Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

Phase 2

Completed

Conditions: Hypertension

Interventions: Drug: LCZ696
Drug: AHU377
Drug: Valsartan
Drug: Placebo

Registration Number: NCT00549770

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1334

Inclusion Criteria

Male or females from 18 up to and including 75 years
Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs)
Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2).
Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP> 95 mmHg at baseline (Visit 3);

Exclusion Criteria

Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg)
History of angioedema, drug-related or otherwise, as reported by the patient
Type 1 or Type 2 diabetes mellitus (according to the ADA criteria)
History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc.
History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCZ696 200 mg	LCZ696	Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 320 mg	Placebo	Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 100 mg	Placebo	Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
AHU377 200 mg	Placebo	Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Valsartan 80 mg	Placebo	Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 160 mg	Placebo	Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 100 mg	LCZ696	Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 400 mg	LCZ696	Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Placebo	Placebo	Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 200 mg	Placebo	Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 400 mg	Placebo	Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
AHU377 200 mg	AHU377	Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Valsartan 80 mg	Valsartan	Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 160 mg	Valsartan	Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 320 mg	Valsartan	Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	baseline, week 8	Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Successful Control in msSBP	8 weeks	Successful control in msSBP is defined as \<140 mmHg.
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	baseline, week 8	Sitting BP measurements were performed at screening through the end of the study at every study visit.
Change From Baseline in Nighttime maDBP and maSBP	baseline, 8 weeks	Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Nighttime mean SBP and DBP were the averages of the hourly means between 10 pm and 6 am.
Percentage of Participants Who Achieved a Successful Response in msDBP	8 weeks	Successful response in msDBP is defined as msDBP \<90 mmHg or a reduction ≥ 10 mmHg from baseline.
Change From Baseline in Daytime maDBP and maSBP	baseline, 8 weeks	Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the avergae of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm.
Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP	baseline, 8 weeks	Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8.
Percentage of Participants Who Achieved Successful Control in msDBP	8 weeks	Successful control in msDBP is defined as msDBP \<90 mmHg.
Percentage of Participants Who Achieved a Successful Response in msSBP	8 weeks	Successful response in msSBP is defined as msSBP \<140 mmHg or a reduction ≥ 20 mmHg from baseline.