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

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

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

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: LCZ696; Drug: Placebo of LCZ696; Drug: Placebo of Olmesartan; Drug: Olmesartan

• Study Type: Interventional
• Enrollment (Actual): 1438
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100029
    • Novartis Investigative Site
  • Beijing, China, 100020
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Fuzhou, China, 350001
    • Novartis Investigative Site
  • Shanghai, China, 200031
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300142
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100044
      • Novartis Investigative Site
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Novartis Investigative Site
    • Chongqing, Chongqing, China, 400042
      • Novartis Investigative Site
  • Fujian
    • Fuzhou, Fujian, China
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Novartis Investigative Site
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Novartis Investigative Site
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410003
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Novartis Investigative Site
    • Suzhou, Jiangsu, China, 215006
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novartis Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • Novartis Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Novartis Investigative Site
    • Shanghai, Shanghai, China, 200072
      • Novartis Investigative Site
  • Shanxi
    • Xi'an, Shanxi, China, 710004
      • Novartis Investigative Site
    • Xi'an, Shanxi, China, 710061
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300121
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310013
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 06591
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 08308
      • Novartis Investigative Site
  • Kyunggi
    • Koyang, Kyunggi, Korea, Republic of, 410-719
      • Novartis Investigative Site
• Philippines
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Manila
    • Quezon City, Manila, Philippines, 1100
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169609
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 82445
    • Novartis Investigative Site
  • New Taipei City, Taiwan, 23561
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 110
    • Novartis Investigative Site
  • Taipei County, Taiwan, 22060
    • Novartis Investigative Site
  • Yun-Lin, Taiwan, 640
    • Novartis Investigative Site
  • Taiwan ROC
    • Tainan 704, Taiwan ROC, Taiwan, 70403
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Rajathevee, Thailand, 10400
    • Novartis Investigative Site
  • THA
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696 200 mg; Patients 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.	Drug: LCZ696; LCZ696 200 mg tablet; Drug: Placebo of LCZ696; Placebo tablet of LCZ696 200 mg once daily; Drug: Placebo of Olmesartan; Placebo capsule of olmesartan 20 mg once daily
Experimental: LCZ696 400 mg; Patients 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.	Drug: LCZ696; LCZ696 200 mg tablet; Drug: Placebo of LCZ696; Placebo tablet of LCZ696 200 mg once daily; Drug: Placebo of Olmesartan; Placebo capsule of olmesartan 20 mg once daily
Active Comparator: Olmesartan 20 mg; Patients will be treated with Olmesartan 20 mg for eight weeks once daily along with placebo of LCZ696 tablets once daily.	Drug: Placebo of LCZ696; Placebo tablet of LCZ696 200 mg once daily; Drug: Olmesartan; Olmesartan 20 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
Number of Patients Achieving Successful Blood Pressure Control	Successful blood pressure control is defined as msSBP <140 mmHg and msDBP <90 mmHg.	8 weeks
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 5, 2013
• First Posted (Estimate): February 7, 2013

Study Record Updates

• Last Update Posted (Estimate): December 29, 2016
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Essential hypertension; LCZ696
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan; Olmesartan Medoxomil; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A2315 (Other Identifier: Novartis)