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

Essential Hypertension Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Active-controlled, 8-week Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Patients With Essential Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01785472
• Other study ID #: CLCZ696A2315
• Secondary ID: CLCZ696A2315
• Status: Completed
• Phase: Phase 3
• First received: February 5, 2013
• Last updated: August 6, 2015
• Start date: April 2013
• Est. completion date: August 2014

Study information

• Verified date: August 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1438
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• LCZ696
LCZ696 200 mg tablet
• Olmesartan
Olmesartan 20 mg capsule
• Placebo of LCZ696
Placebo tablet of LCZ696 200 mg once daily
• Placebo of Olmesartan
Placebo capsule of olmesartan 20 mg once daily

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Fuzhou
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanning	Guangxi
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xi'an	Shanxi
China	Novartis Investigative Site	Xi'an	Shanxi
Hong Kong	Novartis Investigative Site	Hong Kong
Korea, Republic of	Novartis Investigative Site	Koyang	Kyunggi
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Philippines	Novartis Investigative Site	Quezon City	Manila
Philippines	Novartis Investigative Site	Quezon City
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	New Taipei City
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan 704	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei County
Taiwan	Novartis Investigative Site	Yun-Lin
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen
Thailand	Novartis Investigative Site	Rajathevee

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Hong Kong,  Korea, Republic of,  Philippines,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 200 mg Versus Olmesartan 20 mg	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.	baseline, 8 weeks	No
Secondary	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 400 mg Versus Olmesartan 20 mg	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	baseline, 8 weeks	No
Secondary	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Between LCZ696 200, and LCZ696 400 mg Versus Olmesartan 20 mg	Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement	baseline, 8 weeks	No
Secondary	Change From Baseline in Office Pulse Pressure (msPP)	Four separate sitting BP measurements should be obtained with a full two minute interval between measurements.	baseline, 8 weeks	No
Secondary	Change From Baseline in Mean 24-hour Ambulatory Blood Pressure	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.	baseline, 8 weeks	No
Secondary	Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Dippers.	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	baseline, 8 weeks	No
Secondary	Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Dippers.	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	baseline, 8 weeks	No
Secondary	Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Non-dippers.	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	baseline, 8 weeks	No
Secondary	Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Non-dippers.	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	baseline, 8 weeks	No
Secondary	Percentage of Patients Achieving Successful Blood Pressure Control	Successful blood pressure control is defined as msSBP <140 mmHg and msDBP <90 mmHg.	8 weeks	No
Secondary	Change From Baseline in Ambulatory Pulse Pressure	Ambulatory pulse pressure (PP) is calculated by hourly ambulatory SBP and hourly ambulatory DBP over a 24-hour period.	baseline, 8 weeks	No
Secondary	Number of Responders	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)	baseline, 8 weeks	No
Secondary	Number of Patients With Adverse Events, Serious Adverse Events, and Death as Assessment of Safety and Tolerability	Participants were monitored for adverse events, serious adverse events and deaths throughout the study.	baseline, 8 weeks	Yes