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

Phase 2

Completed

• Conditions: Hypertension
• Interventions: Drug: LCZ696; Drug: Placebo

• Registration Number: NCT01193101
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08
• Study First Submitted: 2010-08-26
• Study First Submitted QC: 2010-08-30
• Study First Posted: 2010-09-01
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Results First Submitted: 2015-07-23
• Results First Submitted QC: 2015-07-23
• Results First Posted: 2015-08-19
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-13
• Last Update Posted: 2016-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 389

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCZ696 100 mg	LCZ696	LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
LCZ696 100 mg	Placebo	LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
LCZ696 200 mg	LCZ696	LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
LCZ696 200 mg	Placebo	LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
LCZ696 400 mg	LCZ696	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.
LCZ696 400 mg	Placebo	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.
Placebo	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Baseline, 8 weeks	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

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Baseline, 8 weeks	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 Week 8 to Week 9 in msDBP and msSBP After Single-blind Placebo Withdrawal at Week 8	8 weeks, 9 weeks	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.
Change From Baseline in 24 Hour Mean Ambulatory DBP and SBP	Baseline, 8 weeks	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.
Change From Baseline in Daytime Mean Ambulatory DBP and SBP	Baseline, 8 weeks	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	Baseline, 8 weeks	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	Baseline, 8 weeks	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	Baseline, 8 weeks	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	8 weeks	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	8 weeks	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	8 weeks	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	baseline, 8 weeks	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	baseline, 8 weeks	Trough to post-dosing hour ratio at each post-dosing hour = \[trough LSM of LCZ696 - trough LSM of placebo\]/\[post-dosing hour LSM of LCZ696 - post-dosing hour LSM of placebo\]

Trial Locations

Locations (1)

Novartis Investigative Site; 🇹🇭 Chiang Mai, Thailand