Clinical trial NCT01865188: Study of the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hypertension
Keywords: LCZ696,
amlodipine,
hypertension,
ABPM
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-05-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the blood pressure lowering effect and safety of LCZ696 when given alone and in combination with amlodipine in patients with essential hypertension.


Eligibility criteria: Inclusion Criteria:

1. Male or female outpatients
2. Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy
3. 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.
4. 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.
5. Patients must have an absolute difference of ≤15 mmHg in msSBP between the randomization visit and the preceding visit.
6. 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:

1. Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
2. History of angioedema, drug-related or otherwise
3. 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
4. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke
5. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1
6. Pregnant or lactating women
7. Women of child-bearing potential not using highly effective methods of contraception Other protocol defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone.
timeFrame: baseline, 8 weeks
Secondary outcomes:
measure: Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
timeFrame: baseline, 8 weeks
measure: Change from baseline in pulse pressure
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
timeFrame: baseline, 8 weeks
measure: Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
timeFrame: baseline, 8 weeks
measure: 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
timeFrame: baseline, 8 weeks
measure: 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
timeFrame: baseline, 8 weeks
measure: 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
timeFrame: baseline, 8 weeks
measure: 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
timeFrame: baseline, 8 weeks
measure: Percentage of patients achieving msSBP <140 mmHg and msDBP <90 mmHg
timeFrame: 8 weeks
measure: Percentage of patients achieving msSBP <140 mmHg or a reduction ≥20 mmHg from baseline
timeFrame: Baseline, 8 weeks
measure: Percentage of patients achieving msDBP <90 mmHg or a reduction ≥10 mmHg from baseline
timeFrame: Baseline, 8 weeks
measure: Number of patients reporting adverse events
timeFrame: 8 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: