Clinical trial NCT01631864: Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
Official title: A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Concurrent Obesity
Keywords: Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-06-29
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This study investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Insulin Sensitivity Index
timeFrame: baseline, 8 weeks
Secondary outcomes:
measure: Local Adipose Tissue Lipolysis, Glycerol Concentrations
timeFrame: 57 days
measure: Oxidative Metabolism
timeFrame: 57 days
measure: Number of Participants With Adverse Events, Serious Adverse Events and Deaths
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Neuss
country: Germany
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.