A Double-Blind, Randomized, Placebo-Controlled, 3-Period, Crossover Study to Evaluate the Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Subjects and Patients With Hypertension
概览
- 阶段
- 1 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Hypertension
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 38
- 主要终点
- Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment
- 状态
- 已完成
- 最后更新
- 10年前
概览
简要总结
This study will test the relationship between CBP (central blood pressure) and PBP (peripheral blood pressure) effects after single and multiple doses of Isosorbide mononitrate extended release (ISMN ER) or Amlodipine besylate in participants with hypertension.
研究者
入排标准
入选标准
- •Participant is a male or female between 30 and 65 years of age (inclusive) at the pre-study (screening)
- •Female participant of childbearing potential must have a negative pregnancy test
- •Participant has a brachial systolic blood pressure \>130 mm Hg
- •and \<180 mm Hg
- •Participant has a Body Mass Index (BMI) that is \>20 kg/m\^2 and \<35 kg/m\^2
- •Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months
排除标准
- •Female Participant is pregnant or lactating
- •Participant anticipates the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) other than acetaminophen
- •Participant is currently a user (including "recreational use") of any illicit drugs, has a history of drug or alcohol abuse within approximately 2 years, or has a positive prestudy urine drug screen
- •Participant has a condition for which there is a warning, contraindication, or precaution against the use of ISMN ER including: acute myocardial infarction or congestive heart failure, hypotension, volume depletion, and pregnancy
- •Participant has a history of significant drug allergy or any clinically significant adverse experience of a serious nature related to the administration of either a marketed or an investigational drug, including nitrates, nitrites, Amlodipine, and ISMN ER
研究组 & 干预措施
Placebo/ISMN ER/Amlodipine (Sequence 1)
Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
干预措施: Placebo
ISMN ER/Amlodipine/Placebo (Sequence 2)
Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
干预措施: Placebo
Amlodipine/Placebo/ISMN ER (Sequence 3)
Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
干预措施: Placebo
ISMN ER/Placebo/Amlodipine (Sequence 4)
Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
干预措施: Placebo
Placebo/Amlodipine/ISMN ER (Sequence 5)
Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
干预措施: Placebo
Amlodipine/ISMN ER/Placebo (Sequence 6)
Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule for 4 weeks during Period, with a 2-week washout between each period.
干预措施: Placebo
结局指标
主要结局
Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment
时间窗: Baseline (0 hrs), 12 hours post-dose (Day 1)
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Single dose effects on AIx were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment
时间窗: Baseline (0 hrs), 24 hours after the Day 28 dose
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment
时间窗: Baseline (0 hrs), 12 hours post-dose (Day 1)
Central SBP was measured by the SphygmoCor® device. Single dose effects on central SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment
时间窗: Baseline (0 hrs), 24 hours after the Day 28 dose
Central SBP was measured by the SphygmoCor® device. Central SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment
时间窗: Baseline (0 hrs), 24 hours after the Day 28 dose
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment
时间窗: Baseline (0 hrs), 12 hours post-dose (Day 1)
Central DBP was measured by the SphygmoCor® device. Single dose effects on central DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment
时间窗: Baseline (0 hrs), 24 hours after the Day 28 dose
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment
时间窗: Baseline (0 hrs), 24 hours after the Day 28 dose
Central DBP was measured by the SphygmoCor® device. Central DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment
时间窗: Baseline (0 hrs), 12 hours post-dose (Day 1)
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment
时间窗: Baseline (0 hrs), 12 hours post-dose (Day 1)
Peripheral DBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.