E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate the superior efficacy of the combination of valsartan/amlodipine 160/10 mg in patients with stage II hypertension, by testing the hypothesis that the valsartan/amlodipine 160/10 mg combination regimen produces a superior reduction in MSSBP from baseline compared to amlodipine 10 mg monotherapy at week 4. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the valsartan/amlodipine treatment regimen with the amlodipine treatment regimen in change from baseline MSSBP after 2 and 8 weeks of treatment. 2. To compare the valsartan/amlodipine treatment regimen with the amlodipine treatment regimen in change from baseline MSDBP after 2, 4 and 8 weeks of treatment. 3. To compare the valsartan/amlodipine treatment regimen with the amlodipine treatment regimen in the proportion of patients reaching overall BP control (MSSBP < 140 mmHg and MSDBP < 90mmHg) after 8 weeks of treatment. 4. To evaluate the safety and tolerability of the valsartan/amlodipine and amlodipine treatment regimens.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female outpatients ≥ 18 years of age. 2. Patients with stage II hypertension defined as MSSBP ≥ 160 mmHg and MSSBP < 200 mmHg, measured using a validated automated oscillometric device at Visit 2 at the study site. 3. Treatment naïve patients should have MSSBP ≥ 160 mmHg and < 200 mmHg at Visit 2. 4. Eligible patients must sign and receive a copy of written informed consent after the purpose and nature of the investigation has been clearly explained, and comprehension noted.
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E.4 | Principal exclusion criteria |
1. Known or suspected contraindications, including history of allergy or hypersensitivity to ARBs, CCBs, thiazide diuretics or to drugs with similar chemical structures. 2. Inability to discontinue all prior antihypertensive medications safely for a maximum period of up to 21 days prior to Visit 2, as required by the protocol. 3. Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of those agents that require tapering down. 4. MSSBP ≥ 200 mmHg and/or MSDBP > 120 mmHg at any time during the study. 5. Patients with controlled hypertension (MSSBP < 140 mmHg) taking more than 3 antihypertensive medications at Visit 1. 6. Patients with uncontrolled hypertension (MSSBP ≥ 140 mmHg and < 180 mmHg) taking more than two antihypertensive medications at Visit 1. 7. Patients with uncontrolled hypertension (MSSBP ≥ 180 mmHg) taking more than one antihypertensive medication at Visit 1. 8. History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), myocardial infarction or unstable angina pectoris. 9. Malignant hypertension. 10. 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. 11. Known moderate or malignant retinopathy. Moderate is defined as retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof. Malignant is defined as signs of moderate plus swelling of the optic disk. 12. Patients with Type 1 diabetes mellitus 13. Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator’s clinical judgment. Patients currently being treated for diabetes mellitus must have satisfactory metabolic control. Type 2 diabetic patients taking oral antidiabetic medication must be on a stable dose for at least 4 weeks prior to Visit 1. 14. History of heart failure Grade II - IV according to the NYHA classification. 15. Second or third degree heart block with or without a pacemaker. 16. Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia. 17. Clinically significant valvular heart disease. 18. Active gouty arthritis. 19. History of autoimmune diseases including systemic lupus erythematosus. 20. History of multiple drug allergies. 21. Evidence of hepatic disease as determined by one of the following: SGOT (AST) or SGPT (ALT) values > 2 x UNL at Visit 1, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt. 22. Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury within 12 months of Visit 1. 23. 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. 24. Serum sodium value < 132 mmol/L at Visit 1. 25. Serum potassium values < 3.2 mmol/L at Visit 1. 26. Any surgical or medical condition which might 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 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.
For detailed list of exclusion criteria see full protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change from baseline in mean sitting systolic blood pressure (MSSBP) at Endpoint (Week 4). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |