Standard Error 2.2 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 3) | 0.8 beats per minute | Standard Error 0.3 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 3) | 0.7 beats per minute | Standard Error 1.3 |
Comparison: Day 1p-value: 0.56390% CI: [-6, 3]Mixed Models Analysis
Comparison: Day 6p-value: 0.38190% CI: [-0.8, 2.5]Mixed Models Analysis
Comparison: Day 15p-value: 0.38790% CI: [-1.7, 5.2]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 3) | -1.2 beats per minute | Standard Error 1.7 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 6, 3) | -0.2 beats per minute | Standard Error 1.7 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 4, 3) | -1.6 beats per minute | Standard Error 1.5 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 3) | -1.5 beats per minute | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 6, 3) | -2.1 beats per minute | Standard Error 3.3 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 4, 3) | -5.8 beats per minute | Standard Error 1.1 |
Comparison: Day 1p-value: 0.94290% CI: [-5.1, 5.5]Mixed Models Analysis
Comparison: Day 6p-value: 0.62790% CI: [-4.8, 8.5]Mixed Models Analysis
Comparison: Day 15p-value: 0.04690% CI: [0.9, 7.6]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | 1.8 beats per minute | Standard Error 2 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | -1.1 beats per minute | Standard Error 1.4 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 8 (N = 8, 2) | 0.5 beats per minute | Standard Error 2.1 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 22 (N = 7, 2) | 0.8 beats per minute | Standard Error 1.6 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 15 (N = 7, 2) | 2.3 beats per minute | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 22 (N = 7, 2) | 1.1 beats per minute | Standard Error 1.6 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 15 (N = 7, 2) | 0.2 beats per minute | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | 0.5 beats per minute | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 8 (N = 8, 2) | 0.8 beats per minute | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | -1.1 beats per minute | Standard Error 1.4 |
Comparison: Day 1p-value: 0.99990% CI: [-4.4, 4.4]Mixed Models Analysis
Comparison: Day 8p-value: 0.93490% CI: [-5.7, 5.2]Mixed Models Analysis
Comparison: Day 15p-value: 0.54790% CI: [-3.7, 7.9]Mixed Models Analysis
Comparison: Day 22p-value: 0.90690% CI: [-5.2, 4.5]Mixed Models Analysis
Comparison: Day 28p-value: 0.68290% CI: [-4, 6.6]Mixed Models Analysis
Primary
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).
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 7, 8) | -2.4 beats per minute | Standard Error 1.3 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 6, 8) | -0.6 beats per minute | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 7, 8) | 0.0 beats per minute | Standard Error 2.3 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 6, 8) | -2.0 beats per minute | Standard Error 1.5 |
Comparison: Day 1p-value: 0.28190% CI: [-6.5, 1.6]Mixed Models Analysis
Comparison: Day 10p-value: 0.33390% CI: [-1.2, 4]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | 0.0 beats per minute | Standard Error 3.7 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -3.6 beats per minute | Standard Error 1.3 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -7.2 beats per minute | Standard Error 2.5 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -5.5 beats per minute | Standard Error 2 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -12.3 beats per minute | Standard Error 2.4 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -10.5 beats per minute | Standard Error 1.6 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -1.0 beats per minute | Standard Error 2.4 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -4.0 beats per minute | Standard Error 3.2 |
| Panel E - MK-8150 3/2 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -1.9 beats per minute | Standard Error 1.3 |
| Panel E - MK-8150 3/2 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -2.1 beats per minute | Standard Error 2 |
Comparison: Day 1p-value: 0.63590% CI: [-4.9, 8.7]Mixed Models Analysis
Comparison: Day 1p-value: 0.07790% CI: [-10.1, -0.4]Mixed Models Analysis
Comparison: Day 1p-value: 0.00190% CI: [-15, -5.7]Mixed Models Analysis
Comparison: Day 1p-value: 0.55690% CI: [-8, 3.9]Mixed Models Analysis
Comparison: Day 10p-value: 0.52790% CI: [-5.5, 2.5]Mixed Models Analysis
Comparison: Day 10p-value: 0.23490% CI: [-8.1, 1.4]Mixed Models Analysis
Comparison: Day 10p-value: 0.00290% CI: [-12.7, -4.1]Mixed Models Analysis
Comparison: Day 10p-value: 0.72690% CI: [-4.2, 6.5]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 8 (N = 12, 6) | 1.2 beats per minute | Standard Error 1.9 |
| Panel A - MK-8150 5 mg | 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) | Day 22 (N = 10, 6) | 0.1 beats per minute | Standard Error 2 |
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 12, 6) | 0.3 beats per minute | Standard Error 1.9 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 10, 6) | 0.7 beats per minute | Standard Error 2.7 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 10, 6) | 0.8 beats per minute | Standard Error 2.3 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 10, 6) | -4.4 beats per minute | Standard Error 1.3 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 12, 6) | -0.5 beats per minute | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | 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) | Day 8 (N = 12, 6) | -2.8 beats per minute | Standard Error 2 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 10, 6) | -1.6 beats per minute | Standard Error 1.8 |
| Panel B - MK-8150 10 mg | 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) | Day 22 (N = 10, 6) | -2.9 beats per minute | Standard Error 1.4 |
Comparison: Day 1p-value: 0.75690% CI: [-3.2, 4.7]Mixed Models Analysis
Comparison: Day 8p-value: 0.15890% CI: [-0.7, 8.6]Mixed Models Analysis
Comparison: Day 15p-value: 0.40490% CI: [-2.4, 7.1]Mixed Models Analysis
Comparison: Day 22p-value: 0.21490% CI: [-1, 7.1]Mixed Models Analysis
Comparison: Day 28p-value: 0.08690% CI: [0.2, 10]Mixed Models Analysis
Primary
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.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 12, 6) | -3.0 beats per minute | Standard Error 1.1 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 10, 6) | -1.2 beats per minute | Standard Error 1.6 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 9, 6) | -0.3 beats per minute | Standard Error 1.7 |
| Panel A - MK-8150 5 mg | 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) | Day 22 (N = 9, 6) | -1.0 beats per minute | Standard Error 1.5 |
| Panel A - MK-8150 5 mg | 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) | Day 8 (N = 11, 6) | -0.6 beats per minute | Standard Error 1.5 |
| Panel B - MK-8150 10 mg | 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) | Day 22 (N = 9, 6) | 2.0 beats per minute | Standard Error 4.5 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 9, 6) | -2.8 beats per minute | Standard Error 3.6 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 12, 6) | -1.6 beats per minute | Standard Error 3.4 |
| Panel B - MK-8150 10 mg | 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) | Day 8 (N = 11, 6) | -2.8 beats per minute | Standard Error 3.6 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 10, 6) | -2.6 beats per minute | Standard Error 3 |
Comparison: Day 1p-value: 0.69190% CI: [-7.5, 4.6]Mixed Models Analysis
Comparison: Day 8p-value: 0.5790% CI: [-4.3, 8.8]Mixed Models Analysis
Comparison: Day 15p-value: 0.66690% CI: [-4.2, 7.1]Mixed Models Analysis
Comparison: Day 22p-value: 0.53490% CI: [-10.9, 4.9]Mixed Models Analysis
Comparison: Day 28p-value: 0.52890% CI: [-4.1, 9.2]Mixed Models Analysis
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 4) | 0.192 μM | Geometric Coefficient of Variation 16 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 6) | 0.109 μM | Geometric Coefficient of Variation 19 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 6) | 0.208 μM | Geometric Coefficient of Variation 10 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 4) | 0.425 μM | Geometric Coefficient of Variation 25 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 0.129 μM | Geometric Coefficient of Variation 25 |
| Panel B - MK-8150 10 mg | 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) | 0.268 μM | Geometric Coefficient of Variation 17 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Cmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 1 (N = 8) | 0.664 μM | Geometric Coefficient of Variation 8.5 |
| Panel A - MK-8150 5 mg | Cmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 28 (N = 7) | 4.05 μM | Geometric Coefficient of Variation 22 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Cmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 1 (N = 8) | 0.395 μM | Geometric Coefficient of Variation 27 |
| Panel A - MK-8150 5 mg | Cmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 10 (N = 6) | 1.71 μM | Geometric Coefficient of Variation 31 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and completed the 28 days of treatment, and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 10, 9) | 2.72 μM | Geometric Coefficient of Variation 29 |
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 10, 9) | 0.213 μM | Geometric Coefficient of Variation 28 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 10, 9) | 0.395 μM | Geometric Coefficient of Variation 18 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 10, 9) | 1.75 μM | Geometric Coefficient of Variation 34 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 0.183 μM | Geometric Coefficient of Variation 7.7 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 0.440 μM | Geometric Coefficient of Variation 20 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 0.784 μM | Geometric Coefficient of Variation 26 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 0.353 μM | Geometric Coefficient of Variation 18 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 0.656 μM | Geometric Coefficient of Variation 12 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 1.25 μM | Geometric Coefficient of Variation 16 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 0.502 μM | Geometric Coefficient of Variation 32 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 1.14 μM | Geometric Coefficient of Variation 35 |
Primary
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.
Time frame: Up to 28 days
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A - MK-8150 5 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 3 participants |
| Panel B - MK-8150 10 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 0 participants |
| Panel C - MK-8150 20 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 1 participants |
| Panel D - MK-8150 15 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 0 participants |
| Panel E - MK-8150 3/2 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 2 participants |
| Panel F - MK-8150 6/4 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 1 participants |
| Panel G - MK-8150 20/30/40/60 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 0 participants |
| Panel H - MK-8150 10/20 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 1 participants |
| Panel I - MK-8150 5/10/20/40 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 1 participants |
| Panel J - MK-8150 10/20 mg | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 3 participants |
| Placebo (Panel A - J) | Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules | 0 participants |
Primary
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.
Time frame: Up to 14 days after the last dose (Up to approximately 42 days, excluding pre-dose/screening period)
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A - MK-8150 5 mg | Number of Participants With an Adverse Event (AE) | 4 participants |
| Panel B - MK-8150 10 mg | Number of Participants With an Adverse Event (AE) | 5 participants |
| Panel C - MK-8150 20 mg | Number of Participants With an Adverse Event (AE) | 6 participants |
| Panel D - MK-8150 15 mg | Number of Participants With an Adverse Event (AE) | 3 participants |
| Panel E - MK-8150 3/2 mg | Number of Participants With an Adverse Event (AE) | 4 participants |
| Panel F - MK-8150 6/4 mg | Number of Participants With an Adverse Event (AE) | 3 participants |
| Panel G - MK-8150 20/30/40/60 mg | Number of Participants With an Adverse Event (AE) | 7 participants |
| Panel H - MK-8150 10/20 mg | Number of Participants With an Adverse Event (AE) | 6 participants |
| Panel I - MK-8150 5/10/20/40 mg | Number of Participants With an Adverse Event (AE) | 12 participants |
| Panel J - MK-8150 10/20 mg | Number of Participants With an Adverse Event (AE) | 10 participants |
| Placebo (Panel A - J) | Number of Participants With an Adverse Event (AE) | 24 participants |
| Post Study | Number of Participants With an Adverse Event (AE) | 1 participants |
| Screening | Number of Participants With an Adverse Event (AE) | 12 participants |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 69.6 hr | Geometric Coefficient of Variation 44 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 68.1 hr | Geometric Coefficient of Variation 36 |
| Panel B - MK-8150 10 mg | 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) | 92.6 hr | Geometric Coefficient of Variation 63 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | t1/2 of MK-8150 Determined Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | 51.8 hr | Geometric Coefficient of Variation 48 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and completed the 28 days of treatment, and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 73.9 hr | Geometric Coefficient of Variation 37 |
| Panel B - MK-8150 10 mg | 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) | 81.0 hr | Geometric Coefficient of Variation 18 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 85.0 hr | Geometric Coefficient of Variation 35 |
| Panel B - MK-8150 10 mg | 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) | 82.1 hr | Geometric Coefficient of Variation 53 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 1 hr | Full Range 2.6 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 1 hr | Full Range 3.4 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 0.75 hr | Full Range 1 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 1 hr | Full Range 2.4 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 1.25 hr | Full Range 2.4 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 1.25 hr | Full Range 1.9 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5) | 1 hr | Full Range 2.3 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5) | 0.5 hr | Full Range 3.7 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 6) | 1 hr | Full Range 2.6 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 4) | 1 hr | — |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 6) | 1 hr | Full Range 2.4 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 4) | 1 hr | — |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | 1 hr | Full Range 2.6 |
| Panel B - MK-8150 10 mg | 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) | 1 hr | Full Range 2.4 |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Tmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 1 (N = 8) | 1.0 hr | Full Range 2.6 |
| Panel A - MK-8150 5 mg | Tmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) | Day 28 (N = 7) | 1.5 hr | — |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Tmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 1 (N = 8) | 1.0 hr | Full Range 2.6 |
| Panel A - MK-8150 5 mg | Tmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) | Day 10 (N = 6) | 1.0 hr | — |
Primary
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.
Time frame: 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
Population: All participants who met protocol entry criteria, received study drug and completed the 28 days of treatment, and had data available for the measure
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 10, 9) | 0.75 hr | Full Range 2.6 |
| Panel A - MK-8150 5 mg | 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) | Day 28 (N = 10, 9) | 0.5 hr | — |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 10, 9) | 1.0 hr | Full Range 2.4 |
| Panel B - MK-8150 10 mg | 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) | Day 28 (N = 10, 9) | 1 hr | — |
Secondary
Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Day 1 (N = 12, 6) | -10.4 percentage of central pulse pressure | Standard Error 1.8 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Day 28 (N = 9, 6) | -9.9 percentage of central pulse pressure | Standard Error 2.1 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Day 1 (N = 12, 6) | -5.9 percentage of central pulse pressure | Standard Error 1 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | Day 28 (N = 9, 6) | -6.1 percentage of central pulse pressure | Standard Error 1 |
Comparison: Day 1p-value: 0.06190% CI: [-8.4, -0.6]Mixed Models Analysis
Comparison: Day 28p-value: 0.16190% CI: [-8.3, 0.7]Mixed Models Analysis
Secondary
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)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 3) | -3.8 percentage of central pulse pressure | Standard Error 2.7 |
| Panel A - MK-8150 5 mg | 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) | Day 6 (N = 5, 3) | -5.2 percentage of central pulse pressure | Standard Error 3.6 |
| Panel A - MK-8150 5 mg | 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) | Day 15 (N = 5, 3) | -3.5 percentage of central pulse pressure | Standard Error 2.6 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 3) | -2.6 percentage of central pulse pressure | Standard Error 0.9 |
| Panel B - MK-8150 10 mg | 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) | Day 6 (N = 5, 3) | -1.0 percentage of central pulse pressure | Standard Error 0.8 |
| Panel B - MK-8150 10 mg | 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) | Day 15 (N = 5, 3) | 0.3 percentage of central pulse pressure | Standard Error 1.2 |
Comparison: Day 1p-value: 0.71590% CI: [-7.4, 4.8]Mixed Models Analysis
Comparison: Day 6p-value: 0.33890% CI: [-11.9, 3.4]Mixed Models Analysis
Comparison: Day 15p-value: 0.28190% CI: [-10, 2.3]Mixed Models Analysis
Secondary
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 F)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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 F) | Day 1 (N = 6, 3) | -4.8 percentage of central pulse pressure | Standard Error 2.3 |
| Panel A - MK-8150 5 mg | 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 F) | Day 6 (N = 6, 3) | -5.1 percentage of central pulse pressure | Standard Error 1.5 |
| Panel A - MK-8150 5 mg | 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 F) | Day 15 (N = 4, 3) | -6.8 percentage of central pulse pressure | Standard Error 2.1 |
| Panel B - MK-8150 10 mg | 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 F) | Day 1 (N = 6, 3) | -2.5 percentage of central pulse pressure | Standard Error 2.1 |
| Panel B - MK-8150 10 mg | 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 F) | Day 6 (N = 6, 3) | 0.5 percentage of central pulse pressure | Standard Error 2.6 |
| Panel B - MK-8150 10 mg | 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 F) | Day 15 (N = 4, 3) | 0.9 percentage of central pulse pressure | Standard Error 2.2 |
Comparison: Day 1p-value: 0.47790% CI: [-7.9, 3.3]Mixed Models Analysis
Comparison: Day 6p-value: 0.0990% CI: [-11, -0.2]Mixed Models Analysis
Comparison: Day 15p-value: 0.02890% CI: [-13, -2.2]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | -11.8 percentage of central pulse pressure | Standard Error 2.1 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | -14.2 percentage of central pulse pressure | Standard Error 2.1 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 1 (N = 8, 2) | -1.3 percentage of central pulse pressure | Standard Error 3.8 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | Day 28 (N = 7, 2) | -1.4 percentage of central pulse pressure | Standard Error 0.5 |
Comparison: Day 1p-value: 0.04690% CI: [-18.8, -2.3]Mixed Models Analysis
Comparison: Day 28p-value: 0.00190% CI: [-17.2, -8.6]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)
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. Baseline was Day 1 pre-dose value (determined separately in each period).
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Day 1 (N = 7, 8) | -3.9 percentage of central pulse pressure | Standard Error 0.9 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Day 10 (N = 6, 8) | -5.8 percentage of central pulse pressure | Standard Error 1.3 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Day 1 (N = 7, 8) | 0.4 percentage of central pulse pressure | Standard Error 0.9 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | Day 10 (N = 6, 8) | 2.4 percentage of central pulse pressure | Standard Error 1.1 |
Comparison: Day 1p-value: <0.000190% CI: [-5, -3.7]Mixed Models Analysis
Comparison: Day 10p-value: 0.00190% CI: [-10.7, -5.7]Mixed Models Analysis
Secondary
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)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -3.7 percentage of central pulse pressure | Standard Error 1.7 |
| Panel A - MK-8150 5 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -2.3 percentage of central pulse pressure | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -9.3 percentage of central pulse pressure | Standard Error 0.5 |
| Panel B - MK-8150 10 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -9.9 percentage of central pulse pressure | Standard Error 2.1 |
| Panel C - MK-8150 20 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -11.7 percentage of central pulse pressure | Standard Error 3.3 |
| Panel C - MK-8150 20 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -10.9 percentage of central pulse pressure | Standard Error 1.7 |
| Panel D - MK-8150 15 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -5.8 percentage of central pulse pressure | Standard Error 1.9 |
| Panel D - MK-8150 15 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -7.2 percentage of central pulse pressure | Standard Error 1.5 |
| Panel E - MK-8150 3/2 mg | 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) | Day 1 (N = 6, 6, 6, 5, 8) | -3.3 percentage of central pulse pressure | Standard Error 1 |
| Panel E - MK-8150 3/2 mg | 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) | Day 10 (N = 5, 6, 4, 5, 8) | -5.4 percentage of central pulse pressure | Standard Error 1.4 |
Comparison: Day 1p-value: 0.84890% CI: [-3.8, 3]Mixed Models Analysis
Comparison: Day 1p-value: <0.000190% CI: [-8, -4]Mixed Models Analysis
Comparison: Day 1p-value: 0.02590% CI: [-14.4, -2.4]Mixed Models Analysis
Comparison: Day 1p-value: 0.04490% CI: [-7, -0.8]Mixed Models Analysis
Comparison: Day 10p-value: 0.13990% CI: [-0.4, 6.6]Mixed Models Analysis
Comparison: Day 10p-value: 0.08890% CI: [-8.9, -0.2]Mixed Models Analysis
Comparison: Day 10p-value: 0.02390% CI: [-9.3, -1.6]Mixed Models Analysis
Comparison: Day 10p-value: 0.87890% CI: [-4.5, 3.8]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Day 1 (N = 12, 6) | -4.9 percentage of pulse pressure | Standard Error 1 |
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Day 28 (N = 10, 6) | -10.6 percentage of pulse pressure | Standard Error 1.9 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Day 1 (N = 12, 6) | -4.5 percentage of pulse pressure | Standard Error 1.2 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | Day 28 (N = 10, 6) | -4.8 percentage of pulse pressure | Standard Error 2.1 |
Comparison: Day 1p-value: 0.8390% CI: [-3.2, 2.5]Mixed Models Analysis
Comparison: Day 28p-value: 0.06390% CI: [-10.8, -0.7]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)
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. Baseline was Day 1 pre-dose value (determined separately in each period).
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -4.6 mm Hg | Standard Error 1.8 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -1.8 mm Hg | Standard Error 1.3 |
p-value: 0.03890% CI: [-4.9, -0.8]Mixed Models Analysis
Secondary
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)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | -3.5 mm Hg | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | 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) | -8.1 mm Hg | Standard Error 1.9 |
| Panel C - MK-8150 20 mg | 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) | -9.9 mm Hg | Standard Error 1.8 |
| Panel D - MK-8150 15 mg | 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) | -7.8 mm Hg | Standard Error 3 |
| Panel E - MK-8150 3/2 mg | 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) | -5.7 mm Hg | Standard Error 2.3 |
p-value: 0.51290% CI: [-3.4, 7.7]Mixed Models Analysis
p-value: 0.42990% CI: [-7.5, 2.7]Mixed Models Analysis
p-value: 0.16690% CI: [-9.3, 0.8]Mixed Models Analysis
p-value: 0.59190% CI: [-8.6, 4.5]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -5.7 mm Hg | Standard Error 1.5 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -8.7 mm Hg | Standard Error 2.4 |
p-value: 0.31790% CI: [-2.1, 7.9]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -10.0 mm Hg | Standard Error 2 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -9.6 mm Hg | Standard Error 1.6 |
p-value: 0.87790% CI: [-4.9, 4.1]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -5.3 mm Hg | Standard Error 1.7 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -5.6 mm Hg | Standard Error 1.4 |
p-value: 0.9190% CI: [-4.6, 5.2]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -7.7 mm Hg | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -7.2 mm Hg | Standard Error 3.4 |
p-value: 0.89290% CI: [-7.1, 6.1]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)
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. Baseline was Day 1 pre-dose value.
Time frame: Pre-dose and 2, 3, 4, 6, 8, 12 and 24 hours post dose
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -4.9 mmHg | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs cDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -4.3 mmHg | Standard Error 1.5 |
p-value: 0.78690% CI: [-4, 2.9]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)
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. Baseline was Day 1 pre-dose value (determined separately in each period).
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -8.9 mm Hg | Standard Error 1.8 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -6.3 mm Hg | Standard Error 1.5 |
p-value: 0.04890% CI: [-4.7, -0.6]Mixed Models Analysis
Secondary
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)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | -2.9 mm Hg | Standard Error 2.3 |
| Panel B - MK-8150 10 mg | 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) | -8.2 mm Hg | Standard Error 2.1 |
| Panel C - MK-8150 20 mg | 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) | -13.6 mm Hg | Standard Error 2.5 |
| Panel D - MK-8150 15 mg | 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) | -8.1 mm Hg | Standard Error 2.3 |
| Panel E - MK-8150 3/2 mg | 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) | -5.8 mm Hg | Standard Error 2.1 |
p-value: 0.36590% CI: [-2.5, 8.3]Mixed Models Analysis
p-value: 0.42490% CI: [-7.4, 2.6]Mixed Models Analysis
p-value: 0.02590% CI: [-13.3, -2.2]Mixed Models Analysis
p-value: 0.47590% CI: [-7.5, 3]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -0.9 mm Hg | Standard Error 1.5 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -4.1 mm Hg | Standard Error 1.4 |
p-value: 0.12890% CI: [-0.3, 6.8]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -9.3 mm Hg | Standard Error 1.7 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -4.1 mm Hg | Standard Error 2.9 |
p-value: 0.16190% CI: [-11.4, 1]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -6.5 mm Hg | Standard Error 1.6 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -6.1 mm Hg | Standard Error 1.1 |
p-value: 0.8790% CI: [-4.4, 3.7]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -10.3 mm Hg | Standard Error 1.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -9.6 mm Hg | Standard Error 2.4 |
p-value: 0.81690% CI: [-5.4, 4]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -6.5 mm Hg | Standard Error 1.3 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -5.3 mm Hg | Standard Error 1.5 |
p-value: 0.56590% CI: [-4.4, 2.1]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H)
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. Baseline was Day 1 pre-dose value (determined separately in each period).
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -15.0 mm Hg | Standard Error 3.5 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 10 Dose in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel H) | -12.6 mm Hg | Standard Error 1.8 |
p-value: 0.23890% CI: [-6, 1.2]Mixed Models Analysis
Secondary
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)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | 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) | -4.5 mm Hg | Standard Error 3.6 |
| Panel B - MK-8150 10 mg | 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) | -10.6 mm Hg | Standard Error 1.7 |
| Panel C - MK-8150 20 mg | 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) | -15.3 mm Hg | Standard Error 1.2 |
| Panel D - MK-8150 15 mg | 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) | -9.0 mm Hg | Standard Error 2.9 |
| Panel E - MK-8150 3/2 mg | 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) | -10.0 mm Hg | Standard Error 2.6 |
p-value: 0.24890% CI: [-2.5, 13.5]Mixed Models Analysis
p-value: 0.83690% CI: [-5.6, 4.4]Mixed Models Analysis
p-value: 0.10990% CI: [-10.7, 0.1]Mixed Models Analysis
p-value: 0.78590% CI: [-5.4, 7.5]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -0.4 mm Hg | Standard Error 3.5 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel E) | -7.1 mm Hg | Standard Error 1.3 |
p-value: 0.0990% CI: [0.2, 13.2]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F)
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. Baseline for Day 1 was Day 1 pre-dose value; Baseline for Day 6-15 was Day 6 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -12.8 mm Hg | Standard Error 2.8 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 15 Dose in Elderly Male and Female Participants With Mild to Moderate Hypertension Administered Single and Multiple Doses of MK-8150 and Placebo (Panel F) | -11.7 mm Hg | Standard Error 3.2 |
p-value: 0.82790% CI: [-9.3, 7.2]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -6.9 mm Hg | Standard Error 2.5 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) | -6.5 mm Hg | Standard Error 2.1 |
p-value: 0.90690% CI: [-6.6, 5.7]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -12.4 mm Hg | Standard Error 2.4 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel I) | -14.2 mm Hg | Standard Error 1.8 |
p-value: 0.57190% CI: [-3.4, 6.9]Mixed Models Analysis
Secondary
Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J)
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. Baseline was Day 1 pre-dose value.
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
Population: All participants who met protocol entry criteria, received study drug and had data available for the measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-8150 5 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -9.2 mm Hg | Standard Error 2.2 |
| Panel B - MK-8150 10 mg | Change From Baseline in TWA0-24hrs pSBP Following Day 28 Dose in Male Participants With Mild to Moderate Hypertension Administered Multiple Doses of MK-8150 and Placebo (Panel J) | -5.5 mm Hg | Standard Error 2.2 |
p-value: 0.26390% CI: [-9.3, 1.8]Mixed Models Analysis