A multicenter, double-blind, randomized, parallel-group study to evaluate the safety, tolerability, and efficacy of once daily amlodipine/valsartan 5/80mg as compared to amlodipine/valsartan 5/40mg or to amlodipine 5mg once daily in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5mg once daily

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2007-004726-24-CZ
• Date of registration: 14/03/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multicenter, double-blind, randomized, parallel-group study to evaluate the safety, tolerability, and efficacy of once daily amlodipine/valsartan 5/80mg as compared to amlodipine/valsartan 5/40mg or to amlodipine 5mg once daily in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5mg once daily
• Scientific title: A multicenter, double-blind, randomized, parallel-group study to evaluate the safety, tolerability, and efficacy of once daily amlodipine/valsartan 5/80mg as compared to amlodipine/valsartan 5/40mg or to amlodipine 5mg once daily in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5mg once daily
• Date of first enrolment: 16/05/2008
• Target sample size: 670
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004726-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: yes Cross over: Other: Other trial design description: double-dummy design If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent before any assessment is performed.
2. Male or female ages 65 years and older.
3. Diagnosed as having hypertension:
• At Visit 1/Screening, naïve patients MUST have a mean seated SBP = 155 mmHg and <180 mmHg; patients undergoing washout MUST have a mean seated SBP <180 mmHg.
• At Visit 2/Single-blind run-in entry, all patients MUST have a mean seated SBP = 155 mmHg and <180 mmHg.
• At Visit 3/Core double-blind treatment period entry, all patients MUST have a mean seated SBP =145 mmHg and <180 mmHg.
4. 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.
5. Female patients must be post-menopausal for at least one year.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients with severe hypertension (mean seated SBP =180 mmHg and/or a mean seated DBP =110 mmHg).
2. Patients who have a history of secondary hypertension (including primary aldosteronism, renovascular hypertension, pheocromocytoma, etc.).
3. Patients receiving three or more antihypertensive drugs. Dual fixed dose combination therapy will be considered as two antihypertensive drugs.
4. 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.
5. Known moderate or malignant retinopathy. Moderate 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.
6. Known or suspected contraindications, including history of allergy or hypersensitivity to ARBs, CCBs, or to drugs with similar chemical structures.
7. History of cerebrovascular accident, thrombotic stroke, or transient ischemic attack.
8. Significant history of coronary artery disease (CAD) such as any history of myocardial infarction (MI), angina pectoris, and all types of revascularization procedures.
9. History of or diagnosis of congestive heart failure Grade II-IV according to the NYHA classification.
10. Clinically significant valvular heart disease.
11. All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who, in the opinion of the investigator, are not well controlled. Patients who need oral anti-diabetic medication to adequately control their Type 2 diabetes should be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1.
12. Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
13. Second or third degree heart block with or without a pacemaker.
14. Significant hepatic disease, as demonstrated by any one of the following: AST or 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.
15. Evidence of renal impairment as determined by any one of the following: 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.
16. History of clinically significant allergies including asthma and/or multiple drug allergies.
17. Any surgical or medical condition which might 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.
18. Any condition, not identified in the protocol, that, in the opinion of the investigator or the Novartis 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 requirement of the study or completing the trial period.
19. History of malignancy of a

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Essential Hypertension

Intervention(s)

Trade Name: Diovan 40mg Capsules
Product Name: Valsartan
Product Code: VAL489
Pharmaceutical Form: Capsule*
INN or Proposed INN: Valsartan
CAS Number: 137862-53-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Diovan 80mg capsules
Product Name: Valsartan
Product Code: VAL489
Pharmaceutical Form: Capsule*
INN or Proposed INN: Valsartan
CAS Number: 137862-53-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Norvasc 5mg
Product Name: amlodipine
Pharmaceutical Form: Capsule*
INN or Proposed INN: amlodipine
CAS Number: 111470-99-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: • To evaluate the overall safety and tolerability profile of a regimen of amlodipine/valsartan 5/80 mg and amlodipine/valsartan 5/40 mg (with optional titration to amlodipine/ valsartan 5/80 mg) as compared to a regimen of amlodipine 5 mg monotherapy in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5 mg monotherapy.
• To evaluate the blood pressure lowering effects of amlodipine/valsartan 5/80 mg as compared to a regimen of amlodipine/valsartan 5/40 mg (with optional titration to amlodipine/ valsartan 5/80 mg) or to a regimen of amlodipine 5 mg monotherapy.
• To evaluate changes in orthostatic blood pressure, sitting and standing pulse, and laboratory data.

Primary end point(s): The primary objective of this trial is to evaluate the overall safety and tolerability profile of a regimen of amlodipine/valsartan 5/80 mg as compared to a regimen of amlodipine/valsartan 5/40 mg (with optional titration to amlodipine/valsartan 5/80 mg) after 8 weeks of treatment in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5 mg monotherapy. The primary endpoint is at Week 8.

Variable
The parameters for the evaluation of the overall safety and tolerability profile include: the overall reporting of adverse events, serious adverse events (SAEs) including death, discontinuation due to adverse events, and notable laboratory abnormalities.

Main Objective: The primary objective of this trial is to evaluate the overall safety and tolerability profile of a regimen of amlodipine/valsartan 5/80 mg as compared to a regimen of amlodipine/valsartan 5/40 mg (with optional titration to amlodipine/valsartan 5/80 mg) after 8 weeks of treatment in elderly patients with essential hypertension not adequately controlled after four weeks on amlodipine 5 mg monotherapy. The intent of this study is to demonstrate that the safety profiles of the two amlodipine/valsartan regimens (5/80 mg and 5/40 mg optionally titrated to 5/80 mg) are comparable in elderly patients with essential hypertension.

Secondary ID(s)

2007-004726-24-FI

CVAA489A2318