Efficacy and Safety of Valsartan and Amlodipine in Patients With Essential Hypertension

Novartis

Status and phase: Completed; Phase 3; Phase 2

Conditions: Essential Hypertension

Treatments: Drug: Valsartan + amlodipine 40/5 mg; Drug: Valsartan + amlodipine 80/5 mg; Drug: Valsartan + amlodipine 40/2.5 mg; Drug: Amlodipine 5 mg; Drug: Placebo; Drug: Valsartan 80 mg; Drug: Valsartan + amlodipine 80/2.5 mg; Drug: Valsartan 40 mg; Drug: Amlodipine 2.5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00425373

CVAA489A1301

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and efficacy of fixed combination of valsartan (40 mg and 80 mg) and amlodipine (2.5 mg and 5 mg), valsartan and amlodipine alone, and placebo in reducing blood pressure. The study will investigate the dose response relationship for the combinations, monotherapies, and placebo.

Enrollment: 1,474 patients

Sex: All

Ages: 20 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Patients with essential hypertension measured by electronic hemodynamometer. - - Patients must satisfy the following criteria.

  1. MSDBP <110 mmHg and MSSBP <180 mmHg at Visit 1
  2. MSDBP ≥ 90 mmHg and < 110 mmHg and MSSBP < 180 mmHg at Visit 2
  3. MSDBP ≥ 95 mmHg and < 110 mmHg and MSSBP < 180 mmHg at Visit 3
  4. The absolute difference in MSDBP between Visit 2 and 3 is ≤ 10 mmHg

• Male or female outpatients.

• Aged => 20 and =< 80 years (at the time of signing informed consent).

• Patients who have written informed consent to participate in this study.

Exclusion criteria

• Pregnant women, nursing (lactating) mothers, women suspected of being pregnant, or women who wish to be pregnant during the study, women of child-bearing potential.
• Patients with secondary hypertension or suspected of having secondary hypertension.
• Patients with a history of malignant hypertension.
• Patients with an inability to completely discontinue all prior antihypertensive medications safely for a period of 12 weeks as required by the protocol.
• Patients with or with a history of any of the following diseases or signs: Cardiac disease, renal disease, cerebrovascular disorder
• Patients with a clinically significant allergy (asthma on pharmacotherapy, multi-drug allergy, or drug-induced or food-induced anaphylactic reactions).
• Patients hypersensitive to AII receptor antagonists, calcium channel blockers or dihydropyridine derivatives.
• Known moderate or malignant retinopathy.
• Patients with or with a history of pancreatitis. Patients with pancreatic injury, or evidence of impaired pancreatic function/injury within 12 months of Visit 1.
• Patients with any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
• Patients with volume depletion based on the investigator's or subinvestigator's clinical judgment using vital signs, skin turgor, moistness of mucous membrane and laboratory values.
• Patients who are found to have low Na and K (Na <130 mEq/L, K <3.3mEq/L) or high in these parameters (Na ≥ 152 mEq/L, K ≥ 5.2 mEq/L) by laboratory tests at Visit 1.
• Patients with type I diabetes mellitus on treatment with insulin, or patients with type II diabetes with poor glucose control defined as a glycosylated hemoglobin (HbA1c) > 8.0% at Visit 1.
• Patients with or with a history of malignant tumors including leukemia and lymphoma, treated or untreated, within the past 5 years of Visit 1 whether or not there is evidence of local recurrence or metastases (except for localized basal cell carcinoma of the skin).
• Patients with any severe, life-threatening disease within the past 5 years. Patients with a history of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.
• Any surgical or medical condition, which in the opinion of the investigator or subinvestigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirement of the study or completing the trial period.
• Patients who have with or with a history of drug or alcohol abuse within the last 2 years of Visit 1. Patients who have received other investigational product within 12 weeks of Visit 1.
• Any chronic inflammatory condition needing chronic anti-inflammatory drug therapy.
• Persons directly involved in the execution of this study.
• Patients who are considered unlikely to comply with the requirements specified in the protocol by the investigator or subinvestigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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1,474 participants in 9 patient groups, including a placebo group

Valsartan + amlodipine 40/2.5 mg

Experimental group

Treatment:

Drug: Valsartan + amlodipine 40/2.5 mg

Valsartan + amlodipine 40/5 mg

Experimental group

Treatment:

Drug: Valsartan + amlodipine 40/5 mg

Valsartan + amlodipine 80/2.5 mg

Experimental group

Treatment:

Drug: Valsartan + amlodipine 80/2.5 mg

Valsartan + amlodipine 80/5 mg

Experimental group

Treatment:

Drug: Valsartan + amlodipine 80/5 mg

Valsartan 40 mg

Active Comparator group

Treatment:

Drug: Valsartan 40 mg

Valsartan 80 mg

Active Comparator group

Treatment:

Drug: Valsartan 80 mg

Amlodipine 2.5 mg

Active Comparator group

Treatment:

Drug: Amlodipine 2.5 mg

Amlodipine 5 mg

Active Comparator group

Treatment:

Drug: Amlodipine 5 mg

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo