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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00699192
• Other study ID #: CVAA489A2318
• Status: Completed
• Phase: Phase 3
• First received: June 9, 2008
• Last updated: May 4, 2011
• Start date: May 2008
• Est. completion date: May 2009

Study information

• Verified date: May 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)Hungary: Országos Gyógyszerészeti IntézetItaly: Ministry of HealthSlovakia: State Institute for Drug ControlSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 965
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Amlodipine 5 mg
1 capsule amlodipine 5 mg orally once daily
• Valsartan 80 mg
1 capsule valsartan 80 mg orally once daily
• Valsartan 40 mg
1 capsule valsartan 40 mg orally once daily
• Placebo
1 capsule placebo to match valsartan orally once daily

Locations

Country	Name	City	State
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
Finland	Investigative site Finland	Helsinki
Finland	Investigative site Finland	Joensuu
Finland	Investigative site Finland	Kerava
Finland	Investigative site Finland	Tampere
France	Investigative site France	Paris
Germany	Investigative site Germany	Berlin
Hungary	Investigative site Hungary	Budapest
Italy	Investigative site Italy	Rome
Poland	Investigative site Poland	Warsaw
Slovakia	Investigative site Slovakia	Bratislava
Spain	Investigative site Spain	Valencia
Sweden	Investigative site Sweden	Malmo

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Czech Republic,  Finland,  France,  Germany,  Hungary,  Italy,  Poland,  Slovakia,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of 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. A negative change from baseline indicates lowered BP.	Baseline to end of study (Week 8)	No
Secondary	Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of 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. A negative change from baseline indicates lowered BP.	Baseline to end of study (Week 8)	No
Secondary	Percentage of Patients Achieving a Systolic Blood Pressure Response at Week 8	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.	Baseline to end of study (Week 8)	No
Secondary	Percentage of Patients Achieving Systolic Blood Pressure Control at the End of the Study (Week 8)	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.	End of study (Week 8)	No
Secondary	Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8)	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.	End of study (Week 8)	No