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

Phase 2

Completed

• Conditions: Hypertension; Concurrent Obesity
• Interventions: Drug: LCZ696; Drug: amlodipine; Drug: Placebo

• Registration Number: NCT01631864
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-06-27
• Study First Submitted QC: 2012-06-28
• Study First Posted: 2012-06-29
• Study Start: 2012-10
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2015-06
• Results First Submitted: 2015-07-11
• Results First Submitted QC: 2015-07-11
• Last Update Submitted: 2015-07-11
• Results First Posted: 2015-08-10
• Last Update Posted: 2015-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCZ696	LCZ696	LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine	Placebo	amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
LCZ696	Placebo	LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine	amlodipine	amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇳🇱 Maastricht, Netherlands