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

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

Official Title
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A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

Conditions
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Hypertension, Concurrent Obesity

Intervention / Treatment
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* Drug: LCZ696
* Drug: amlodipine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696