A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01798849
• Date of registration: 22/02/2013
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)
• Scientific title: A Single Rising Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892
• Date of first enrolment: March 15, 2013
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01798849
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Belgium

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: MK-8892

Drug: Placebo for MK-8892

Primary Outcome(s)

Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants [Time Frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)]

Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants [Time Frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)]

Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants [Time Frame: up to 7 weeks]

Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants [Time Frame: up to 7 weeks]

Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants [Time Frame: up to 7 weeks]

Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants [Time Frame: up to 7 weeks]

Secondary Outcome(s)

Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose]

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 [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Maximum Concentration (Cmax) of MK-8892 - Healthy Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants [Time Frame: Predose to 24 hours Postdose (for each Dosing Period of Each Panel)]

Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants [Time Frame: Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)]

Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Time to Cmax (Tmax) of MK-8892 - Healthy Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose]

Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants [Time Frame: Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)]

Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

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 [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants [Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose]

Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

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 [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants [Time Frame: Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)]

Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants [Time Frame: Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)]

Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants [Time Frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)]

Time to Cmax (Tmax) of MK-8892- Hypertensive Participants [Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose]

Secondary ID(s)

8892-001

2012-005472-34

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/07/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01798849