- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01104545
A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED)
June 24, 2019 updated by: Merck Sharp & Dohme LLC
A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-3614
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Panel A - Healthy
Healthy participants receive single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo.
There is at least a 7-day washout between the 4 dosing periods.
All doses were administered after an 8-hour fast except for Period 3. Period 3 dose was administered after the ingestion of a high-fat breakfast.
|
|
Experimental: Panel B - Healthy
Healthy participants receive single oral dose of MK-3614 0.5 mg.
0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo.
There is at least a 7-day washout between the 4 dosing periods.
All doses were administered after an 8-hour fast
|
|
Experimental: Panel C - Hypertensive
Hypertensive participants receive single oral dose of MK-3614 0.75 mg.
0.5 mg.
0.75 mg, 0.75 mg or matching placebo.
There is at least a 7-day washout between the 4 dosing period.
All doses were administered after an 8-hour fast
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
Time Frame: up to 7 days for each dose level
|
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product.
The percentage of participants that reported at least 1 AE was summarized.
AEs are reported by the dose taken at the time of the event.
|
up to 7 days for each dose level
|
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
Time Frame: up to 7 days for each dose level
|
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product.
The percentage of participants who were discontinued from the study due to an AE were summarized.
AEs are reported by the dose taken at the time of the event.
|
up to 7 days for each dose level
|
Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants
Time Frame: up to 7 days for each dose level
|
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product.
The percentage of participants that reported at least 1 AE was summarized.
The percentage of participants that reported at least 1 AE was summarized.
AEs are reported by the dose taken at the time of the event.
|
up to 7 days for each dose level
|
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants
Time Frame: up to 7 days for each dose level
|
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product.
The percentage of participants who were discontinued from the study due to an AE were summarized.
AEs are reported by the dose taken at the time of the event.
|
up to 7 days for each dose level
|
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in healthy participants.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Maximum Concentration (Cmax) of MK-3614- Healthy Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in healthy participants.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Time to Cmax (Tmax) of MK-3614- Healthy Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in healthy participants.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in healthy participants.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in hypertensive participants
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in hypertensive participants
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Time to Cmax (Tmax) of MK-3614- Hypertensive Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in hypertensive participants
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in hypertensive participants
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Change From Baseline in Heart Rate - Healthy Participants
Time Frame: Baseline and 24 hours post-dose for each dose level
|
Heart rate measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours post-dose for each dose level
|
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Brachial arterial systolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours postdose for each dose level
|
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Brachial arterial diastolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours postdose for each dose level
|
Change From Baseline in Heart Rate - Hypertensive Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
HR measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of sequence.
|
Baseline and 24 hours postdose for each dose level
|
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Brachial arterial systolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of sequence.
|
Baseline and 24 hours postdose for each dose level
|
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Brachial arterial diastolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device.
The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized.
Data for each specific dose were combined regardless of sequnce.
|
Baseline and 24 hours postdose for each dose level
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of 0.25 mg MK-3614 in healthy participant when administered after an 8 hour fast and after a high-fat breakfest.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
Time Frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of 0.25 mg MK-3614 when administered after an 8 hour fast and after a high-fat breakfest.
|
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
|
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery.
The change from baseline at 24 hours postdose was summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery.
The change from baseline at 24 hours postdose was summarized.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Blood was to be drawn at predose (baseline) and 3 and 24 hours postdose and bleeding time was to be assessed using a Newborn Surgicutt device.
Change in bleeding time from baseline at 24 hours postdose were to be summarized.
Due to change in number of blood draws and total blood volume restrictions, bleeding time assessment was not performed as planned.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Blood was to be drawn at predose (baseline) and 3 and 24 hours postdose and bleeding time was to be assessed using a Newborn Surgicutt device.
Change in bleeding time from baseline at 24 hours postdose were to be summarized.
Due to change in number of blood draws and total blood volume restrictions, bleeding time assessment was not performed as planned.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Blood was drawn at predose (baseline) and 1, 4, 8, and 24 hours postdose.
The change in cyclic GMP at 24 hours postdose was summarized.
Due to change in number of blood draws and total blood volume restrictions, data for GMP were only collected for first 2 periods of each panel.
Therefore only limited data were available and summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Blood was drawn at predose (baseline) and 1, 4, 8, and 24 hours postdose.
The change in cyclic GMP at 24 hours postdose was summarized.
Due to change in number of blood draws and total blood volume restrictions, data for GMP were only collected for first 2 periods of each panel.
Therefore only limited data were available and summarized.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Platelet aggregation induced by adenosine diphosphate (ADP) was measured at predose (baseline) and 3 and 24 hours postdose.
Percent inhibition from baseline at 24 hours postdose was calculated.
Due to change in number of blood draws and total blood volume restrictions, data for platelet aggregation were only collected for first 2 periods of each panel.
Therefore only limited data were available and summarized.
Data for each specific dose were combined regardless of panel.
|
Baseline and 24 hours postdose for each dose level
|
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants
Time Frame: Baseline and 24 hours postdose for each dose level
|
Platelet aggregation induced by adenosine diphosphate (ADP) was measured at predose (baseline) and 3 and 24 hours postdose.
Percent inhibition from baseline at 24 hours postdose was calculated.
Due to change in number of blood draws and total blood volume restrictions, data for platelet aggregation were only collected for first 2 periods of each panel.
Therefore only limited data were available and summarized.
|
Baseline and 24 hours postdose for each dose level
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2008
Primary Completion (Actual)
May 1, 2009
Study Completion (Actual)
May 1, 2009
Study Registration Dates
First Submitted
April 13, 2010
First Submitted That Met QC Criteria
April 13, 2010
First Posted (Estimate)
April 15, 2010
Study Record Updates
Last Update Posted (Actual)
August 8, 2019
Last Update Submitted That Met QC Criteria
June 24, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3614-001
- MK-3614-001 (Other Identifier: Merck)
- 2010_525
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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