Efficacy and Safety of Valsartan and Amlodipine (± HCTZ) in Adults With Moderate, Inadequately Controlled Hypertension - Full Text View

Purpose

This study will evaluate the efficacy and safety of valsartan and amlodipine in fixed dose combination in adults with moderate, inadequately controlled hypertension. There was an optional study extension for eligible patients who wanted to participate that contains the triple therapy (ie, hydrochlorothiazide+ amlodipine/valsartan).

Condition	Intervention	Phase
Hypertension	Drug: Amlodipine Drug: Olmesartan medoxomil Drug: Amlodipine+valsartan Drug: Hydrochlorothiazide	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Multicenter Study to Evaluate the Efficacy and Tolerability of a 4 Week Therapy With the Fixed Dose Combination of Amlodipine 10 mg Plus Valsartan 160 mg in Hypertensive Patients Not Adequately Responding to a 4 Week Therapy With the Free Combination of an Angiotensin Receptor Blocker (Olmesartan 20 mg) Plus Amlodipine 10 mg

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Hydrochlorothiazide Amlodipine Amlodipine besylate Valsartan Olmesartan Olmesartan medoxomil

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study [ Time Frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study [ Time Frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) ] [ Designated as safety issue: No ]
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.

Secondary Outcome Measures:

Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study [ Time Frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in Sitting Pulse Pressure During the Core Phase of the Study [ Time Frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in Sitting Pulse Rate During the Core Phase of the Study [ Time Frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study [ Time Frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
Normalized Blood Pressure was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg.
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study [ Time Frame: Baseline of Phase 2 (Week 4) to end of Phase 2 (Week 8) ] [ Designated as safety issue: No ]
Blood pressure response was defined as msSBP < 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 (Week 8) compared to Baseline in Phase 2 (week 4) or a msDBP < 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2.
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study [ Time Frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) ] [ Designated as safety issue: No ]
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in Sitting Pulse Pressure During the Extension Phase of the Study [ Time Frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) ] [ Designated as safety issue: No ]
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in Sitting Pulse Rate During the Extension Phase of the Study [ Time Frame: Baseline Phase 3 (Week 8) to end of Phase 3 (week 12) ] [ Designated as safety issue: No ]
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study [ Time Frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) ] [ Designated as safety issue: No ]
Normalized Blood Pressure was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg.
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study [ Time Frame: Baseline of Phase 3 (Week 8) to end of Phase 3 (Week 12) ] [ Designated as safety issue: No ]
Blood pressure response was defined as msSBP < 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 3 compared to Baseline in Phase 3 or a msDBP < 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 3 compared to Baseline in Phase 3.

Enrollment:	257
Study Start Date:	July 2007
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Amlodipine(AML)+olmesartan, AML+valsartan, AML+valsartan+HCTZ During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the treatment Phase 2 of the study participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg.	Drug: Amlodipine Amlodipine supplied as 5 mg tablets, taken orally once a day during Treatment Phase 1 only. Drug: Olmesartan medoxomil Olmesartan medoxomil supplied as 10 mg tablets taken once a day during Treatment Phase 1 only. Drug: Amlodipine+valsartan Fixed-dose combination of amlodipine 10 mg plus valsartan 160 mg tablet taken orally once a day during Treatment Phase 2 and Extension Phase. Other Name: Exforge Drug: Hydrochlorothiazide Hydrochlorothiazide (HCTZ) 12.5 mg tablets taken once a day during the Extension Phase. Other Name: Sandoz

Arms

Assigned Interventions

Experimental: Amlodipine(AML)+olmesartan, AML+valsartan, AML+valsartan+HCTZ

During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the treatment Phase 2 of the study participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg.

Drug: Amlodipine

Amlodipine supplied as 5 mg tablets, taken orally once a day during Treatment Phase 1 only.

Drug: Olmesartan medoxomil

Olmesartan medoxomil supplied as 10 mg tablets taken once a day during Treatment Phase 1 only.

Drug: Amlodipine+valsartan

Fixed-dose combination of amlodipine 10 mg plus valsartan 160 mg tablet taken orally once a day during Treatment Phase 2 and Extension Phase.

Other Name: Exforge

Drug: Hydrochlorothiazide

Hydrochlorothiazide (HCTZ) 12.5 mg tablets taken once a day during the Extension Phase.

Other Name: Sandoz

Detailed Description:

Title of study extension: An open-label, multicenter extension to evaluate the efficacy and tolerability of a 4 week therapy with hydrochlorothiazide 12.5 mg plus amlodipine 10 mg/valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy each with the combinations of olmesartan 20 mg plus amlodipine 10 mg followed by amlodipine 10 mg/valsartan 160 mg

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for Core study:

Male or female patients (>=18 years)
Females must be either post-menopausal for one year, surgically sterile or using effective contraceptive methods
Patients with essential hypertension (diastolic blood pressure >=100 mmHg and <110 mmHg)

Inclusion Criteria for Extension:

- Patients had to have a msSBP >= 140 mmHg and/or msDBP >= 90 mmHg at week 8 ie, end of core study.

Exclusion Criteria for Core study:

Severe hypertension (diastolic blood pressure >=110 mmHg or systolic blood pressure >= 180 mmHg)
Pregnant or nursing women
Treated hypertensive patients with controlled hypertension under current therapy
A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and heart failure NYHA II - IV

Exclusion Criteria for Extension:

prematurely discontinued the core study
failed to comply with the core study protocol

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523744

Locations

Germany
Novartis Investigative Site, , Germany
Schwerin, Germany
30 sites in Germany
TBD, Germany

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis Pharmaceuticals

Sponsor GmbH

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00523744 History of Changes
Other Study ID Numbers:	CVAA489ADE06
Study First Received:	August 30, 2007
Results First Received:	January 10, 2011
Last Updated:	June 8, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:

hypertension, valsartan, amlodipine

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Valsartan
Olmesartan medoxomil
Amlodipine, valsartan drug combination
Amlodipine
Olmesartan
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents

Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Calcium Channel Blockers
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers

ClinicalTrials.gov processed this record on May 23, 2013