Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

Tracking Information
First Submitted Date ICMJE	October 5, 2007
First Posted Date ICMJE	October 26, 2007
Results First Submitted Date	August 10, 2012
Results First Posted Date	August 10, 2015
Last Update Posted Date	August 25, 2015
Study Start Date ICMJE	September 2007
Actual Primary Completion Date	July 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 11, 2015)	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: baseline, week 8 ]; Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.
Original Primary Outcome Measures ICMJE; (submitted: October 25, 2007)	Mean sitting diastolic blood pressure lowering from baseline to week 8 of LCZ696 compared to valsartan
Change History	Complete list of historical versions of study NCT00549770 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 11, 2015)	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: baseline, week 8 ]Sitting BP measurements were performed at screening through the end of the study at every study visit.; Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP [ Time Frame: 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.; Change From Baseline in Daytime maDBP and maSBP [ Time Frame: baseline, 8 weeks ]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. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm.; Change From Baseline in Nighttime maDBP and maSBP [ Time Frame: 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.; Percentage of Participants Who Achieved a Successful Response in msDBP [ Time Frame: 8 weeks ]Successful response in msDBP is defined as msDBP <90 mmHg or a reduction ≥ 10 mmHg from baseline.; Percentage of Participants Who Achieved a Successful Response in msSBP [ Time Frame: 8 weeks ]Successful response in msSBP is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.; Percentage of Participants Who Achieved Successful Control in msDBP [ Time Frame: 8 weeks ]Successful control in msDBP is defined as msDBP <90 mmHg.; Percentage of Participants Who Achieved Successful Control in msSBP [ Time Frame: 8 weeks ]Successful control in msSBP is defined as <140 mmHg.
Original Secondary Outcome Measures ICMJE; (submitted: October 25, 2007)	MSSBP/MSDBP lowering from baseline to week 8 of LCZ696 compared to placebo
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy and Safety of LCZ696A in Patients With Essential Hypertension
Official Title ICMJE	A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension
Brief Summary	This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Hypertension
Intervention ICMJE	Drug: LCZ696; Drug: Valsartan; Drug: AHU377; Drug: Placebo
Study Arms	Experimental: LCZ696 100 mg Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: LCZ696 Drug: Placebo; Experimental: LCZ696 200 mg Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: LCZ696 Drug: Placebo; Experimental: LCZ696 400 mg Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: LCZ696 Drug: Placebo; Active Comparator: Valsartan 80 mg Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: Valsartan Drug: Placebo; Active Comparator: Valsartan 160 mg Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: Valsartan Drug: Placebo; Active Comparator: Valsartan 320 mg Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Interventions: Drug: Valsartan Drug: Placebo; Experimental: AHU377 200 mg Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily. Interventions: Drug: AHU377 Drug: Placebo; Placebo Comparator: Placebo Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. Intervention: Drug: Placebo
Publications *	Andersen MB, Simonsen U, Wehland M, Pietsch J, Grimm D. LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):14-22. doi: 10.1111/bcpt.12453. Epub 2015 Sep 4. Review.; Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010 Apr 10;375(9722):1255-66. doi: 10.1016/S0140-6736(09)61966-8. Epub 2010 Mar 16.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 16, 2008)	1334
Original Estimated Enrollment ICMJE; (submitted: October 25, 2007)	1320
Actual Study Completion Date	July 2008
Actual Primary Completion Date	July 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male or females from 18 up to and including 75 years; Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs); Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2).; Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP> 95 mmHg at baseline (Visit 3); Exclusion Criteria: Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg); History of angioedema, drug-related or otherwise, as reported by the patient; Type 1 or Type 2 diabetes mellitus (according to the ADA criteria); History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc.; History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 75 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Canada, Denmark, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Poland, Russian Federation, Slovakia, Spain, Sweden, Taiwan, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00549770
Other Study ID Numbers ICMJE	CLCZ696A2201
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Novartis ( Novartis Pharmaceuticals )
Study Sponsor ICMJE	Novartis Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account	Novartis
Verification Date	August 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP