Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects - Full Text View

Purpose

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

Condition	Intervention	Phase
Hypertension Concurrent Obesity	Drug: LCZ696 Drug: amlodipine Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title:	A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

Resource links provided by NLM:

Drug Information available for: Amlodipine Amlodipine besylate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change From Baseline in Insulin Sensitivity Index [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

Secondary Outcome Measures:

Local Adipose Tissue Lipolysis, Glycerol Concentrations [ Time Frame: 57 days ] [ Designated as safety issue: No ]
Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.
Oxidative Metabolism [ Time Frame: 57 days ] [ Designated as safety issue: No ]
Oxidative metabolism was assessed by indirect calorimetry.
Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
Adverse event monitoring was conducted throughout the study.


Enrollment:	98
Study Start Date:	October 2012
Study Completion Date:	July 2013
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: amlodipine amlodipine was provided as 5 mg tablets. Drug: Placebo Matching placebo to LCZ696 and amlodipine.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631864

Locations


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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01631864 History of Changes
Other Study ID Numbers:	CLCZ696B2207 2012-002606-40
Study First Received:	June 27, 2012
Results First Received:	July 11, 2015
Last Updated:	July 11, 2015
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices (BfArM) Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:


Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696

Additional relevant MeSH terms:


Hypertension Vascular Diseases Cardiovascular Diseases Amlodipine LCZ 696 Antihypertensive Agents	Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Vasodilator Agents Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on September 26, 2016