Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00437645

Purpose

This study was designed to compare the efficacy, tolerability, and safety of the combination valsartan/amlodipine 160/5 mg versus amlodipine 10 mg in patients with essential hypertension not adequately controlled (defined as mean sitting systolic blood pressure [msSBP] ≥ 130 mmHg and ≤ 160 mmHg) on amlodipine 5 mg alone. The study evaluated both the efficacy and tolerability of the treatments by providing data that assessed blood pressure and the proportion of patients developing peripheral edema.

Condition	Intervention	Phase
Essential Hypertension	Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Double-blind, Randomized, Multicenter, Parallel Group Study to Evaluate the Efficacy, Tolerability, and Safety of Treatment With the Combination of Valsartan/Amlodipine 160/5 mg Compared to Amlodipine 10 mg in Patients With Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Alone

Resource links provided by NLM:

MedlinePlus related topics: Edema High Blood Pressure

Drug Information available for: Amlodipine Amlodipine besylate Valsartan

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Percentage of Patients With Peripheral Edema From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: Yes ]
Only occurrences of peripheral edema quantified as a reported adverse event coded as peripheral edema were included in the analysis. If a patient experienced more than one occurrence of peripheral edema between Day 1 and Week 8, it was only counted once in the analysis.

Secondary Outcome Measures:

Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12 [ Time Frame: Baseline to Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12 [ Time Frame: Baseline to Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
Systolic response was defined as msSBP < 130 mmHg or at least a 20 mmHg reduction from baseline in msSBP at Weeks 4, 8, and 12. Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated.

Enrollment:	1183
Study Start Date:	January 2007
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Valsartan/amlodipine 160/5 mg Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.	Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo capsules
Active Comparator: Amlodipine 10 mg Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.	Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo capsules

Arms

Assigned Interventions

Experimental: Valsartan/amlodipine 160/5 mg

Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo

capsules

Active Comparator: Amlodipine 10 mg

Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo

capsules

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female outpatients ≥ 55 years of age
Patients with essential hypertension measured using a validated automated oscillometric device at Visit 1
Non-treated patients must have a MSSBP ≥ 140 mmHg and ≤ 160 mmHg
Patients pre-treated on monotherapy prior to Visit 1 must have MSSBP ≤ 160 mmHg
To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥ 130 mmHg and ≤ 160 mmHg
No peripheral edema at Visit 2 (randomization)
Written informed consent to participate in this study prior to any study procedures

Exclusion Criteria:

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures
Patients taking more than 1 antihypertensive medication at Visit 1
Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of pre-treated patients that require tapering down of anti-hypertensive treatments. For patients with previous antihypertensive medication that require a gradual downward titration, the tapering down should be done according to manufacturers instructions and last dose should be taken by week -2 prior to randomization
msSBP > 180 mmHg or msDBP > 110 mmHg at any time between Visit 1 and Visit 2
Evidence of a secondary form of hypertension, including but not limited to any of the following: Coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, polycystic kidney disease, or pheochromocytoma
History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1
History of heart failure Grade II - IV according to the NYHA classification
Second or third degree heart block with or without a pacemaker
Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
Concomitant unstable angina pectoris
Clinically significant valvular heart disease
Patients with Type 1 diabetes mellitus
Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator's judgment. It is recommended that Type 2 diabetic patients are adequately controlled and, if treated with medication, be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1
Evidence of hepatic disease as determined by one of the following: AST or ALT values > 2x UNL at study entry, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
Evidence of renal impairment as determined by one of the following: serum creatinine > 1.5 x UNL at visit 1, history of dialysis, or history of nephrotic syndrome
Serum potassium values > 5.5 mmol/L at study entry
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, places the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study period
Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
Any severe, life-threatening disease within the past five years
History of drug or alcohol abuse within the last 2 years
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00437645

Locations

Argentina
sites in Argentina
Agentina, Argentina
Chile
sites in Chile
Chile, Chile
Ecuador
sites in Ecuador
Ecuador, Ecuador
Finland
sites in Finland
Finland, Finland
France
sites in France
France, France
Germany
sites in Germany
Germany, Germany
Italy
sites in Italy
Italy, Italy
Norway
sites in Norway
Norway, Norway
Spain
sites in Spain
Spain, Spain
Sweden
sites in Sweden
Sweden, Sweden
Switzerland
sites in Switzerland
Switzerland, Switzerland
Turkey
sites in Turkey
Turkey, Turkey

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Chair:

Novartis Pharmaceuticals

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schrader J, Salvetti A, Calvo C, Akpinar E, Keeling L, Weisskopf M, Brunel P. The combination of amlodipine/valsartan 5/160 mg produces less peripheral oedema than amlodipine 10 mg in hypertensive patients not adequately controlled with amlodipine 5 mg. Int J Clin Pract. 2009 Feb;63(2):217-25.

Responsible Party:	Study Director, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00437645 History of Changes
Other Study ID Numbers:	CVAA489A2404
Study First Received:	February 16, 2007
Results First Received:	August 17, 2009
Last Updated:	March 31, 2011
Health Authority:	United States: Food and Drug Administration; Finland: Finnish Medicines Agency; Argentina: Ministry of Health; Chile: Instituto de Salud Publica de Chile; Ecuador: Public Health Ministry; Germany: BfArM; Norway: Norwegian Medicines Agency; Spain: Spanish Agency of Medicines; Spain: Ministry of Health and Consumption; Sweden: Medical Products Agency; Switzerland: Swissmedic; Turkey: Ministry of Health

Keywords provided by Novartis:

Essential hypertension
blood pressure
edema

valsartan
amlodipine
combination treatment

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Valsartan
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 February 12, 2012