Clinical Trial Results:
A randomized, 8-week, double-blind, parallel-group, activecontrolled,
multi-center study to evaluate the efficacy and
safety of LCZ696 200 mg in comparison with olmesartan 20
mg in patients with essential hypertension not adequately
responsive to olmesartan 20 mg treatment
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
Summary
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EudraCT number |
2013-001783-36 |
Trial protocol |
ES |
Global end of trial date |
14 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 May 2016
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First version publication date |
20 May 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CLCZ696A2318
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Aug 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Aug 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of LCZ696 200 mg compared to olmesartan 20 mg in patients with
essential hypertension that do not have a satisfactory response to olmesartan 20 mg by
testing the hypothesis of superior reduction in mean 24-hour ambulatory systolic blood
pressure (maSBP) after 8 weeks of treatment
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Sep 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 62
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Country: Number of subjects enrolled |
Spain: 38
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Country: Number of subjects enrolled |
Guatemala: 21
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Country: Number of subjects enrolled |
Philippines: 40
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Country: Number of subjects enrolled |
Russian Federation: 42
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Country: Number of subjects enrolled |
United States: 172
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Worldwide total number of subjects |
375
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
287
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From 65 to 84 years |
87
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85 years and over |
1
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Randomized 376 patients but one was incorrectly randomized to the olmesartan 20 mg treatment but did not receive any double-blind medication, and hence was excluded from analysis sets. | |||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Data analyst, Assessor, Subject | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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LCZ696 200 mg | |||||||||||||||||||||||||||||||||||||||
Arm description |
Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
sacubitril/valsartan
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Investigational medicinal product code |
LCZ696
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
LCZ696 200 mg
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Arm title
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Olmesartan 20 mg | |||||||||||||||||||||||||||||||||||||||
Arm description |
Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Olmesartan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Olmesartan 20 mg
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Baseline characteristics reporting groups
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Reporting group title |
LCZ696 200 mg
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Reporting group description |
Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Olmesartan 20 mg
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Reporting group description |
Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LCZ696 200 mg
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Reporting group description |
Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks. | ||
Reporting group title |
Olmesartan 20 mg
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Reporting group description |
Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks. |
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End point title |
Change from baseline in 24-hour mean ambulatory systolic blood pressure (maSBP) | ||||||||||||
End point description |
Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.
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End point type |
Primary
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End point timeframe |
baseline, 8 weeks
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Statistical analysis title |
Change from baseline in 24-hour (maSBP) | ||||||||||||
Comparison groups |
LCZ696 200 mg v Olmesartan 20 mg
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Number of subjects included in analysis |
331
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-3.19
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-4.73 | ||||||||||||
upper limit |
-1.65 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.78
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End point title |
Change from baseline in mean 24-hour ambulatory diastolic blood pressure (maDBP) | ||||||||||||
End point description |
Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The 24-hour ABPM measurements are performed beginning 24 hours prior to baseline and week 8 visits.
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Change from baseline in mean sitting systolic blood pressure (msSBP) | ||||||||||||
End point description |
Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Change from baseline in mean sitting diastolic blood pressure (msDBP) | ||||||||||||
End point description |
Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Change from baseline in office pulse pressure | ||||||||||||
End point description |
Mean sitting pulse pressure (msPP) will be calculated at screening through end of study at every visit. Mean sitting pulse pressure is calculated as msSBP-msDBP.
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients achieving successful overall blood pressure control | |||||||||
End point description |
Successful overall blood pressure control is defined as both msSBP/msDBP <140/90 mmHg
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End point type |
Secondary
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End point timeframe |
8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients achieving successful mean sitting systolic blood pressure (msSBP) control | |||||||||
End point description |
Successful mean sitting systolic blood pressure control is defined as msSBP <140 mmHg
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End point type |
Secondary
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End point timeframe |
8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients achieving successful mean sitting diastolic blood pressure (msDBP) control | |||||||||
End point description |
Successful mean sitting diastolic blood pressure control is defined as msDBP <90 mmHg or reduction >=10 mmHg
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End point type |
Secondary
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End point timeframe |
8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients achieving successful mean sitting systolic blood pressure (msSBP) response | |||||||||
End point description |
Successful mean sitting systolic blood pressure response is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients achieving successful mean sitting diastolic blood pressure (msDBP) response | |||||||||
End point description |
Successful mean sitting diastolic blood pressure response is defined as msDBP <90 mmHg or a reduction ≥10 mmHg from baseline.
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End point type |
Secondary
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End point timeframe |
baseline, 8 weeks
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No statistical analyses for this end point |
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End point title |
Number of patients with total adverse events, serious adverse events and death | ||||||||||||||||||
End point description |
Number of patients with total adverse events, serious adverse events and death were reported.
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End point type |
Secondary
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End point timeframe |
8 weeks
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
LCZ696 200 mg
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Reporting group description |
LCZ696 200 mg | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OLMESARTAN 20 mg
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Reporting group description |
OLMESARTAN 20 mg | |||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |