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

Phase 3
Completed
Conditions
Essential Hypertension
Interventions
Registration Number
NCT01785472
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study will assess the efficacy and safety of multiple doses of LCZ696 compared to olmesartan in Asian patients with essential hypertension

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1438
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 preceding 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
  • Patients with 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
GroupInterventionDescription
LCZ696 200 mgLCZ696Patients will be treated with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily(qd) for eight weeks along with placebo of Olmesartan 20 mg capsule once daily.
LCZ696 200 mgPlacebo of LCZ696Patients will be treated with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily(qd) for eight weeks along with placebo of Olmesartan 20 mg capsule once daily.
LCZ696 200 mgPlacebo of OlmesartanPatients will be treated with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily(qd) for eight weeks along with placebo of Olmesartan 20 mg capsule once daily.
LCZ696 400 mgLCZ696Patients will start with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily (qd) for one week, thereafter all patients in the treatment group will be up-titrated to two LCZ696 200 mg tablets (400 mg of LCZ696) qd for the remaining seven weeks. Placebo of Olmesartan 20 mg capsule once daily also will be taken.
LCZ696 400 mgPlacebo of LCZ696Patients will start with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily (qd) for one week, thereafter all patients in the treatment group will be up-titrated to two LCZ696 200 mg tablets (400 mg of LCZ696) qd for the remaining seven weeks. Placebo of Olmesartan 20 mg capsule once daily also will be taken.
LCZ696 400 mgPlacebo of OlmesartanPatients will start with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily (qd) for one week, thereafter all patients in the treatment group will be up-titrated to two LCZ696 200 mg tablets (400 mg of LCZ696) qd for the remaining seven weeks. Placebo of Olmesartan 20 mg capsule once daily also will be taken.
Olmesartan 20 mgOlmesartanPatients will be treated with Olmesartan 20 mg for eight weeks once daily along with placebo of LCZ696 tablets once daily.
Olmesartan 20 mgPlacebo of LCZ696Patients will be treated with Olmesartan 20 mg for eight weeks once daily along with placebo of LCZ696 tablets once daily.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 200 mg Versus Olmesartan 20 mgbaseline, 8 weeks

Sitting BP measurements will be performed at screening through end of study at every visit. Four separate sitting BP measurements will be obtained with a full two minute interval between measurements.

Secondary Outcome Measures
NameTimeMethod
Number of Patients With Adverse Events, Serious Adverse Events, and Death as Assessment of Safety and Tolerabilitybaseline, 8 weeks

Participants were monitored for adverse events, serious adverse events and deaths throughout the study.

Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 400 mg Versus Olmesartan 20 mgbaseline, 8 weeks

Sitting BP measurements will be performed at screening through end of study at every visit. Four separate sitting BP measurements will be obtained with a full two minute interval between measurements

Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Dippers.baseline, 8 weeks

Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement

Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Non-dippers.baseline, 8 weeks

Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement

Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Between LCZ696 200, and LCZ696 400 mg Versus Olmesartan 20 mgbaseline, 8 weeks

Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement

Number of Patients Achieving Successful Blood Pressure Control8 weeks

Successful blood pressure control is defined as msSBP \<140 mmHg and msDBP \<90 mmHg.

Change From Baseline in Office Pulse Pressure (msPP)baseline, 8 weeks

Four separate sitting BP measurements should be obtained with a full two minute interval between measurements.

Change From Baseline in Mean 24-hour Ambulatory Blood Pressurebaseline, 8 weeks

In this analysis, mean 24 hour ambulatory systolic blood pressure maSBP, mean 24 hour ambulatory diastolic blood pressure maDBP, daytime and nightime maSBP and maDBP will be reported. Ambulatory blood pressure monitoring over a 24 hour period will be conducted at two time points during the study.

Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Dippers.baseline, 8 weeks

Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement

Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Non-dippers.baseline, 8 weeks

Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement

Change From Baseline in Ambulatory Pulse Pressurebaseline, 8 weeks

Ambulatory pulse pressure (PP) is calculated by hourly ambulatory SBP and hourly ambulatory DBP over a 24-hour period.

Number of Respondersbaseline, 8 weeks

Responders are patients with msSBP response (\<140 mmHg or ≥20 mmHg reduction from baseline) and msDBP response (\<90 mmHg or ≥10 mmHg reduction from baseline)

Trial Locations

Locations (1)

Novartis Investigative Site

🇹🇭

Rajathevee, Thailand

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