Hypertension
Conditions
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.
Interventions
DRUGMK-3614
DRUGComparator: Placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants | 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. |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 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. |
| Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 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. |
| Time to Cmax (Tmax) of MK-3614- Healthy Participants | 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. |
| Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 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. |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants | 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 |
| Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants | 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 |
| Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | 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. |
| Time to Cmax (Tmax) of MK-3614- Hypertensive Participants | 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 |
| Change From Baseline in Heart Rate - Hypertensive Participants | 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. |
| Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants | 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. |
| Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants | 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 |
| Change From Baseline in Heart Rate - Healthy Participants | 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. |
| Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | 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. |
| Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 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. |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 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. |
| Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants | 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. |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 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. |
| Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | 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. |
| Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants | 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. |
| Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants | 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. |
| Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants | 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. |
| Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 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. |
| Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants | 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. |
| Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants | 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. |
| Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants | 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. |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 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. |
Participant flow
Recruitment details
Three panels, each consisting of 8 participants (8 healthy young males in Panel A and Panel B; and 8 with mild-to-moderate hypertension in Panel C) were randomized to receive either MK-3614 or matching placebo in a 3:1 ratio, respectively, in up to 4 treatment periods in Panel A, Panel B and Panel C.
Pre-assignment details
Each period of each panel (with exception of 0.25 mg fasted/fed periods) will be re-randomized to receive either study drug or placebo, i.e., a participant could be assigned to receive study drug in one period and placebo in another. The same participants will receive 0.25 mg MK-3614 in a fasted and fed state.
Participants by arm
| Arm | Count |
|---|---|
| Panel A - Healthy Healthy participants received a single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods. | 8 |
| Panel B - Healthy Healthy participants received a 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 was at least a 7-day washout between the 4 dosing periods. | 8 |
| Panel C - Hypertensive Hypertensive participants received a single oral dose of MK-3614 0.75 mg, 0.5 mg, 0.75 mg, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods. | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Panel A - Healthy | Panel B - Healthy | Panel C - Hypertensive | Total |
|---|---|---|---|---|
| Age, Continuous | 28.8 years STANDARD_DEVIATION 6.8 | 33.4 years STANDARD_DEVIATION 7 | 46.6 years STANDARD_DEVIATION 9.4 | 36.3 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 7 | 0 / 8 | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 4 / 5 | 2 / 6 | 4 / 6 | 4 / 6 | 4 / 6 | 1 / 5 | 3 / 5 | 4 / 7 | 6 / 8 | 3 / 5 | 4 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 7 | 0 / 8 | 0 / 5 | 0 / 7 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 9.2 hr | Standard Deviation 4.5 |
| 1.25 mg MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 10.1 hr | Standard Deviation 2.3 |
| 0.25 mg w/ Food MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 13.1 hr | Standard Deviation 1.2 |
| 0.75 mg MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 9.1 hr | Standard Deviation 3 |
| Placebo Panel A | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 9.7 hr | Standard Deviation 3.6 |
| 0.5 mg MK-3614 Panel B | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 9.5 hr | Standard Deviation 2.1 |
| 0.75 mg MK-3614 Panel B | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 11.7 hr | Standard Deviation 4.1 |
| 0.25 mg b.i.d. MK-3614 Panel B | Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants | 14.7 hr | Standard Deviation 6 |
Primary
Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants
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
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint. Data were summarized by dose taken and not by sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants | 9.1 hr | Standard Deviation 2.8 |
| 1.25 mg MK-3614 Panel A | Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants | 8.7 hr | Standard Deviation 1.4 |
Primary
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 83.8 nM•h | Standard Deviation 53.1 |
| 1.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 412.0 nM•h | Standard Deviation 96.4 |
| 0.25 mg w/ Food MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 83.8 nM•h | Standard Deviation 9.46 |
| 0.75 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 223.0 nM•h | Standard Deviation 83.1 |
| Placebo Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 173.0 nM•h | Standard Deviation 82 |
| 0.5 mg MK-3614 Panel B | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | 168.0 nM•h | Standard Deviation 27.7 |
| 0.75 mg MK-3614 Panel B | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | NA nM•h | — |
| 0.25 mg b.i.d. MK-3614 Panel B | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants | NA nM•h | — |
Primary
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants
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
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint. Data were summarized by dose taken and not by sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants | 253.0 nM•h | Standard Deviation 52 |
| 1.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants | 134.0 nM•h | Standard Deviation 39.5 |
Primary
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | -1.7 mmHg | Standard Deviation 3.1 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | 0.8 mmHg | Standard Deviation 6.7 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | -2.8 mmHg | Standard Deviation 5.4 |
| 0.75 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | -1.0 mmHg | Standard Deviation 5.6 |
| Placebo Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | -1.8 mmHg | Standard Deviation 4 |
| 0.5 mg MK-3614 Panel B | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | 3.2 mmHg | Standard Deviation 6 |
| 0.75 mg MK-3614 Panel B | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants | -0.6 mmHg | Standard Deviation 3.3 |
Primary
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants | 0.3 mmHg | Standard Deviation 9.3 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants | -4.4 mmHg | Standard Deviation 6.5 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants | -9.1 mmHg | Standard Deviation 6.9 |
Primary
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -3.3 mmHg | Standard Deviation 4.8 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | 2.4 mmHg | Standard Deviation 2.3 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -2.6 mmHg | Standard Deviation 5.3 |
| 0.75 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -1.0 mmHg | Standard Deviation 9.2 |
| Placebo Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -3.1 mmHg | Standard Deviation 5.7 |
| 0.5 mg MK-3614 Panel B | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -3.0 mmHg | Standard Deviation 8 |
| 0.75 mg MK-3614 Panel B | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants | -0.2 mmHg | Standard Deviation 7.4 |
Primary
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants | -5.2 mmHg | Standard Deviation 14.2 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants | -10.0 mmHg | Standard Deviation 13 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants | -18.1 mmHg | Standard Deviation 15.6 |
Primary
Change From Baseline in Heart Rate - Healthy Participants
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.
Time frame: Baseline and 24 hours post-dose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Heart Rate - Healthy Participants | -4.7 Beats per minute (bpm) | Standard Deviation 3.7 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Heart Rate - Healthy Participants | -0.6 Beats per minute (bpm) | Standard Deviation 7.2 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Heart Rate - Healthy Participants | 5.4 Beats per minute (bpm) | Standard Deviation 7.2 |
| 0.75 mg MK-3614 Panel A | Change From Baseline in Heart Rate - Healthy Participants | 2.5 Beats per minute (bpm) | Standard Deviation 4.8 |
| Placebo Panel A | Change From Baseline in Heart Rate - Healthy Participants | -0.3 Beats per minute (bpm) | Standard Deviation 5.9 |
| 0.5 mg MK-3614 Panel B | Change From Baseline in Heart Rate - Healthy Participants | 6.3 Beats per minute (bpm) | Standard Deviation 11.8 |
| 0.75 mg MK-3614 Panel B | Change From Baseline in Heart Rate - Healthy Participants | 3.8 Beats per minute (bpm) | Standard Deviation 6.6 |
Primary
Change From Baseline in Heart Rate - Hypertensive Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Change From Baseline in Heart Rate - Hypertensive Participants | 0.7 bpm | Standard Deviation 8.1 |
| 1.25 mg MK-3614 Panel A | Change From Baseline in Heart Rate - Hypertensive Participants | 0.8 bpm | Standard Deviation 10.7 |
| 0.25 mg w/ Food MK-3614 Panel A | Change From Baseline in Heart Rate - Hypertensive Participants | -8.4 bpm | Standard Deviation 8.5 |
Primary
Maximum Concentration (Cmax) of MK-3614- Healthy Participants
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 4.9 nM | Standard Deviation 1.68 |
| 1.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 29.8 nM | Standard Deviation 5.2 |
| 0.25 mg w/ Food MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 3.6 nM | Standard Deviation 1.09 |
| 0.75 mg MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 17.0 nM | Standard Deviation 4.48 |
| Placebo Panel A | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 11.5 nM | Standard Deviation 4.22 |
| 0.5 mg MK-3614 Panel B | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 13.4 nM | Standard Deviation 2.24 |
| 0.75 mg MK-3614 Panel B | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 5.1 nM | Standard Deviation 0.55 |
| 0.25 mg b.i.d. MK-3614 Panel B | Maximum Concentration (Cmax) of MK-3614- Healthy Participants | 7.1 nM | Standard Deviation 1.5 |
Primary
Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants
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
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint. Data were summarized by dose taken and not by sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants | 19.1 nM | Standard Deviation 3.88 |
| 1.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants | 10.9 nM | Standard Deviation 1.55 |
Primary
Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants
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.
Time frame: up to 7 days for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants | 75.0 Percentage of Participants |
| 1.25 mg MK-3614 Panel A | Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants | 60.0 Percentage of Participants |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants | 57.1 Percentage of Participants |
Primary
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
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.
Time frame: up to 7 days for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 100.0 Percentage of Participants |
| 1.25 mg MK-3614 Panel A | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 100.0 Percentage of Participants |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 80.0 Percentage of Participants |
| 0.75 mg MK-3614 Panel A | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 33.3 Percentage of Participants |
| Placebo Panel A | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 66.7 Percentage of Participants |
| 0.5 mg MK-3614 Panel B | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 66.7 Percentage of Participants |
| 0.75 mg MK-3614 Panel B | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 66.7 Percentage of Participants |
| 0.25 mg b.i.d. MK-3614 Panel B | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 20.0 Percentage of Participants |
| 0.25 mg t.i.d MK-3614 Panel B | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 60.0 Percentage of Participants |
| Placebo Panel B | Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants | 57.1 Percentage of Participants |
Primary
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
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.
Time frame: up to 7 days for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 1.25 mg MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 0.75 mg MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| Placebo Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 0.5 mg MK-3614 Panel B | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 16.7 Percentage of Participants |
| 0.75 mg MK-3614 Panel B | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 0.25 mg b.i.d. MK-3614 Panel B | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| 0.25 mg t.i.d MK-3614 Panel B | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
| Placebo Panel B | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants
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.
Time frame: up to 7 days for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants | 12.5 Percentage of Participants |
| 1.25 mg MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants | 0.0 Percentage of Participants |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants | 14.3 Percentage of Participants |
Primary
Time to Cmax (Tmax) of MK-3614- Healthy Participants
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| 1.25 mg MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| 0.25 mg w/ Food MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 6.0 hour (hr) |
| 0.75 mg MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| Placebo Panel A | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| 0.5 mg MK-3614 Panel B | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| 0.75 mg MK-3614 Panel B | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 4.0 hour (hr) |
| 0.25 mg b.i.d. MK-3614 Panel B | Time to Cmax (Tmax) of MK-3614- Healthy Participants | 16.0 hour (hr) |
Primary
Time to Cmax (Tmax) of MK-3614- Hypertensive Participants
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
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in in Panel C who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint. Data were summarized by dose taken and not by sequence.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.25 mg MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Hypertensive Participants | 4.0 hr |
| 1.25 mg MK-3614 Panel A | Time to Cmax (Tmax) of MK-3614- Hypertensive Participants | 4.0 hr |
Secondary
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panels A who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 83.8 nM•h | Standard Deviation 53.1 |
| 1.25 mg MK-3614 Panel A | Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 83.8 nM•h | Standard Deviation 9.46 |
Secondary
Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
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.
Time frame: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Population: All participants in Panel A who received at least 1 dose of study drug and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and had available data for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 4.85 nM | Standard Deviation 1.68 |
| 1.25 mg MK-3614 Panel A | Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed | 3.56 nM | Standard Deviation 1.09 |
Secondary
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -4.7 Percentage change | Standard Deviation 10.1 |
| 1.25 mg MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -5.2 Percentage change | Standard Deviation 7.9 |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -0.8 Percentage change | Standard Deviation 3.1 |
| 0.75 mg MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -1.8 Percentage change | Standard Deviation 6 |
| Placebo Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -3.0 Percentage change | Standard Deviation 4 |
| 0.5 mg MK-3614 Panel B | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | -1.5 Percentage change | Standard Deviation 6 |
| 0.75 mg MK-3614 Panel B | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants | 0.8 Percentage change | Standard Deviation 4.1 |
Secondary
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants | 2.0 Percentage change | Standard Deviation 6.4 |
| 1.25 mg MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants | -2.3 Percentage change | Standard Deviation 4.9 |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants | 1.1 Percentage change | Standard Deviation 5 |
Secondary
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
Secondary
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.
Secondary
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Panel A | Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants | -22.3 Percentage change | Standard Deviation 26.3 |
| 0.75 mg MK-3614 Panel B | Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants | -5.0 Percentage change | Standard Deviation 12.8 |
Secondary
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 mg MK-3614 Panel A | Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants | -9.3 Percentage change | Standard Deviation 12.9 |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants | -19.5 Percentage change | Standard Deviation 21.9 |
Secondary
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 mg MK-3614 Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.1 Percentage change | Standard Deviation 0.1 |
| 1.25 mg MK-3614 Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.0 Percentage change | Standard Deviation 0 |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.2 Percentage change | Standard Deviation 0.1 |
| Placebo Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.0 Percentage change | Standard Deviation 0.1 |
| 0.5 mg MK-3614 Panel B | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.0 Percentage change | Standard Deviation 0 |
| 0.75 mg MK-3614 Panel B | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants | 0.0 Percentage change | Standard Deviation 0.1 |
Secondary
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants
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.
Time frame: Baseline and 24 hours postdose for each dose level
Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 mg MK-3614 Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants | 0.2 Percentage change | Standard Deviation 0.2 |
| 0.25 mg w/ Food MK-3614 Panel A | Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants | 0.0 Percentage change | Standard Deviation 0.2 |