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
Overview
- Phase
- Phase 3
- Intervention
- Valsartan 160 mg capsules
- Conditions
- Essential Hypertension
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 1183
- Locations
- 12
- Primary Endpoint
- Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Investigators
Eligibility 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
Arms & Interventions
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.
Intervention: Valsartan 160 mg capsules
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.
Intervention: Amlodipine 5 mg capsules
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.
Intervention: placebo
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.
Intervention: Valsartan 160 mg capsules
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.
Intervention: Amlodipine 5 mg capsules
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.
Intervention: placebo
Outcomes
Primary Outcomes
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
Time Frame: Baseline to Week 8
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
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 Outcomes
- Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8(Baseline to Week 8)
- Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12(Baseline to Weeks 4, 8, and 12)
- Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12(Baseline to Weeks 4, 8, and 12)