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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Concurrent Obesity
• Intervention / Treatment: Drug: LCZ696; Drug: Placebo; Drug: amlodipine

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Neuss, Germany, 41460
    • Novartis Investigative Site
• Netherlands
  • Maastricht, Netherlands, 5800
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696; LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Drug: LCZ696; LCZ696 was provided as 400 mg tablets.; Drug: Placebo; Matching placebo to LCZ696 and amlodipine.
Active Comparator: amlodipine; amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks	Drug: Placebo; Matching placebo to LCZ696 and amlodipine.; Drug: amlodipine; amlodipine was provided as 5 mg tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Insulin Sensitivity Index	The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.	baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Adipose Tissue Lipolysis, Glycerol Concentrations	Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.	57 days
Oxidative Metabolism	Oxidative metabolism was assessed by indirect calorimetry.	57 days
Number of Participants With Adverse Events, Serious Adverse Events and Deaths	Adverse event monitoring was conducted throughout the study.	8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 27, 2012
• First Submitted That Met QC Criteria: June 28, 2012
• First Posted (Estimate): June 29, 2012

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: July 11, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin Receptor Antagonists; Amlodipine; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696B2207; 2012-002606-40 (EudraCT Number)