Efficacy and Safety of LCZ696 Compared to Placebo in Patients With Essential Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01193101
First received: August 26, 2010
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

This study is a phase 2 study in patients with essential hypertension.


Condition Intervention Phase
Hypertension
Drug: LCZ696
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Placebo After 8 Weeks Treatment in 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 Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.


Secondary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.

  • Change From Baseline in 24 Hour Mean Ambulatory DBP and SBP [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the avergae of the readings taken in the corresponding post-dosing hour at randomization and at week 8. A negative change from baseline indicates improvement.

  • Change From Baseline in Daytime Mean Ambulatory DBP and SBP [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm. A negative change from baseline indicates improvement.

  • Change From Baseline in Nighttime Mean Ambulatory DBP and SBP [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Nighttime mean SBP and DBP were the averages of the hourly means between 10 pm and 6 am. A negative change from baseline indicates improvement.

  • Change From Baseline in Mean Sitting Pulse Pressure [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Mean sitting pulse pressure is the difference in msSBP and msDBP (msSBP - msDBP). A negative change from baseline indicates improvement.

  • Change From Baseline in Mean Ambulatory Pulse Pressure [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Mean ambulatory pulse pressure is the difference in maSBP and maDBP (maSBP - maDBP). A negative change from baseline indicates improvement.

  • Number of Participants Who Achieved a Successful Response in msDBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful response in msDBP is defined as msDBP <90 mmHg or a reduction ≥ 10 mmHg from baseline.

  • Number of Participants Who Achieved a Successful Response in msSBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful response in msSBP is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.

  • Number of Participants Who Achieved Successful BP Control [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    BP control is defined as BP < 140/90 mmHg.

  • Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Trough to post-dosing hour ratio at each post-dosing hour = [trough LSM of LCZ696 - trough LSM of placebo]/[post-dosing hour LSM of LCZ696 - post-dosing hour LSM of placebo]

  • Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Trough to post-dosing hour ratio at each post-dosing hour = [trough LSM of LCZ696 - trough LSM of placebo]/[post-dosing hour LSM of LCZ696 - post-dosing hour LSM of placebo]

  • Change From Week 8 to Week 9 in msDBP and msSBP After Single-blind Placebo Withdrawal at Week 8 [ Time Frame: 8 weeks, 9 weeks ] [ Designated as safety issue: No ]
    From week 8 to week 9, participants entered a single-blind placebo withdrawal period to assess the effect of LCZ696 on blood pressure following its discontinuation. Participants, who were randomized to the LCZ696 treatment groups, were discontinued from CLCZ696 at the end of week 8 and all 4 treatment groups received single-blind placebo for 1 week post week 8. A positive change from week 8 to week 9 indicates worsening.


Enrollment: 389
Study Start Date: August 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 100 mg
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
Drug: LCZ696
LCZ696
Drug: Placebo
matching placebo to LCZ696
Experimental: LCZ696 200 mg
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
Drug: LCZ696
LCZ696
Drug: Placebo
matching placebo to LCZ696
Experimental: LCZ696 400 mg
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
Drug: LCZ696
LCZ696
Drug: Placebo
matching placebo to LCZ696
Placebo Comparator: Placebo
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
Drug: Placebo
matching placebo to LCZ696

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must give written informed consent before any assessment is performed.
  2. Patients with mild to moderate essential hypertension, untreated or currently taking antihypertensive therapy (mean sitting diastolic blood pressure ≥ 95 mmHg and < 110 mmHg, and mean sitting systolic blood pressure ≥ 140 mmHg and < 180 mmHg).
  3. Patients must be willing and able to undergo ambulatory blood pressure monitoring for a 24-hr period at the beginning and the end of the 8-week treatment.
  4. Patient must be able to communicate and comply with all study requirements and demonstrate good medication compliance.

Exclusion Criteria:

  1. Patients with severe hypertension.
  2. Patients with history of angioedema, drug-related or otherwise
  3. Pregnant or nursing women
  4. Women of child-bearing potential , who do not use adequate birth control methods
  5. History or evidence of a secondary form of hypertension.
  6. History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind, stroke, TIA, carotid artery stenosis, aortic aneurysm, or peripheral arterial disease.
  7. Diabetes mellitus.
  8. Previous or current diagnosis of heart failure (NYHA Class II-IV).
  9. Clinically significant valvular heart disease at the time of screening.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01193101

Locations
China, Hebei
Novartis Investigative Site
Shijiazhuang, Hebei, China, 050000
China, Tianjin
Novartis Investigative Site
Tianjin, Tianjin, China, 300142
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310009
China
Novartis Investigative Site
Beijing, China, 100044
Novartis Investigative Site
Beijing, China, 100730
Novartis Investigative Site
Chongqing, China, 400042
Japan
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 231-0023
Novartis Investigative Site
Shimotsuke-city, Tochigi, Japan, 329-0498
Novartis Investigative Site
Bunkyo-ku, Tokyo, Japan, 113-8655
Novartis Investigative Site
Bunkyo-ku, Tokyo, Japan, 113-0031
Novartis Investigative Site
Chiyoda-ku, Tokyo, Japan, 100-0005
Novartis Investigative Site
Kiyose-city, Tokyo, Japan, 204-0021
Novartis Investigative Site
Kunitachi, Tokyo, Japan, 186-0001
Novartis Investigative Site
Minato-ku, Tokyo, Japan, 105-7390
Novartis Investigative Site
Minato-ku, Tokyo, Japan, 108-0075
Novartis Investigative Site
Ota-ku, Tokyo, Japan, 143-0023
Novartis Investigative Site
Shinagawa-ku, Tokyo, Japan, 142-0063
Novartis Investigative Site
Shinagawa-ku, Tokyo, Japan, 141-0032
Novartis Investigative Site
Shinagawa-ku, Tokyo, Japan, 142-0053
Novartis Investigative Site
Toshima-ku, Tokyo, Japan, 171-0021
Korea, Republic of
Novartis Investigative Site
Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 137-701
Novartis Investigative Site
Koyang, Kyunggi, Korea, Republic of, 410-719
Novartis Investigative Site
Daegu, Korea, Republic of, 705-703
Novartis Investigative Site
Seoul, Korea, Republic of, 150-950
Novartis Investigative Site
Seoul, Korea, Republic of, 152-703
Taiwan
Novartis Investigative Site
Changhua, Taiwan, 500
Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, 10002
Novartis Investigative Site
Taipei, Taiwan, 114
Novartis Investigative Site
Taipei, Taiwan, 10449
Thailand
Novartis Investigative Site
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 by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01193101     History of Changes
Other Study ID Numbers: CLCZ696A2219
Study First Received: August 26, 2010
Results First Received: July 23, 2015
Last Updated: July 23, 2015
Health Authority: United States: Food and Drug Administration
China: Food and Drug Administration
Korea: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Taiwan: Department of Health
Thailand: Ministry of Public Health

Keywords provided by Novartis:
hypertension
blood pressure
LCZ696
dual-acting
neprilysin
nep inhibitor
vasopeptidase
angiotensin receptor
ARNi
Essential hypertension

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 02, 2015