Clinical trial NCT01104545: A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED)
Official title: A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-3614
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-04-15
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine if MK-3614, given as single doses, is safe and well tolerated in healthy males and male participants with mild to moderate hypertension.

Detailed description: Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-3614 or placebo. All doses will be administered in the fasted state, except Panel A, Period 3 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing. Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. All participants in periods of all panels (with exception of 0.25 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e., a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 0.25 mg MK-3612 in a fasted and fed state.

Eligibility criteria: Inclusion Criteria:

* Healthy participants between 18 to 45 years of age; otherwise healthy participants between 18 to 55 years of age newly diagnosed with grade 1 or 2 hypertension
* Participant is in good general health
* Participant is a nonsmoker

Exclusion Criteria:

* Participant has a history of stroke, seizure or major neurological disease
* Participant has functional disability that can interfere with rising from a sitting position to a standing position
* Participant has a family history of a bleeding or clotting disorder
* Participant has a history of cancer
* Participant is unable to refrain from or anticipates the use of any prescription or non-prescription medication during the study
* Participant consumes excessive amounts of alcohol or caffeine
* Participant has had major surgery, donated blood or participated in another investigational study in the past 4 weeks.

Primary outcomes:
measure: Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
timeFrame: up to 7 days for each dose level
measure: Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
timeFrame: up to 7 days for each dose level
measure: Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants
timeFrame: up to 7 days for each dose level
measure: Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants
timeFrame: up to 7 days for each dose level
measure: Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Maximum Concentration (Cmax) of MK-3614- Healthy Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Time to Cmax (Tmax) of MK-3614- Healthy Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Time to Cmax (Tmax) of MK-3614- Hypertensive Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Change From Baseline in Heart Rate - Healthy Participants
timeFrame: Baseline and 24 hours post-dose for each dose level
measure: Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Change From Baseline in Heart Rate - Hypertensive Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants
timeFrame: Baseline and 24 hours postdose for each dose level
Secondary outcomes:
measure: Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
timeFrame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
measure: Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants
timeFrame: Baseline and 24 hours postdose for each dose level
measure: Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants
timeFrame: Baseline and 24 hours postdose for each dose level
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References: