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

A 14 Week, Randomized, Double-blind, Multi-center, Parallel Group, Active Controlled Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Elderly Patients With Essential Hypertension

The purpose of this study is to access the efficacy and safety of LCZ696 compared to olmesartan in elderly Asian patients for the treatment of hypertension.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 588
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100020
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300142
    • Novartis Investigative Site
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410003
      • Novartis Investigative Site
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Novartis Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110003
      • Novartis Investigative Site
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310013
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Shatin, NT
    • Hong Kong, Shatin, NT, Hong Kong
      • Novartis Investigative Site
• Japan
  • Osaka, Japan, 560-0005
    • Novartis Investigative Site
  • Saitama, Japan, 337-0012
    • Novartis Investigative Site
  • Ehime
    • Toon-city, Ehime, Japan, 791-0295
      • Novartis Investigative Site
  • Fukuoka
    • Chikushi-gun, Fukuoka, Japan, 811-1244
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 810-0066
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 807-0856
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8214
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 003-0026
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 003-0825
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 062-0053
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 063-0842
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 210-0852
      • Novartis Investigative Site
  • Kyoto
    • Kyotanabe-city, Kyoto, Japan, 610-0361
      • Novartis Investigative Site
    • Kyoto-city, Kyoto, Japan, 615-8125
      • Novartis Investigative Site
  • Osaka
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
    • Toyonaka-city, Osaka, Japan, 560-0082
      • Novartis Investigative Site
  • Saitama
    • Fujimino, Saitama, Japan, 356-0053
      • Novartis Investigative Site
    • Hiki-Gun, Saitama, Japan, 355-0328
      • Novartis Investigative Site
    • Koshigaya city, Saitama, Japan, 343-0826
      • Novartis Investigative Site
    • Tokorozawa-city, Saitama, Japan, 359-1161
      • Novartis Investigative Site
  • Tokyo
    • Edogawa-ku, Tokyo, Japan, 133-0061
      • Novartis Investigative Site
    • Edogawa-ku, Tokyo, Japan, 134-0084
      • Novartis Investigative Site
    • Hachioji, Tokyo, Japan, 192-0046
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Katsushika-ku, Tokyo, Japan, 124-0024
      • Novartis Investigative Site
    • Kiyose-city, Tokyo, Japan, 204-0021
      • Novartis Investigative Site
    • Kunitachi, Tokyo, Japan, 186-0001
      • Novartis Investigative Site
    • Meguro-ku, Tokyo, Japan, 152-0031
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-7390
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Novartis Investigative Site
    • Shibuya-ku, Tokyo, Japan, 150-0002
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-0032
      • Novartis Investigative Site
    • Tachikawa, Tokyo, Japan, 190-0013
      • Novartis Investigative Site
    • Taito, Tokyo, Japan, 111-0052
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0021
      • Novartis Investigative Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
    • Novartis Investigative Site
  • Daejeon, Korea, Republic of, 302-241
    • Novartis Investigative Site
  • Incheon, Korea, Republic of, 22332
    • Novartis Investigative Site
  • Incheon, Korea, Republic of, 403-720
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 150-713
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 150-950
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 152-703
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 135-720
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 100-380
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 134-727
    • Novartis Investigative Site
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Novartis Investigative Site
  • Gyeonggi-do
    • Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
      • Novartis Investigative Site
    • Goyang, Gyeonggi-do, Korea, Republic of, 412-270
      • Novartis Investigative Site
  • Jeollabuk-do
    • Jeonju-si, Jeollabuk-do, Korea, Republic of, 561-712
      • Novartis Investigative Site
  • Kyunggi
    • Koyang, Kyunggi, Korea, Republic of, 410-719
      • Novartis Investigative Site
• Philippines
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Valenzuela City, Philippines, 1441
    • Novartis Investigative Site
  • Manila
    • Quezon City, Manila, Philippines, 1100
      • Novartis Investigative Site
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1000
      • Novartis Investigative Site
• Taiwan
  • Changhua, Taiwan, 500
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan
    • Novartis Investigative Site
  • Taipei, Taiwan, 114
    • Novartis Investigative Site
  • Taiwan ROC
    • Taichung, Taiwan ROC, Taiwan, 40201
      • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must give written informed consent before any assessment is performed
• Patients with essential hypertension, untreated or currently taking antihypertensive therapy must have a mean sitting systolic blood pressure ≥ 150 mmHg and < 180 mmHg
• Patients must be able to communicate and comply with all study requirements and demonstrate good medication compliance

Exclusion criteria:

• Patients with severe hypertension (msDBP ≥ 110 mmHg and/or msSBP ≥180 mmHg). Patients with history of angioedema, drug-related or otherwise
• Patients with history or evidence of a secondary form of hypertension
• Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke
• History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1.
• Current angina pectoris requiring medication (other than patients on a stable dose of oral or topical nitrates).
• Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled and are not on a stable dose of antidiabetic medication
• Patients with previous or current diagnosis of heart failure (NYHA Class II-IV).
• Patients with a clinically significant valvular heart disease at the time of screening
• Women of child-bearing potential, who do not use adequate birth control methods 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696; Participants were treated with one LCZ696 100 mg tablet and one placebo of LCZ696 every day (qd) for 4 weeks along with placebo of Olmesartan 10 mg capsule qd. Participants were then up-titrated to LCZ 200 mg tablet and one placebo of LCZ696 qd for 6 weeks along with placebo of Olmesartan 20 mg capsule qd. Participants, who did not achieve their goal BP, were uptitrated to 2 LCZ696 200 mg tablets (LCZ696 400 mg) qd for 4 weeks along with placebo of Olmesartan 40 mg capsule qd.	Drug: Placebo; Matching placebo of LCZ696 tablet, matching placebo of Olmesartan capsule; Drug: LCZ696; 100 mg, 200 mg tablets
Active Comparator: Olmesartan; Participants were treated with olmesartan 10 mg qd for 4 weeks along with 2 placebo of LCZ696 tablets qd. Participants were then uptitrated to olmesartan 20 mg qd for 6 weeks along with 2 placebo of LCZ696 tablets qd. Participants, who did not achieve their goal BP, were uptitrated to olmesartan 40 mg qd for the remaining 4 weeks and 2 placebo LCZ696 tablets qd.	Drug: Placebo; Matching placebo of LCZ696 tablet, matching placebo of Olmesartan capsule; Drug: Olmesartan; 10 mg, 20 mg, 40 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Sitting BP measurements were performed at trough (immediately prior to dosing at the clinic). At study entry, BP was measured in both arms. The arm with the higher SBP reading was used for the 4 measurements at screening visit and the same arm was used at all subsequent visits. A negative change from baseline indicates improvement.	Baseline, 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP)	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. Readings were taken every 20 minutes over the 24 hour period in the non-dominant arm. A negative change from baseline indicates improvement.	Baseline, 10 weeks
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP)	Sitting BP measurements were performed at trough (immediately prior to dosing at the clinic). At study entry, BP was measured in both arms. The arm with the higher SBP reading was used for the 4 measurements at screening visit and the same arm was used at all subsequent visits. A negative change from baseline indicated improvement.	Baseline, 4 weeks, 14 weeks
Change in Baseline in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP)	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. Readings were taken every 20 minutes over the 24 hour period in the non-dominant arm. A negative change from baseline indicates improvement.	Baseline, 10 weeks
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Sitting BP measurements was performed at trough (immediately prior to dosing at the clinic). At study entry, BP was measured in both arms. The arm with the higher SBP reading was used for the 4 measurements at screening visit and the same arm was used at all subsequent visits. A negative change from baseline indicates improvement.	Baseline, 10 weeks
Change From Baseline in Mean Sitting Pulse Pressure	Pulse rate was with automated BP device after the 4th blood pressure measurement at each visit.	Baseline, 4 weeks, 10 weeks, 14 weeks
Change From Baseline in Daytime and Nighttime maSBP/maDBP	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. Readings were taken every 20 minutes over the 24 hour period in the non-dominant arm. A negative change from baseline indicates improvement.	Baseline, 10 weeks
Change From Baseline in maSBP and maDBP Lowering Based on Nocturnal BP Dipping (Dipper Versus Non-dipper) in Dippers	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. Readings were taken every 20 minutes over the 24 hour period in the non-dominant arm. A non-dipper was defined as a participant who, at baseline, had a mean nighttime ABPM (10 pm - 6 am) that did not drop ≥ 10% below his or her mean daytime ABPM (6 am - 10 pm). A negative change from baseline indicates improvement.	Baseline, 10 weeks
Change From Baseline in maSBP and maDBP Lowering Based on Nocturnal BP Dipping (Dipper Versus Non-dipper) Status in Non-dippers	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. Readings were taken every 20 minutes over the 24 hour period in the non-dominant arm. A non-dipper was defined as a participant who, at baseline, had a mean nighttime ABPM (10 pm - 6 am) that did not drop ≥ 10% below his or her mean daytime ABPM (6 am - 10 pm). A negative change from baseline indicates improvement.	Baseline, 10 weeks
Number of Participants Achieving Overall Blood Pressure Control in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP)	A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg.	4 weeks, 10 weeks, 14 weeks
Number of Participants Achieving Successful Response in msSBP and msDBP	Blood pressure response in msSBP was defined as a mean sitting BP < 140 mmHg or a >=20 mmHg reduction from baseline. Blood pressure response in msDBP was defined as a mean sitting diastolic blood pressure, 90 mmHg or >=10 mmHg reduction from baseline.	4 weeks,10 weeks, 14 weeks
Number of Participants With Adverse Events, Serious Adverse Events and Death	Adverse event monitoring was conducted throughout the study.	14 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 8, 2012

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension, blood pressure, LCZ696, dual inhibitor, neprilysin, NEP inhibition, vasopeptidase, ARNi, angiotensin receptor
• 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; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A2316