Efficacy and Safety of LCZ696 Compared to Placebo in Pati... | NCT01193101

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LCZ696 100 mg	Experimental	LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.	Drug: LCZ696 Drug: Placebo
LCZ696 200 mg	Experimental	LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.	Drug: LCZ696 Drug: Placebo
LCZ696 400 mg	Experimental	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 Drug: Placebo
Placebo	Placebo Comparator	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LCZ696	Drug	LCZ696	LCZ696 100 mg LCZ696 200 mg LCZ696 400 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
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
Change From Baseline in 24 Hour Mean Ambulatory DBP and SBP

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Shijiazhuang	Hebei	050000	China
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26280447	Derived	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.
24446062	Derived	Kario K, Sun N, Chiang FT, Supasyndh O, Baek SH, Inubushi-Molessa A, Zhang Y, Gotou H, Lefkowitz M, Zhang J. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study. Hypertension. 2014 Apr;63(4):698-705. doi: 10.1161/HYPERTENSIONAHA.113.02002. Epub 2014 Jan 20.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000-11.53± 0.88 OG001-10.98± 0.89 OG002-12.45± 0.90 OG003

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo

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.

Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo

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.

Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Number

Participants

8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.

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.

Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Number

Participants

8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.

Secondary

Number of Participants Who Achieved Successful BP Control

BP control is defined as BP < 140/90 mmHg.

Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.

Posted

Number

Participants

8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.

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]

Full Analysis Set (FAS): The FAS included all randomized participants.

Posted

Number

ratio

baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts

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]

Full Analysis Set (FAS) The FAS included all randomized participants.

Posted

Number

ratio

baseline, 8 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts

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.

Only participants from the full analysis, who had values at both week 8 and week 9, were included in the analysis. The FAS included all randomized participants.

Posted

Mean

Standard Deviation

mmHg

8 weeks, 9 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	100	16	100
EG001	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.	1	101	11	101
EG002	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.	2	96	14	96
EG003	Placebo	Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.	0	92	15	92

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected100 at risk EG0010 affected101 at risk EG0021 affected96 at risk EG0030 affected92 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected100 at risk EG0010 affected101 at risk EG0021 affected96 at risk EG003
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected100 at risk EG0011 affected101 at risk EG0020 affected96 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected100 at risk EG0010 affected101 at risk EG0021 affected96 at risk EG003
Dysarthria	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected100 at risk EG0010 affected101 at risk EG0021 affected96 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected100 at risk EG0016 affected101 at risk EG0027 affected96 at risk EG0037 affected92 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0009 affected100 at risk EG0013 affected101 at risk EG0024 affected96 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected100 at risk EG0012 affected101 at risk EG0023 affected96 at risk EG003

ID	Term
D014652	Vascular Diseases
D002318	Cardiovascular Diseases