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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01193101
• Other study ID #: CLCZ696A2219
• Status: Completed
• Phase: Phase 2
• First received: August 26, 2010
• Last updated: January 13, 2016
• Start date: August 2010
• Est. completion date: April 2011

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationChina: Food and Drug AdministrationKorea: Food and Drug AdministrationJapan: Pharmaceuticals and Medical Devices AgencyTaiwan: Department of HealthThailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 389
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• LCZ696
LCZ696
• Placebo
matching placebo to LCZ696

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Tianjin	Tianjin
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Kiyose-city	Tokyo
Japan	Novartis Investigative Site	Kunitachi	Tokyo
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Shimotsuke-city	Tochigi
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Toshima-ku	Tokyo
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Bucheon	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Koyang	Kyunggi
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Japan,  Korea, Republic of,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	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 Mean Sitting Systolic Blood Pressure (msSBP)	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 24 Hour Mean Ambulatory DBP and SBP	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. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Daytime Mean Ambulatory DBP and SBP	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.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Nighttime Mean Ambulatory DBP and SBP	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.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Mean Sitting Pulse Pressure	Mean sitting pulse pressure is the difference in msSBP and msDBP (msSBP - msDBP). A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Mean Ambulatory Pulse Pressure	Mean ambulatory pulse pressure is the difference in maSBP and maDBP (maSBP - maDBP). A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Number of Participants Who Achieved a Successful Response in msDBP	Successful response in msDBP is defined as msDBP <90 mmHg or a reduction = 10 mmHg from baseline.	8 weeks	No
Secondary	Number of Participants Who Achieved a Successful Response in msSBP	Successful response in msSBP is defined as msSBP <140 mmHg or a reduction = 20 mmHg from baseline.	8 weeks	No
Secondary	Number of Participants Who Achieved Successful BP Control	BP control is defined as BP < 140/90 mmHg.	8 weeks	No
Secondary	Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP	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]	baseline, 8 weeks	No
Secondary	Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP	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]	baseline, 8 weeks	No
Secondary	Change From Week 8 to Week 9 in msDBP and msSBP After Single-blind Placebo Withdrawal at Week 8	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.	8 weeks, 9 weeks	No