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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01615198
First received: June 6, 2012
Last updated: July 20, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Essential Hypertension
Drug: Olmesartan
Drug: Placebo
Drug: LCZ696
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, 4 weeks, 14 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Baseline in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mean Sitting Pulse Pressure [ Time Frame: Baseline, 4 weeks, 10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    Pulse rate was with automated BP device after the 4th blood pressure measurement at each visit.

  • Change From Baseline in Daytime and Nighttime maSBP/maDBP [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in maSBP and maDBP Lowering Based on Nocturnal BP Dipping (Dipper Versus Non-dipper) in Dippers [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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 chnage from baseline indicates improvement.

  • Change From Baseline in maSBP and maDBP Lowering Based on Nocturnal BP Dipping (Dipper Versus Non-dipper) Status in Non-dippers [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    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 chnage from baseline indicates improvement.

  • Number of Participants Achieving Overall Blood Pressure Control in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: 4 weeks, 10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg.

  • Number of Participants Achieving Successful Response in msSBP and msDBP [ Time Frame: 4 weeks,10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]
    Adverse event monitoring was conducted throughout the study.


Enrollment: 588
Study Start Date: August 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Olmesartan
10 mg, 20 mg, 40 mg capsules
Drug: Placebo
Matching placebo of LCZ696 tablet, matching placebo of Olmesartan capsule

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01615198

  Hide Study Locations
Locations
China, Chongqing
Novartis Investigative Site
Chongqing, Chongqing, China, 400042
China, Hunan
Novartis Investigative Site
Changsha, Hunan, China, 410003
China, Jiangsu
Novartis Investigative Site
Suzhou, Jiangsu, China, 215006
China, Liaoning
Novartis Investigative Site
Shenyang, Liaoning, China, 110003
China, Shanxi
Novartis Investigative Site
Xi'an, Shanxi, China, 710061
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310006
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310013
China
Novartis Investigative Site
Beijing, China, 100044
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Beijing, China, 100020
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Shanghai, China, 200025
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Tianjin, China, 300142
Hong Kong
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Hong Kong, Shatin, NT, Hong Kong
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Hong Kong, Hong Kong
Japan
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Toon-city, Ehime, Japan, 791-0295
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Chikushi-gun, Fukuoka, Japan, 811-1244
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Fukuoka-city, Fukuoka, Japan, 810-0066
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Kitakyushu-city, Fukuoka, Japan, 807-0856
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Asahikawa, Hokkaido, Japan, 078-8214
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Sapporo, Hokkaido, Japan, 003-0026
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Sapporo, Hokkaido, Japan, 003-0825
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Sapporo-city, Hokkaido, Japan, 062-0053
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Sapporo-city, Hokkaido, Japan, 063-0842
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Kawasaki-city, Kanagawa, Japan, 210-0852
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Kyotanabe-city, Kyoto, Japan, 610-0361
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Kyoto-city, Kyoto, Japan, 615-8125
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Suita-city, Osaka, Japan, 565-0871
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Toyonaka-city, Osaka, Japan, 560-0082
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Fujimino, Saitama, Japan, 356-0053
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Hiki-Gun, Saitama, Japan, 355-0328
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Koshigaya city, Saitama, Japan, 343-0826
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Tokorozawa-city, Saitama, Japan, 359-1161
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Edogawa-ku, Tokyo, Japan, 133-0061
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Edogawa-ku, Tokyo, Japan, 134-0084
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Hachioji, Tokyo, Japan, 192-0046
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Hachioji-city, Tokyo, Japan, 192-0918
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Katsushika-ku, Tokyo, Japan, 124-0024
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Kiyose-city, Tokyo, Japan, 204-0021
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Kunitachi, Tokyo, Japan, 186-0001
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Meguro-ku, Tokyo, Japan, 152-0031
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Minato-ku, Tokyo, Japan, 105-7390
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Minato-ku, Tokyo, Japan, 108-0075
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Shibuya-ku, Tokyo, Japan, 150-0002
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Shinagawa-ku, Tokyo, Japan, 141-0032
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Tachikawa, Tokyo, Japan, 190-0013
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Taito, Tokyo, Japan, 111-0052
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Toshima-ku, Tokyo, Japan, 171-0021
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Osaka, Japan, 560-0005
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Saitama, Japan, 337-0012
Korea, Republic of
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Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
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Goyang, Gyeonggi-do, Korea, Republic of, 412-270
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Jeonju-si, Jeollabuk-do, Korea, Republic of, 561-712
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Koyang, Kyunggi, Korea, Republic of, 410-719
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Bundang, Seongnam, Korea, Republic of, 463-707
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Daegu, Korea, Republic of, 700-712
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Daejeon, Korea, Republic of, 302-241
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Incheon, Korea, Republic of, 400-711
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Incheon, Korea, Republic of, 403-720
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Seoul, Korea, Republic of, 135-720
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Seoul, Korea, Republic of, 152-703
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Seoul, Korea, Republic of, 100-380
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Seoul, Korea, Republic of, 150-713
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Seoul, Korea, Republic of, 150-950
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Seoul, Korea, Republic of, 134-727
Philippines
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Quezon City, Manila, Philippines, 1100
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Manila, Metro Manila, Philippines, 1000
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Quezon City, Philippines, 1102
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Quezon City, Philippines, 1100
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Valenzuela City, Philippines, 1441
Taiwan
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Taichung, Taiwan ROC, Taiwan, 40201
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Taipei, Taiwan, ROC, Taiwan, 112
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Changhua, Taiwan, 500
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Kaohsiung, Taiwan, 807
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Taichung, Taiwan, 40447
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Taipei, Taiwan
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Taipei, Taiwan, 114
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Taipei, Taiwan, 10002
Thailand
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Bangkok, Thailand, 10400
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01615198     History of Changes
Other Study ID Numbers: CLCZ696A2316
Study First Received: June 6, 2012
Results First Received: July 20, 2015
Last Updated: July 20, 2015
Health Authority: China: Food and Drug Administration
Korea: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency, Ministry of Health, Labor and Welfare
Taiwan: Department of Health
Thailand: Ministry of Public Health
Hong Kong: Department of Health
Philippines: Department of Health

Keywords provided by Novartis:
Hypertension, blood pressure, LCZ696, dual inhibitor, neprilysin, NEP inhibition, vasopeptidase, ARNi, angiotensin receptor

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Olmesartan
Olmesartan medoxomil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015