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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01631864
First received: June 27, 2012
Last updated: July 11, 2015
Last verified: June 2015

June 27, 2012
July 11, 2015
October 2012
July 2013   (final data collection date for primary outcome measure)
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.
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
Complete list of historical versions of study NCT01631864 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 seria lsupine BP and pulse measurements, laboratory evaluations (hematology, blood chemistry, urinalysis), ECG, and adverse event monitoring
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Hypertension
  • Concurrent Obesity
  • Drug: LCZ696
    LCZ696 was provided as 400 mg tablets.
  • Drug: amlodipine
    amlodipine was provided as 5 mg tablets.
  • Drug: Placebo
    Matching placebo to LCZ696 and amlodipine.
  • Experimental: LCZ696
    LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
    Interventions:
    • Drug: LCZ696
    • Drug: Placebo
  • Active Comparator: amlodipine
    amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
    Interventions:
    • Drug: amlodipine
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
98
July 2013
July 2013   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Netherlands
 
NCT01631864
CLCZ696B2207, 2012-002606-40
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP