Safety, Tolerability, and Efficacy of Once Daily Amlodipine/Valsartan 5/80 as Compared to Amlodipine/Valsartan 5/40 or to Amlodipine 5 mg Monotherapy in Patients 65 Years of Age and Older With Essential Hypertension

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00699192
First received: June 9, 2008
Last updated: May 4, 2011
Last verified: May 2011
  Purpose

To characterize the safety, tolerability, and efficacy profile of amlodipine/valsartan 5/80 mg as compared to amlodipine/valsartan 5/40 mg (with optional titration to 5/80 mg) and amlodipine 5 mg monotherapy in elderly patients (≥ 65 years of age) with essential hypertension. All three regimens are expected to be well tolerated.


Condition Intervention Phase
Hypertension
Drug: Amlodipine 5 mg
Drug: Valsartan 80 mg
Drug: Valsartan 40 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Parallel-group Study to Evaluate the Safety, Tolerability, and Efficacy of Once Daily Amlodipine/Valsartan 5/80 mg as Compared to Amlodipine/Valsartan 5/40 mg or to Amlodipine 5 mg Once Daily in Elderly Patients With Essential Hypertension Not Adequately Controlled After Four Weeks on Amlodipine 5 mg Once Daily

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings. A negative change from baseline indicates lowered BP.


Secondary Outcome Measures:
  • Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings. A negative change from baseline indicates lowered BP.

  • Percentage of Patients Achieving a Systolic Blood Pressure Response at Week 8 [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    A systolic blood pressure response was defined as a msSBP < 140 mmHg or ≥ 15 mmHg reduction from baseline at the end of the study (Week 8). At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings.

  • Percentage of Patients Achieving Systolic Blood Pressure Control at the End of the Study (Week 8) [ Time Frame: End of study (Week 8) ] [ Designated as safety issue: No ]
    Systolic blood pressure control was defined as a msSBP < 140 mmHg at the end of the study (Week 8). At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings.

  • Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8) [ Time Frame: End of study (Week 8) ] [ Designated as safety issue: No ]
    Overall blood pressure control was defined as a msSBP < 140 mmHg and msDBP < 90 mmHg at the end of the study (Week 8). At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings.


Enrollment: 965
Study Start Date: May 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amlodipine/Valsartan 5/80 mg
1 capsule amlodipine 5 mg, 1 capsule valsartan 80 mg once daily
Drug: Amlodipine 5 mg
1 capsule amlodipine 5 mg orally once daily
Drug: Valsartan 80 mg
1 capsule valsartan 80 mg orally once daily
Active Comparator: Amlodipine/Valsartan 5/40 mg
1 capsule amlodipine 5 mg, 1 capsule valsartan 40 mg once daily
Drug: Amlodipine 5 mg
1 capsule amlodipine 5 mg orally once daily
Drug: Valsartan 40 mg
1 capsule valsartan 40 mg orally once daily
Active Comparator: Amlodipine 5 mg
1 capsule amlodipine 5 mg, 1 capsule placebo to match valsartan once daily
Drug: Amlodipine 5 mg
1 capsule amlodipine 5 mg orally once daily
Drug: Placebo
1 capsule placebo to match valsartan orally once daily

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Provide written informed consent before any assessment was performed.
  • Male or female at least 65 years of age.
  • Diagnosed as having hypertension:

    • At Visit 1/Screening, treatment naïve patients had to have a mean seated SBP ≥ 155 mmHg and < 180 mmHg; patients undergoing washout from their previous antihypertension medication had to have a mean seated SBP <180 mmHg.
    • At Visit 2/Single-blind run-in entry, all patients had to have a mean seated SBP ≥ 155 mmHg and < 180 mmHg.
    • At Visit 3/Core double-blind treatment period entry, all patients had to have a mean seated SBP ≥ 145 mmHg and < 180 mmHg.
  • Ability to communicate and comply with all study requirements including measuring their blood pressure at home, daily as instructed, using the home blood pressure monitor provided by the Sponsor.
  • Female patients had to be post-menopausal for at least one year.

Exclusion criteria

  • Severe hypertension (mean seated SBP ≥ 180 mmHg and/or a mean seated DBP ≥ 110 mmHg).
  • History of secondary hypertension (including primary aldosteronism, renovascular hypertension, pheochromocytoma, etc.).
  • Use of three or more antihypertensive drugs. Dual fixed dose combination therapy was considered as two antihypertensive drugs.
  • Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those antihypertensive medications requiring tapering down (e.g. beta-blocker and/or clonidine) commencing with Visit 1.
  • Known moderate or malignant retinopathy. Moderate was defined as retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof; malignant defined as signs of moderate retinopathy plus swelling of the optic disk.
  • Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs with similar chemical structures.
  • History of cerebrovascular accident, thrombotic stroke, or transient ischemic attack.
  • Significant history of coronary artery disease (CAD) such as any history of myocardial infarction (MI), angina pectoris, and all types of revascularization procedures.
  • History of or diagnosis of congestive heart failure Grade II-IV according to the New York Heart Association (NYHA) classification.
  • Clinically significant valvular heart disease.
  • All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who, in the opinion of the investigator, were not well controlled. Patients who needed oral anti-diabetic medication to adequately control their Type 2 diabetes had to be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1.
  • Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
  • Second or third degree heart block with or without a pacemaker.
  • Significant hepatic disease, as demonstrated by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt.
  • Evidence of renal impairment as determined by any one of the following: glomerular filtration rate (GFR) < 50 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula at Visit 1, a history of dialysis, or a history of nephrotic syndrome.
  • History of clinically significant allergies including asthma and/or multiple drug allergies.
  • Any surgical or medical condition with the potential to significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or inactive inflammatory bowel syndrome within 12 months prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator.
  • Any condition, not identified in the protocol, that, in the opinion of the investigator or the Novartis monitor, placed the patient at higher risk from his/her participation in the study, or was likely to prevent the patient from complying with the requirement of the study or completing the trial period.
  • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there was evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  • Any chronic inflammatory condition needing chronic anti-inflammatory therapy.
  • History of drug or alcohol abuse within the last 2 years.
  • Use of investigational drugs at the time of enrollment, or within 30 days prior to Visit 1 (Week 8).
  • Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent.
  • Persons directly involved in the execution of this protocol.
  • History of non-compliance to medical regimens, or patients unwilling to comply with the study protocol.
  • Any severe, life-threatening disease within the past five years.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00699192

Locations
Czech Republic
Novartis Investigative site
Brno, Czech Republic
Investigative site Czech Republic
Chrudim, Czech Republic
Investigative sites Czech Repbulic
Hodonin, Czech Republic
Investigative site Czech Repbulic
Jicin, Czech Republic
Sites in Czech Republic
Nachod, Czech Republic
Investigative sites Czech Republic
Praha, Czech Republic
Finland
Investigative site Finland
Helsinki, Finland
Investigative site Finland
Joensuu, Finland
Investigative site Finland
Kerava, Finland
Investigative site Finland
Tampere, Finland
France
Investigative site France
Paris, France
Germany
Investigative site Germany
Berlin, Germany
Hungary
Investigative site Hungary
Budapest, Hungary
Italy
Investigative site Italy
Rome, Italy
Poland
Investigative site Poland
Warsaw, Poland
Slovakia
Investigative site Slovakia
Bratislava, Slovakia
Spain
Investigative site Spain
Valencia, Spain
Sweden
Investigative site Sweden
Malmo, Sweden
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00699192     History of Changes
Other Study ID Numbers: CVAA489A2318
Study First Received: June 9, 2008
Results First Received: January 11, 2011
Last Updated: May 4, 2011
Health Authority: Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)
Hungary: Országos Gyógyszerészeti Intézet
Italy: Ministry of Health
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Novartis:
Blood pressure
hypertension
elderly

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Valsartan
Amlodipine, valsartan drug combination
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 16, 2014