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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Hypertension; Abdominal Obesity

Treatments: Drug: Aliskiren; Drug: Placebo of amlodipine; Drug: Placebo of Aliskiren; Drug: Amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00498433

CSPP100A2238

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 2 patient groups

Aliskiren

Experimental group

Description:

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.

Treatment:

Drug: Placebo of Aliskiren

Drug: Placebo of amlodipine

Drug: Aliskiren

Amlodipine

Active Comparator group

Description:

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

Treatment:

Drug: Placebo of Aliskiren

Drug: Amlodipine