Study of the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Hypertension

Novartis

Status and phase: Withdrawn; Phase 3

Conditions: Hypertension

Treatments: Drug: LCZ696; Drug: Placebo; Drug: LCZ696 and amlodipine combination; Drug: Amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01865188

2013-001643-30 (EudraCT Number)

CLCZ696A2320

Details and patient eligibility

About

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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 9 patient groups, including a placebo group

LCZ696 200 mg

Experimental group

Description:

Patients randomized to this treatment arm will receive LCZ696 200 mg once daily for 8 weeks.

Treatment:

Drug: LCZ696

LCZ696 400 mg

Experimental group

Description:

Patients randomized to this treatment arm will receive LCZ696 400 mg once daily for 8 weeks.

Treatment:

Drug: LCZ696

Amlodipine 5 mg

Active Comparator group

Description:

Patients randomized to this treatment arm will receive amlodipine 5 mg once daily for 8 weeks.

Treatment:

Drug: Amlodipine

Amlodipine 10 mg

Active Comparator group

Description:

Patients randomized to this treatment arm will receive amlodipine 10 mg once daily for 8 weeks.

Treatment:

Drug: Amlodipine

LCZ696 200 mg and amlodipine 5 mg

Experimental group

Description:

Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 8 weeks.

Treatment:

Drug: LCZ696 and amlodipine combination

LCZ696 200 mg and amlodipine 10 mg

Experimental group

Description:

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.

Treatment:

Drug: LCZ696 and amlodipine combination

LCZ696 400 mg and amlodipine 5 mg

Experimental group

Description:

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.

Treatment:

Drug: LCZ696 and amlodipine combination

LCZ696 400 mg and amlodipine 10 mg

Experimental group

Description:

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.

Treatment:

Drug: LCZ696 and amlodipine combination

Placebo

Placebo Comparator group

Description:

Patients randomized to this treatment arm will receive placebo once daily for 8 weeks.

Treatment:

Drug: Placebo