A Multi-center, Double-blind, Double-dummy, Randomized, Placebo- and Active-reference, Parallel Group, Phase 2, Dose-finding Study With ACT-132577 in Subjects With Essential Hypertension (Grade 1 and 2).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,659
- 试验地点
- 86
- 主要终点
- Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
研究概览
简要总结
The main objective will be to evaluate the dose-response of ACT-132577 (aprocitentan) on diastolic blood pressure (DBP) in participants with grade 1 or 2 essential hypertension.
Secondary objectives will be to evaluate the dose-response of ACT-132577 on: systolic blood pressure (SBP); control and response rate of blood pressure; 24-hour ambulatory blood pressure monitoring (ABPM) and to evaluate the safety and tolerability of a once daily oral regimen of 4 doses of ACT-132577.
详细描述
Participation in the study is planned to last up to 18 weeks. A single-blind placebo run-in period of 4 to 6 weeks after which participants will be randomized into a double-blind treatment period of 8 weeks and a washout and follow-up period ending with an end-of-study visit approximately 12 weeks after randomization.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to any study-mandated procedure
- •No contra-indication to stop (according to label) anti-hypertensive treatment(s) at screening
- •Mild-to-moderate essential hypertension with or without ongoing anti-hypertensive treatment(s):
- •- Mean (of 5 measurements) sitting diastolic blood pressure (SiDBP) ≥ 90 to < 110 mmHg measured by office blood pressure measurements (OBPM).
- •Women of childbearing potential must have a negative pregnancy test and use of reliable methods of contraception
排除标准
- •Severe hypertension (grade 3): mean sitting systolic/diastolic BP (SiSBP/SiDBP; measured by OBPM) ≥ 180/110 mmHg, respectively.
- •Secondary hypertension
- •Known hypertensive retinopathy greater than Keith-Wagener Grade 2
- •Myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft within 12 months prior to randomization
- •Unstable angina within 6 months prior to randomization
- •Heart failure New York Heart Association class III and IV
- •Valvular defects (such as severe aortic or mitral valve disease) and/or hemodynamically relevant rhythm disturbances
- •Clinical evidence of cerebrovascular insufficiency or a cerebrovascular accident within 6 months prior to randomization.
- •Subjects working night shifts
- •Body mass index < 20 kg/m2 or > 40 kg/m2
- •Treatment with any medication which may affect BP (e.g., treatment of psychiatric diseases, ophthalmic preparations)
- •Treatment with strong cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors or inducers
- •Treatment with guanethidine and/or mineralocorticoid receptor antagonists within 1 month prior to Screening (Visit 1)
- •Treatment with another investigational treatment within 1 month prior to Screening (Visit 1)
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
研究组 & 干预措施
Placebo
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received placebo orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Placebo (Drug)
Aprocitentan 5 mg
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Aprocitentan 5 mg (Drug)
Aprocitentan 10 mg
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 10 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Aprocitentan 10 mg (Drug)
Aprocitentan 25 mg
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 25 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Aprocitentan 25 mg (Drug)
Aprocitentan 50 mg
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 50 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Aprocitentan 50 mg (Drug)
Lisinopril 20 mg
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received lisinopril 20 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
干预措施: Lisinopril 20 mg (Drug)
结局指标
主要结局
Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
时间窗: Baseline (Day 1) and end of double-blind treatment (Day 56)
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis. The absolute change in mean trough sitting diastolic blood pressure (SiDBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the diastolic blood pressure from the start of treatment.
次要结局
- Change From Baseline to End of Double-blind Treatment in Sitting Systolic Blood Pressure at Trough(Baseline (Day 1) and end of double-blind treatment (Day 56))
- Control Rates at the End of the Double-blind Treatment Period Based on Trough Sitting Diastolic and Systolic Blood Pressure(End of double-blind treatment (Day 56))
- Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Diastolic Blood Pressure(Baseline (Day 1) and end of double-blind treatment (Day 56))
- Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Systolic Blood Pressure(Baseline (Day 1) and end of double-blind treatment (Day 56))
- Change From Baseline to End of Double-blind Treatment in 24-hour Diastolic and Systolic Ambulatory Blood Pressure Monitoring (ABPM)(Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56))
- Ratio of Group Mean at Trough to Group Mean at Peak for Diastolic Blood Pressure Based on Ambulatory Blood Pressure Monitoring (ABPM)(Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56))