A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-3614
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Panel A - Healthy
Healthy participants receive single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There is at least a 7-day washout between the 4 dosing periods. All doses were administered after an 8-hour fast except for Period 3. Period 3 dose was administered after the ingestion of a high-fat breakfast.
干预措施: MK-3614 (Drug)
Panel B - Healthy
Healthy participants receive single oral dose of MK-3614 0.5 mg. 0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo. There is at least a 7-day washout between the 4 dosing periods. All doses were administered after an 8-hour fast
干预措施: MK-3614 (Drug)
Panel C - Hypertensive
Hypertensive participants receive single oral dose of MK-3614 0.75 mg. 0.5 mg. 0.75 mg, 0.75 mg or matching placebo. There is at least a 7-day washout between the 4 dosing period. All doses were administered after an 8-hour fast
干预措施: MK-3614 (Drug)
结局指标
主要结局
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
时间窗: 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.
Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants
时间窗: 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
Time to Cmax (Tmax) of MK-3614- Healthy Participants
时间窗: 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 of MK-3614- Hypertensive Participants
时间窗: 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 Brachial Arterial Systolic Blood Pressure - Healthy Participants
时间窗: 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.
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants
时间窗: 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.
Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants
时间窗: 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.
Maximum Concentration (Cmax) of MK-3614- Healthy Participants
时间窗: 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.
Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants
时间窗: 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.
Time to Cmax (Tmax) of MK-3614- Hypertensive Participants
时间窗: 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
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
时间窗: 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 - Hypertensive Participants
时间窗: 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.
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants
时间窗: 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.
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants
时间窗: 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
Change From Baseline in Heart Rate - Healthy Participants
时间窗: 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 - Hypertensive Participants
时间窗: 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.
Change From Baseline in Heart Rate - Hypertensive Participants
时间窗: 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 Diastolic Blood Pressure - Hypertensive Participants
时间窗: 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.
次要结局
- Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants(Baseline and 24 hours postdose for each dose level)
- 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)
- 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)
- Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants(Baseline and 24 hours postdose for each dose level)
- Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants(Baseline and 24 hours postdose for each dose level)