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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: June 27, 2012
Last updated: September 24, 2013
Last verified: September 2013

This study will investigate the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism of fatty acids in obese hypertensive subjects.

Condition Intervention Phase
Concurrent Obesity
Drug: LCZ696
Drug: Amlodipine
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:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Difference in insulin sensitivity index after treatment with LCZ696 or amlodipine [ Time Frame: After 8 weeks of treatment ] [ Designated as safety issue: No ]
    The insulin sensitivity index will be assessed by hyperinsulinemic euglycemic clamp

Secondary Outcome Measures:
  • Subcutaneous adipose tissue lipolysis at rest [ Time Frame: After 8 weeks of treatment ] [ Designated as safety issue: No ]
    Assessment will by done by microdialysis.

  • Oxidative metabolism at rest [ Time Frame: After 8 weeks of treatment ] [ Designated as safety issue: No ]
    Assessment will be done by indirect calorimetry

  • Number of patients with abnormal laboratory values, vital signs, ECGs [ Time Frame: During 8 weeks of treatment ] [ Designated as safety issue: No ]
    Tolerability will be assessed by Physical examination, vital signs, including serial lupine BP and pulse measurements, laboratory evaluations (hematology, blood chemistry, urinalysis), ECG, and adverse event monitoring

Enrollment: 97
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 plus placebo to Amlodipine once daily for 8 weeks
Drug: LCZ696
Active Comparator: Amlodipine
Amlodipine plus placebo to LCZ696 once daily for 8 weeks
Drug: Amlodipine


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  • Women of child-bearing potential
  • Pregnant or nursing (lactating) women
  • 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01631864

Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Neuss, Germany, 41460
Novartis Investigative Site
Maastricht, Netherlands, 5800
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01631864     History of Changes
Other Study ID Numbers: CLCZ696B2207, 2012-002606-40
Study First Received: June 27, 2012
Last Updated: September 24, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices (BfArM)
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:
Hypertension, obesity, glucose metabolism lipid metabolism, LCZ696, insulin sensitivity, lipolysis

Additional relevant MeSH terms:
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on August 02, 2015