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Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

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ClinicalTrials.gov Identifier: NCT01631864
Recruitment Status : Completed
First Posted : June 29, 2012
Results First Posted : August 10, 2015
Last Update Posted : August 10, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Conditions Hypertension
Concurrent Obesity
Interventions Drug: LCZ696
Drug: amlodipine
Drug: Placebo
Enrollment 98
Recruitment Details  
Pre-assignment Details  
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Period Title: Overall Study
Started 50 48
Completed 48 44
Not Completed 2 4
Reason Not Completed
Withdrawal by Subject             0             1
Adverse Event             2             3
Arm/Group Title LCZ696 Amlodipine Total
Hide Arm/Group Description LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks Total of all reporting groups
Overall Number of Baseline Participants 50 48 98
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 48 participants 98 participants
51.9  (9.6) 50.5  (9.4) 51.2  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 48 participants 98 participants
Female
9
  18.0%
13
  27.1%
22
  22.4%
Male
41
  82.0%
35
  72.9%
76
  77.6%
1.Primary Outcome
Title Change From Baseline in Insulin Sensitivity Index
Hide Description The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.
Time Frame baseline, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description:
LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Number of Participants Analyzed 48 41
Mean (95% Confidence Interval)
Unit of Measure: ug/kg*min/(mmol/L*pmol/L)
0.192
(0.025 to 0.359)
0.065
(-0.0116 to 0.246)
2.Secondary Outcome
Title Local Adipose Tissue Lipolysis, Glycerol Concentrations
Hide Description Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.
Time Frame 57 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description:
LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Number of Participants Analyzed 47 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: micro mol/L
82.46
(74.53 to 91.23)
65.91
(59.22 to 73.37)
3.Secondary Outcome
Title Oxidative Metabolism
Hide Description Oxidative metabolism was assessed by indirect calorimetry.
Time Frame 57 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description:
LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Number of Participants Analyzed 46 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: carbon dioxide to oxygen ratio
0.787
(0.760 to 0.814)
0.775
(0.746 to 0.804)
4.Secondary Outcome
Title Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Hide Description Adverse event monitoring was conducted throughout the study.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAS): The SAS included all randomized participants who received at least one dose of study drug.
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description:
LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Number of Participants Analyzed 50 48
Measure Type: Number
Unit of Measure: Participants
Adverse events (serious and non-serious) 30 37
Serious adverse events 1 1
Deaths 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LCZ696 Amlodipine
Hide Arm/Group Description LCZ696 400 mg plus placebo to Amlodipine once daily for 8 weeks Amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
All-Cause Mortality
LCZ696 Amlodipine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
LCZ696 Amlodipine
Affected / at Risk (%) Affected / at Risk (%)
Total   1/50 (2.00%)   1/48 (2.08%) 
Nervous system disorders     
RUPTURED CEREBRAL ANEURYSM  1  1/50 (2.00%)  0/48 (0.00%) 
Renal and urinary disorders     
NEPHROLITHIASIS  1  0/50 (0.00%)  1/48 (2.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LCZ696 Amlodipine
Affected / at Risk (%) Affected / at Risk (%)
Total   23/50 (46.00%)   26/48 (54.17%) 
Gastrointestinal disorders     
DIARRHOEA  1  3/50 (6.00%)  1/48 (2.08%) 
General disorders     
OEDEMA PERIPHERAL  1  1/50 (2.00%)  16/48 (33.33%) 
Infections and infestations     
NASOPHARYNGITIS  1  9/50 (18.00%)  8/48 (16.67%) 
Nervous system disorders     
DIZZINESS  1  3/50 (6.00%)  1/48 (2.08%) 
HEADACHE  1  4/50 (8.00%)  6/48 (12.50%) 
Skin and subcutaneous tissue disorders     
PRURITUS  1  5/50 (10.00%)  0/48 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01631864    
Other Study ID Numbers: CLCZ696B2207
2012-002606-40 ( EudraCT Number )
First Submitted: June 27, 2012
First Posted: June 29, 2012
Results First Submitted: July 11, 2015
Results First Posted: August 10, 2015
Last Update Posted: August 10, 2015