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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01631864
Recruitment Status : Completed
First Posted : June 29, 2012
Results First Posted : August 10, 2015
Last Update Posted : August 10, 2015
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

June 27, 2012
June 29, 2012
July 11, 2015
August 10, 2015
August 10, 2015
October 2012
July 2013   (Final data collection date for primary outcome measure)
Change From Baseline in Insulin Sensitivity Index [ Time Frame: baseline, 8 weeks ]
The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.
Difference in insulin sensitivity index after treatment with LCZ696 or amlodipine [ Time Frame: After 8 weeks of treatment ]
The insulin sensitivity index will be assessed by hyperinsulinemic euglycemic clamp
Complete list of historical versions of study NCT01631864 on Archive Site
  • Local Adipose Tissue Lipolysis, Glycerol Concentrations [ Time Frame: 57 days ]
    Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.
  • Oxidative Metabolism [ Time Frame: 57 days ]
    Oxidative metabolism was assessed by indirect calorimetry.
  • Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 8 weeks ]
    Adverse event monitoring was conducted throughout the study.
  • Subcutaneous adipose tissue lipolysis at rest [ Time Frame: After 8 weeks of treatment ]
    Assessment will by done by microdialysis.
  • Oxidative metabolism at rest [ Time Frame: After 8 weeks of treatment ]
    Assessment will be done by indirect calorimetry
  • Number of patients with abnormal laboratory values, vital signs, ECGs [ Time Frame: During 8 weeks of treatment ]
    Tolerability will be assessed by Physical examination, vital signs, including seria lsupine BP and pulse measurements, laboratory evaluations (hematology, blood chemistry, urinalysis), ECG, and adverse event monitoring
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Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
This study investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.
Not Provided
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Hypertension
  • Concurrent Obesity
  • Drug: LCZ696
    LCZ696 was provided as 400 mg tablets.
  • Drug: amlodipine
    amlodipine was provided as 5 mg tablets.
  • Drug: Placebo
    Matching placebo to LCZ696 and amlodipine.
  • Experimental: LCZ696
    LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
    • Drug: LCZ696
    • Drug: Placebo
  • Active Comparator: amlodipine
    amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
    • Drug: amlodipine
    • Drug: Placebo
Engeli S, Stinkens R, Heise T, May M, Goossens GH, Blaak EE, Havekes B, Jax T, Albrecht D, Pal P, Tegtbur U, Haufe S, Langenickel TH, Jordan J. Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension. 2018 Jan;71(1):70-77. doi: 10.1161/HYPERTENSIONAHA.117.10224. Epub 2017 Nov 27.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
July 2013
July 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Written informed consent must be obtained before any study assessment is performed.
  • Males and females of non-childbearing potential ≥ 18 years of age.
  • Subjects with mild to moderate essential hypertension,

    • Untreated subjects must have a mean seated SBP (msSBP) ≥ 130 mmHg and < 180 mmHg at screening.
    • Pre-treated subjects must have a msSBP ≤ 160 mmHg at screening and < 180 mmHg at the end of the washout period.
  • Waist circumference ≥ 102 cm (men) and ≥ 88 cm (women);

Exclusion criteria:

  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
  • History of angioedema, drug-related or otherwise
  • History of hypersensitivity to LCZ696, amlodipine, or drugs of similar chemical classes.
  • Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
  • Type 1 or Type 2 diabetes mellitus.
  • Dyslipidemia requiring pharmacological therapy with a fibrate or nicotinic acid.
  • Concomitant use of anti-hypertensives, anti-diabetics, or drugs with effects on glucose or lipid metabolism for the duration of the study.

Other protocol defined inclusion/exclusion criteria may apply

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Germany,   Netherlands
2012-002606-40 ( EudraCT Number )
Not Provided
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP