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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00498433
• Other study ID #: CSPP100A2238
• Status: Terminated
• Phase: Phase 2
• First received: July 8, 2007
• Last updated: September 9, 2014
• Start date: June 2007
• Est. completion date: March 2012

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abdominal Obesity
• Hypertension
• Obesity
• Obesity, Abdominal

Intervention

Drug:
• Aliskiren
300 mg tablet once daily
• Amlodipine
5 mg capsule once daily
• Placebo of Aliskiren
Matching placebo of aliskiren 300 mg tablet
• Placebo of amlodipine
Matching placebo of amlodipine 5 mg capsule

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin-Buch
Germany	Novartis Investigative Site	Hannover

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period	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).	Day 42	No
Primary	Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period	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).	Day 98	No
Primary	Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period	Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.	Day 42	No
Primary	Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period	Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.	Day 98	No
Primary	Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period	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).	Day 42	No
Primary	Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period	Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration.	Day 42	No
Primary	Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period		Day 42	No
Primary	Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period	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).	Day 42	No
Primary	Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period	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).	Day 98	No
Primary	Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period	Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.	Day 42	No
Primary	Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period	Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.	Day 98	No
Primary	Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period	Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).	Day 42	No
Primary	Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period	Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).	Day 98	No
Primary	Part 1: Renin Activity From Plasma During Aliskiren Treatment Period	Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay.	Day 42	No
Primary	Part 1: Renin Activity From Plasma During Amlodipine Treatment Period	Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay.	Day 98	No
Primary	Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period	Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.	Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Primary	Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period	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).	Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Primary	Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period		Day 98	No
Primary	Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period		Day 98	No
Secondary	Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)		Day 14 and Day 98	No
Secondary	Part 2: Change From Baseline in Official Blood Pressure		Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Secondary	Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid		Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Secondary	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)		Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Secondary	Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies)		Placebo Baseline (Day 14), Active Treatment (Day 98)	No
Secondary	Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death		98 days	Yes