Phase 1
Completed N=25
A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)
Source: ClinicalTrials.gov NCT01798849 ↗Enrolled (actual)
25
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcomePrimary: Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants — 50.0; 66.7; 50.0; 100.0 Percentage of Participants
Summary
This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants |
50.0; 66.7; 50.0; 100.0; 100.0; 83.3 | — |
| PRIMARY Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants |
-1.83; -2.27; -4.21; -4.25; -6.22; -6.64 | 0.732 |
| PRIMARY Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants |
50.0; 33.3; 66.7; 77.8; 75.0 | — |
| PRIMARY Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants |
0.0; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants |
-3.56; -4.76; -7.55; -7.86; -1.22 | 0.165 |
| SECONDARY Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants |
-4.34; -2.43; -3.69; -4.50; -6.56; -7.04 | 0.128 |
| SECONDARY Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants |
0.46; 5.55; 4.71; 7.44; 9.29; 8.85 | 0.212 |
| SECONDARY Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants |
-1.73; -2.31; -2.82; -0.26; -4.23; -3.85 | 0.202 |
| SECONDARY Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants |
-3.40; -4.17; -7.29; -9.16; -0.87 | 0.042 sig |
| SECONDARY Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants |
-0.92; -0.74; 0.87; 7.68; -1.46 | 0.638 |
| SECONDARY TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants |
-2.30; -2.57; -3.94; -5.43; -1.65 | 0.677 |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants |
67; 128; 218; 464; 694; 793 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants |
103.3; 216.8; 368.5; 724.7; 1157.6; 1293.3 | — |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants |
113; 232; 391; 757; 1195; 1342 | — |
| SECONDARY Maximum Concentration (Cmax) of MK-8892 - Healthy Participants |
4.8; 8.5; 17.9; 35.6; 49.0; 52.8 | — |
| SECONDARY Time to Cmax (Tmax) of MK-8892 - Healthy Participants |
4; 4; 4; 4; 4; 5 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants |
17.9; 20.6; 20.1; 17.7; 15.6; 20.9 | — |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants |
79; 158; 285; 806; 714 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants |
150.2; 317.3; 522.3; 1700.2; 1538.8 | — |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants |
164.0; 346.0; 557.0; 1947.0; 1760.0 | — |
| SECONDARY Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants |
4.9; 9.8; 17.6; 48.9; 47.1 | — |
| SECONDARY Time to Cmax (Tmax) of MK-8892- Hypertensive Participants |
3; 4; 6; 4; 4 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants |
23.5; 24.5; 21.6; 28.8; 26.3 | — |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed |
218.2; 278.2 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed |
368.5; 494.6 | — |
| SECONDARY Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed |
390.0; 518.5 | — |
| SECONDARY Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed |
17.9; 20.5 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed |
20.1; 20.5 | — |
Eligibility Criteria
Inclusion Criteria
- Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication
- Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2
- Healthy (with the exception of hypertensive subjects in Panel C)
- No clinically significant abnormality on electrocardiogram (ECG)
- No history of clinically significant cardiac disease
- No history of heart failure
- Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months
Exclusion Criteria
- Mentally or legally incapacitated
- History of stroke, chronic seizures, or major neurological disorder
- History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
- Functional disability that can interfere with rising from a sitting position to the standing position
- History of cancer (malignancy)
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
- Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)
- Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
- Has participated in another investigational trial within 4 weeks
- Unable to refrain from or anticipates the use of any medication during the study
- Anticipates using medication for erectile dysfunction during the study
- Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
- Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study
- Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day
- Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day
- Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
Data sourced from ClinicalTrials.gov (NCT01798849). 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.