Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Japanese Patients With Essential Hypertension

Phase 3

Completed

Conditions: Essential Hypertension

Interventions: Drug: LCZ696
Drug: Olmesartan
Drug: Placebo

Registration Number: NCT01599104

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study assessed the efficacy of LCZ696 in Japanese patients with essential hypertension

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1161

Inclusion Criteria

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 (Visit 201) and msSBP ≥140 mmHg < 180 mmHg at the visit immediately proceeding Visit 201 (Visit 102 or 103).
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 Visit 1 and Visit 201.
Patients must have an absolute difference of ≤15 mmHg in msSBP between Visit 201 and the immediately preceding visit;

Exclusion Criteria

Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).
History of angioedema, drug-related or otherwise, as reported by the patient.
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.
Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch.

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCZ696 200 mg	LCZ696	LCZ696 200 mg tablet and placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) tablet once daily for 8 weeks
Olmesartan 20 mg	Placebo	Olmesartan 20 mg capsule and placebo to LCZ696 (2 tablets) once daily for 8 weeks
LCZ696 200 mg	Placebo	LCZ696 200 mg tablet and placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) tablet once daily for 8 weeks
LCZ696 400 mg	LCZ696	LCZ696 200 mg tablet and a placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) once daily for one week; then up-titrated to LCZ696 400 mg and placebo to Olmesartan (1 capsule) once daily for the remaining 7 weeks
LCZ696 400 mg	Placebo	LCZ696 200 mg tablet and a placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) once daily for one week; then up-titrated to LCZ696 400 mg and placebo to Olmesartan (1 capsule) once daily for the remaining 7 weeks
Olmesartan 20 mg	Olmesartan	Olmesartan 20 mg capsule and placebo to LCZ696 (2 tablets) once daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Baseline, 8 weeks	Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean 24-hour Ambulatory SBP (maSBP) at Week 8	Baseline, 8 weeks	Ambulatory blood pressure monitoring (ABPM) over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Baseline, 8 weeks	Sitting BP measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.
Percentage of Participants Achieving a Successful Response in Overall Blood Pressure Control at Week 8	8 weeks	A successful response in overall BP control rate was defined as msSBP \< 140 mmHg and msDBP \<90 mmHg.
Percentage of Participants Achieving a Successful msSBP Response	8 weeks	Successful msSBP response was defined as \< 140 mmHg or ≥ 20 mmHg reduction from baseline.
Change From Baseline in maSBP and maDBP for Daytime/Nighttime	Baseline, 8 weeks	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Percentage of Participants Achieving a Successful msDBP Response	8 weeks	Successfull msDBP response was defined as \<90 mmHg or ≥10 mmHg reduction from baseline.
Change From Baseline in Mean 24-hour Ambulatory DBP (maDBP) at Week 8	Baseline, 8 weeks	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure	Baseline, 8 weeks	Ambulatory pulse pressure was calculated as hourly ambulatory SBP minus hourly ambulatory DBP in a subset of participants.
Number of Patients With Adverse Events, Serious Adverse Events and Death	8 weeks	Participants were monitored for adverse events, serious adverse events and deaths throughout the study.
Change From Baseline in Office Pulse Pressure	Baseline, 8 weeks	Office pulse pressure was calculated as msSBP minus msDBP. Sitting blood pressure (BP) measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and then averaged to calculate the mean BP value. The baseline PP value was subtracted from the week 8 PP value to determine the change from baseline in PP.