Study of the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Hypertension
2014年8月4日 更新者：Novartis Pharmaceuticals
An 8-week Randomized, Double-blind, Placebo-controlled Factorial Study to Evaluate the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Essential Hypertension
To evaluate the blood pressure lowering effect and safety of LCZ696 when given alone and in combination with amlodipine in patients with essential hypertension.
研究概览
研究类型
介入性
阶段
- 第三阶段
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Male or female outpatients
- Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy
- Treated patients (using antihypertensive treatments within 4 weeks prior to Visit 1) must have an msSBP ≥150 mmHg and <180 mmHg at the randomization visit and msSBP ≥140 mmHg <180 mmHg at the preceding visit.
- Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP ≥150 mmHg and <180 mmHg at both the randomization visit and the preceding visit.
- Patients must have an absolute difference of ≤15 mmHg in msSBP between the randomization visit and the preceding visit.
- Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the treatment run-in period.
Exclusion Criteria:
- Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
- History of angioedema, drug-related or otherwise
- History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension
- Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke
- History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1
- Pregnant or lactating women
- Women of child-bearing potential not using highly effective methods of contraception Other protocol defined inclusion/exclusion criteria may apply
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：LCZ696 200 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg once daily for 8 weeks.
|
Experimental monotherapy doses
|
|
实验性的：LCZ696 400 mg
Patients randomized to this treatment arm will receive LCZ696 400 mg once daily for 8 weeks.
|
Experimental monotherapy doses
|
|
有源比较器：Amlodipine 5 mg
Patients randomized to this treatment arm will receive amlodipine 5 mg once daily for 8 weeks.
|
Active comparator monotherapy doses
|
|
有源比较器：Amlodipine 10 mg
Patients randomized to this treatment arm will receive amlodipine 10 mg once daily for 8 weeks.
|
Active comparator monotherapy doses
|
|
实验性的：LCZ696 200 mg and amlodipine 5 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 8 weeks.
|
Experimental combination doses
|
|
实验性的：LCZ696 200 mg and amlodipine 10 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 200 mg and amlodipine 10 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
实验性的：LCZ696 400 mg and amlodipine 5 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 5 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
实验性的：LCZ696 400 mg and amlodipine 10 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 10 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
安慰剂比较：Placebo
Patients randomized to this treatment arm will receive placebo once daily for 8 weeks.
|
Placebo comparator dose
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
At the first study visit, blood pressure will be measured in both arms and the arm with highest sitting SBP will be found and used for all subsequent readings throughout the study.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone.
大体时间：baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.
|
baseline, 8 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in pulse pressure
大体时间：baseline, 8 weeks
|
Pulse pressure will be calculated as the difference between msSBP and msDBP for both office BP and ABPM.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure will be calculated using the systolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum systolic blood pressure effect found in the hours after dosing.
|
baseline, 8 weeks
|
|
Change from baseline in trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
大体时间：baseline, 8 weeks
|
The trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure will be calculated using the diastolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum diastolic blood pressure effect found in the hours after dosing.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
大体时间：baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Percentage of patients achieving msSBP <140 mmHg and msDBP <90 mmHg
大体时间：8 weeks
|
The percentage of patients achieving blood pressure control (msSBP <140 mmHg and msDBP <90 mmHg) after 8 weeks of treatment will be calculated.
|
8 weeks
|
|
Percentage of patients achieving msSBP <140 mmHg or a reduction ≥20 mmHg from baseline
大体时间：Baseline, 8 weeks
|
The percentage of patients achieving a successful response in msSBP (msSBP <140 mmHg or a reduction ≥20 mmHg from baseline) after 8 weeks of treatment will be calculated.
|
Baseline, 8 weeks
|
|
Percentage of patients achieving msDBP <90 mmHg or a reduction ≥10 mmHg from baseline
大体时间：Baseline, 8 weeks
|
The percentage of patients achieving a successful response in msSBP (msDBP <90 mmHg or a reduction ≥10 mmHg from baseline) after 8 weeks of treatment will be calculated.
|
Baseline, 8 weeks
|
|
Number of patients reporting adverse events
大体时间：8 weeks
|
As an assessment of safety of monotherapy and combination therapy of LCZ696, total adverse events, serious adverse events and deaths after 8 weeks of treatment will be reported .
|
8 weeks
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2014年4月1日
初级完成 (预期的)
2015年4月1日
研究完成 (预期的)
2015年4月1日
研究注册日期
首次提交
2013年5月24日
首先提交符合 QC 标准的
2013年5月24日
首次发布 (估计)
2013年5月30日
研究记录更新
最后更新发布 (估计)
2014年8月5日
上次提交的符合 QC 标准的更新
2014年8月4日
最后验证
2014年8月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
LCZ696的临床试验
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University Hospital, Montpellier完全的
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Novartis Pharmaceuticals完全的
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Novartis Pharmaceuticals完全的射血分数降低的慢性心力衰竭比利时, 爱沙尼亚, 丹麦, 希腊, 英国, 德国, 拉脱维亚, 立陶宛, 西班牙, 荷兰, 保加利亚, 芬兰, 波兰, 捷克语, 冰岛, 瑞典, 法国, 爱尔兰, 挪威
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Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI)完全的
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Novartis Pharmaceuticals完全的