Phase 1
Completed N=103
A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002)
Hypertension · Isolated Systolic Hypertension
Source: ClinicalTrials.gov NCT01656408 ↗
Enrolled (actual)
103
Serious AEs
0.0%
Results posted
Apr 2016
Primary outcomePrimary: Number of Participants With an Adverse Event (AE) — 4; 5; 6; 3 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With an Adverse Event (AE) |
4; 5; 6; 3; 4; 3 | — |
| PRIMARY Number of Participants Discontinued From Study Drug Due to Meeting Hemodynamic Stopping Rules |
3; 0; 1; 0; 2; 1 | — |
| 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) |
-5.3; -15.3; -19.5; -12.8; -5.4; -6.2 | 0.978 |
| 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) |
0.0; -7.2; -12.3; -4.0; -1.9; -3.6 | 0.635 |
| 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) |
-16.3; -15.5; -11.8; -15.5; -10.6; -16.9 | 0.855 |
| 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) |
0.5; 2.0; 1.6; 0.8; 2.5; 0.7 | 0.563 |
| 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) |
-16.1; -20.5; -17.2; -24.6; -20.8; -23.8 | 0.357 |
| 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) |
-1.2; -1.5; -0.2; -2.1; -1.6; -5.8 | 0.942 |
| PRIMARY Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) |
-8.0; 2.8; -8.3; -2.3 | 0.025 sig |
| PRIMARY Change From Baseline in TWA0-24hrs HR in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) |
-1.1; -1.1; 0.5; 0.8; 2.3; 0.2 | 0.999 |
| 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) |
-10.1; -4.5; -7.7; -1.8 | 0.099 |
| 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) |
-2.4; 0.0; -0.6; -2.0 | 0.281 |
| 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) |
-11.2; -7.4; -15.2; -14.4 | 0.279 |
| 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) |
0.3; -0.5; 1.2; -2.8; 0.8; -1.6 | 0.756 |
| 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) |
-16.7; -5.4; -11.5; -5.4 | 0.003 sig |
| 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) |
-3.0; -1.6; -0.6; -2.8; -1.2; -2.6 | 0.691 |
| 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) |
1.84; 3.22; 6.97; 5.16; 6.76; 12.3 | — |
| 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) |
0.183; 0.353; 0.656; 0.502; 0.440; 0.784 | — |
| 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) |
1; 1; 1.25; 1; 1; 0.75 | — |
| 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) |
70.7; 78.6; 46.7; 58.0 | — |
| 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) |
1.17; 2.37 | — |
| 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) |
0.129; 0.268 | — |
| 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) |
1; 1 | — |
| 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) |
85.0; 82.1 | — |
| 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) |
1.08; 2.23; 2.98; 6.58 | — |
| 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) |
0.109; 0.208; 0.192; 0.425 | — |
| 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) |
1; 1; 1; 1 | — |
| 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) |
68.1; 92.6 | — |
| PRIMARY AUC0-24 of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) |
8.08; 65.5 | — |
| PRIMARY Cmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) |
0.664; 4.05 | — |
| PRIMARY Tmax of MK-8150 in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) |
1.0; 1.5 | — |
| PRIMARY t1/2 of MK-8150 Determined Following Day 28 Dose in Healthy Male Participants Administered Multiple Doses of MK-8150 (Panel G) |
51.8 | — |
| PRIMARY AUC0-24 of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) |
3.56; 25.1 | — |
| PRIMARY Cmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) |
0.395; 1.71 | — |
| PRIMARY Tmax of MK-8150 in Male and Female Participants With Resistant Hypertension Administered Multiple Doses of MK-8150 (Panel H) |
1.0; 1.0 | — |
| 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) |
69.6 | — |
| 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) |
1.80; 3.80; 39.1; 28.5 | — |
| 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) |
0.213; 0.395; 2.72; 1.75 | — |
| 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) |
0.75; 1.0; 0.5; 1 | — |
| 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) |
73.9; 81.0 | — |
| 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) |
-3.7; -9.3; -11.7; -7.2; -3.3; -2.3 | 0.848 |
| 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) |
-3.5; -8.1; -9.9; -7.8; -5.7 | 0.512 |
| 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) |
-4.5; -10.6; -15.3; -9.0; -10.0 | 0.248 |
| 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) |
-2.9; -8.2; -13.6; -8.1; -5.8 | 0.365 |
| 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) |
-3.8; -2.6; -5.2; -1.0; -3.5; 0.3 | 0.715 |
| 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) |
-5.7; -8.7 | 0.317 |
| 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) |
-0.4; -7.1 | 0.090 |
| 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) |
-0.9; -4.1 | 0.128 |
| 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) |
-4.8; -2.5; -5.1; 0.5; -6.8; 0.9 | 0.477 |
| 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) |
-10.0; -9.6 | 0.877 |
| 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) |
-12.8; -11.7 | 0.827 |
| 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) |
-9.3; -4.1 | 0.161 |
| SECONDARY Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Multiple Doses of MK-8150 and Placebo (Panel G) |
-11.8; -1.3; -14.2; -1.4 | 0.046 sig |
| 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) |
-5.3; -5.6 | 0.910 |
| 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) |
-6.9; -6.5 | 0.906 |
| 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) |
-6.5; -6.1 | 0.870 |
| 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) |
-3.9; 0.4; -5.8; 2.4 | <0.0001 sig |
| 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) |
-4.6; -1.8 | 0.038 sig |
| 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) |
-15.0; -12.6 | 0.238 |
| 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) |
-8.9; -6.3 | 0.048 sig |
| 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) |
-4.9; -4.5; -10.6; -4.8 | 0.830 |
| 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) |
-7.7; -7.2 | 0.892 |
| 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) |
-12.4; -14.2 | 0.571 |
| 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) |
-10.3; -9.6 | 0.816 |
| 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) |
-10.4; -5.9; -9.9; -6.1 | 0.061 |
| 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) |
-4.9; -4.3 | 0.786 |
| 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) |
-9.2; -5.5 | 0.263 |
| 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) |
-6.5; -5.3 | 0.565 |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01656408). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.