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Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension

This study has been terminated.
(Early termination resulted from interim analysis of the ALTITUDE trial)
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00498433
First received: July 8, 2007
Last updated: September 9, 2014
Last verified: September 2014

July 8, 2007
September 9, 2014
June 2007
March 2012   (final data collection date for primary outcome measure)
  • Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentrations on the last day of the aliskiren treatment periods (Day 42).
  • Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentration on the last day of the amlodipine treatment periods (Day 98).
  • Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
  • Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
  • Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine aliskiren concentration. Tissue biopsy samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).
  • Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration.
  • Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).
  • Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the amlodipine treatment periods (Day 98).
  • Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
  • Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
  • Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).
  • Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).
  • Part 1: Renin Activity From Plasma During Aliskiren Treatment Period [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay.
  • Part 1: Renin Activity From Plasma During Amlodipine Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay.
  • Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.
  • Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
    Plasma Ang II was measured prior to and 1 hour after the Insulin modified-frequently sampled intravenous glucose tolerance test (IM-FSIGT) during placebo treatment (Days 14) and active treatment(Day 98).
  • Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
  • Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
Part 1 • Concentration of aliskiren, amlodipine and RAS biomarkers in body fluids and cells in obese patients with hypertension.
Complete list of historical versions of study NCT00498433 on ClinicalTrials.gov Archive Site
  • Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle) [ Time Frame: Day 14 and Day 98 ] [ Designated as safety issue: No ]
  • Part 2: Change From Baseline in Official Blood Pressure [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
  • Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
  • Part 2: Change From Baseline in Peripheral Insulin Sensitivity in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle) [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
  • Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies) [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ] [ Designated as safety issue: No ]
  • Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death [ Time Frame: 98 days ] [ Designated as safety issue: Yes ]
• Effects of aliskiren and amlodipine on angiotensin II • Effects of aliskiren and amlodipine on biomarkers
Not Provided
Not Provided
 
Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension
Part 1: An Open Label Pilot Study to Determine Interstitial and Tissue Concentrations of Aliskiren and Effects on the Renin- Angiotensin System (RAS) in Fat and Skeletal Muscle of Hypertensive Patients With Abdominal Obesity. Part 2: A Randomized, Double Blind, 12-weeks Parallel Group Study to Compare Effects of Aliskiren 300 mg and Amlodipine 5 mg on the RAS and Lipid/Carbohydrate Metabolism in Fat and Skeletal Muscle of Hypertensive Patients With Abdominal Obesity

Part 1 determined: aliskiren, amlodipine and angiotensin II concentrations in interstitial fluid of fat and skeletal muscle; aliskiren and angiotensin II concentrations, and renin activity and concentration in fat and skeletal muscle tissues (biopsies); aliskiren, amlodipine and angiotensin II concentrations, and renin activity and concentration in plasma.

Part 2 investigated the potential for aliskiren to modulate renin-angiotensin-aldosterone system (RAAS) activity, and lipid/carbohydrate metabolism in adipose and skeletal muscle tissue in obese patients with hypertension in comparison to amlodipine.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Hypertension
  • Abdominal Obesity
  • Drug: Aliskiren
    300 mg tablet once daily
    Other Name: SPP100
  • Drug: Amlodipine
    5 mg capsule once daily
  • Drug: Placebo of Aliskiren
    Matching placebo of aliskiren 300 mg tablet
  • Drug: Placebo of amlodipine
    Matching placebo of amlodipine 5 mg capsule
  • Experimental: Aliskiren

    Part 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase (period 1) consisting of treatment with one tablet of placebo to aliskiren once daily (o.d.). This was followed by a 4 week treatment phase (period 2) consisting of treatment with 300 mg aliskiren o.d..

    Part 2: Eligible randomized patients in this arm received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks.

    Interventions:
    • Drug: Aliskiren
    • Drug: Placebo of Aliskiren
    • Drug: Placebo of amlodipine
  • Active Comparator: Amlodipine

    Part 1: After aliskiren treatment (period 2), each patient was entered into a second washout period (4 weeks) during which blood pressure was required to be ≤ 140/90 mmHg. If blood pressure exceeded 140/90 mmHg on two consecutive days (home monitoring) and was confirmed at the study center, the patient was entered into the amlodipine treatment period (period 3). In period 3, all patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.

    Part 2: Eligible patients randomized to part 2 received amlodipine 5 mg o.d. and aliskiren placebo for 12 weeks

    Interventions:
    • Drug: Amlodipine
    • Drug: Placebo of Aliskiren
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
46
March 2012
March 2012   (final data collection date for primary outcome measure)

Inclusion criteria:

PART 1:

  • Male and female patients 20 to 65 years of age with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women)
  • For patients with a history of treated hypertension, mean sitting systolic blood pressure (msSBP)/ mean sitting diastolic blood pressure (msDBP) had to be ≥ 120/80 mmHg and ≤ 160/100 mm Hg. For patients with newly diagnosed, untreated hypertension msSBP/msDBP had to be ≥ 135/85 mmHg and ≤ 160/100 mm Hg
  • Pulse rate 40 - 90 bpm

PART 2:

  • Male and female patients 18 to 65 years of age , with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women)
  • Systolic and diastolic blood pressure and pulse rate were assessed after the patient had rested for at least five (5) minutes. Vital signs had to be within the following ranges:

    1. Patients with history of treated hypertension: msSBP/msDBP ≥ 135/85 mmHg and < 160/100 mmHg at baseline
    2. Patients with newly diagnosed, untreated hypertension: msSBP/msDBP ≥ 135/85 mmHg and < 160/100 mmHg at screening and baseline.

Exclusion criteria:

PART 1

  • Hypertension Grade 2 (msSBP ≥ 160 mmHg) or Grade 3 (msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg) WHO classification
  • Current treatment with three or more antihypertensive drugs.

PART 2

  • Hypertension Grade 2 (msSBP ≥ 160 and/or msDBP ≥ 100 mmHg).
  • Current treatment with three or more antihypertensive drugs.

Other protocol-defined inclusion/exclusion criteria applied

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00498433
CSPP100A2238
Yes
Novartis
Novartis
Not Provided
Principal Investigator: Novartis Investigative site
Novartis
September 2014

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