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

• ClinicalTrials.gov Identifier: NCT01631864
• Recruitment Status: Completed
• First Posted: June 29, 2012
• Results First Posted: August 10, 2015
• Last Update Posted: August 10, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: June 27, 2012
• First Posted Date: June 29, 2012
• Results First Submitted Date: July 11, 2015
• Results First Posted Date: August 10, 2015
• Last Update Posted Date: August 10, 2015
• Study Start Date: October 2012
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 11, 2015)

Change From Baseline in Insulin Sensitivity Index [ Time Frame: baseline, 8 weeks ]

The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

Original Primary Outcome Measures (submitted: June 28, 2012)

Difference in insulin sensitivity index after treatment with LCZ696 or amlodipine [ Time Frame: After 8 weeks of treatment ]

The insulin sensitivity index will be assessed by hyperinsulinemic euglycemic clamp

Current Secondary Outcome Measures (submitted: July 11, 2015)

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

Original Secondary Outcome Measures (submitted: June 28, 2012)

• Subcutaneous adipose tissue lipolysis at rest [ Time Frame: After 8 weeks of treatment ]
  Assessment will by done by microdialysis.
• Oxidative metabolism at rest [ Time Frame: After 8 weeks of treatment ]
  Assessment will be done by indirect calorimetry
• Number of patients with abnormal laboratory values, vital signs, ECGs [ Time Frame: During 8 weeks of treatment ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
• Official Title: A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
• Brief Summary: This study investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Condition

• Hypertension
• Concurrent Obesity

Intervention

• 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.

Study Arms

• 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

• Publications *: Engeli S, Stinkens R, Heise T, May M, Goossens GH, Blaak EE, Havekes B, Jax T, Albrecht D, Pal P, Tegtbur U, Haufe S, Langenickel TH, Jordan J. Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension. 2018 Jan;71(1):70-77. doi: 10.1161/HYPERTENSIONAHA.117.10224. Epub 2017 Nov 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 11, 2015): 98
• Original Estimated Enrollment (submitted: June 28, 2012): 100
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Netherlands

Administrative Information

• NCT Number: NCT01631864
• Other Study ID Numbers: CLCZ696B2207; 2012-002606-40 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: June 2015