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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3614-001 | Other Identifier | Merck | |
| 2010_525 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panel A - Healthy | Experimental | 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. |
|
| Panel B - Healthy | Experimental | 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 |
|
| Panel C - Hypertensive | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-3614 | Drug |
| ||
| Comparator: Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to 7 days for each dose level |
| 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. | up to 7 days for each dose level |
| 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. | up to 7 days for each dose level |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants |
| 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 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Panel B - Healthy |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Number | Percentage of Participants | up to 7 days for each dose level |
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Up to 7 days postdose for each dose level (up to 15 weeks total)
All participants that received at least 1 dose of study drug and had data available for endpoint.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.25 mg MK-3614 Panel A | Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block second degree | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| Drug |
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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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
| 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | 1.25 mg MK-3614 Panel A | Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast |
| OG002 | 0.25 mg w/ Food MK-3614 Panel A | Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest |
| OG003 | 0.75 mg MK-3614 Panel A | Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast |
| OG004 | Placebo Panel A | Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast |
| OG005 | 0.5 mg MK-3614 Panel B | Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast |
| OG006 | 0.75 mg MK-3614 Panel B | Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast |
| OG007 | 0.25 mg b.i.d. MK-3614 Panel B | Participants received a single daily dose of 0.25 mg MK-3614 b.i.d. |
| OG008 | 0.25 mg t.i.d MK-3614 Panel B | Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d. |
| OG009 | Placebo Panel B | Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Number | Percentage of Participants | up to 7 days for each dose level |
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| 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. | All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Number | Percentage of Participants | up to 7 days for each dose level |
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| 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. | All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Number | Percentage of Participants | up to 7 days for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | nM•h | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | nM | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | 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. | Posted | Median | Full Range | hour (hr) | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | hr | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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 | 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. | Posted | Mean | Standard Deviation | nM•h | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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 | 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. | Posted | Mean | Standard Deviation | nM | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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 | 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. | Posted | Median | Full Range | hr | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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 | 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. | Posted | Mean | Standard Deviation | hr | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Beats per minute (bpm) | Baseline and 24 hours post-dose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | mmHg | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | mmHg | Baseline and 24 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | bpm | Baseline and 24 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline and 24 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline and 24 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | nM•h | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | 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. | Posted | Mean | Standard Deviation | nM | Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 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. | All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint. | Posted | Mean | Standard Deviation | Percentage change | Baseline and 24 hours postdose for each dose level |
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| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | 1.25 mg MK-3614 Panel A | Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | 0.25 mg w/ Food MK-3614 Panel A | Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest | 0 | 5 | 0 | 5 | 4 | 5 |
| EG003 | 0.75 mg MK-3614 Panel A | Participant received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Placebo Panel A | Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast | 0 | 6 | 0 | 6 | 4 | 6 |
| EG005 | 0.5 mg MK-3614 Panel B | Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast | 0 | 6 | 0 | 6 | 4 | 6 |
| EG006 | 0.75 mg MK-3614 Panel B | Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast | 0 | 6 | 0 | 6 | 4 | 6 |
| EG007 | 0.25 mg b.i.d. MK-3614 Panel B | Participants received a single daily dose of 0.25 mg MK-3614 b.i.d. | 0 | 5 | 0 | 5 | 1 | 5 |
| EG008 | 0.25 mg t.i.d MK-3614 Panel B | Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d. | 0 | 5 | 0 | 5 | 3 | 5 |
| EG009 | Placebo Panel B | Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast | 0 | 7 | 0 | 7 | 4 | 7 |
| EG010 | 0.75 mg MK-3614 Panel C | Participant received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast | 0 | 8 | 0 | 8 | 6 | 8 |
| EG011 | 0.5 mg MK-3614 Panel C | Participants received a single oral dose of 0.5 mg MK-3614 after an 8-hour fast | 0 | 5 | 0 | 5 | 3 | 5 |
| EG012 | Placebo Panel C | Participant received a single oral dose of placebo for MK-3614 after an 8-hour fast | 0 | 7 | 0 | 7 | 4 | 7 |
| Extrasystoles | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Sinus tachycardia | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Ventricular extrasystoles | Cardiac disorders | MedDRA version 12.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 12.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA version 12.0 | Systematic Assessment |
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| Blood immunoglobulin E increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Blood pressure orthostatic decreased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Blood pressure systolic increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Heart rate increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Orthostatic heart rate response increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Red blood cell sedimentation rate increased | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| White blood cells urine positive | Investigations | MedDRA version 12.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 12.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Dysstasia | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Vibratory sense increased | Nervous system disorders | MedDRA version 12.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 12.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA version 12.0 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.