E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
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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 |
To confirm that the combination of valsartan/amlodipine 160/5mg is non-inferior to amlodipine 10mg alone when comparing the reduction of MSSBP from baseline to week 8 (Visit 4) between the two treatment groups.
To confirm that the combination of valsartan/amlodipine 160/5mg induces less peripheral edema compared to amlodipine 10mg alone up to Visit 4 (week 8) quantified as adverse event (AE) reported peripheral edema.
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E.2.2 | Secondary objectives of the trial |
• To demonstrate that the efficacy of the combination of valsartan/amlodipine 160/5mg is non-inferior in reduction of MSDBP from baseline to week 8 compared to amlodipine 10 mg alone • To compare the change from baseline in MSSBP and MSDBP after 4 and 12 weeks of treatment between the two treatment groups • To compare the systolic blood pressure responder rate (defined as MSSBP < 130 mmHg or ≥ 20 mmHg reduction from baseline) in MSSBP at week 4, 8, and 12 between the two treatment groups • To compare the proportion of patients who reach systolic blood pressure control (defined as MSSBP < 130mmHg) at week 4, 8, and 12 between the two treatment groups • To compare the proportion of patients who reach overall blood pressure control (defined as BP <140/90 mmHg for non-diabetic patients and < 130/80 mmHg for diabetic patients) at week 4, 8, and 12 between the two treatment groups • To evaluate the safety and tolerability of the two treatments
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female outpatients ≥ 55 years of age 2. 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 3. To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥130 mmHg and ≤ 160 mmHg 4. No peripheral edema at Visit 2 (randomization) 5. Written informed consent to participate in this study prior to any study procedures
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E.4 | Principal exclusion criteria |
1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant 2. Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures 3. Patients taking more than 1 antihypertensive medication at Visit 1 4. 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 5. MSSBP > 180mmHg or MSDBP 110 mmHg at any time between Visit 1 and Visit 2 6. 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 7. 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 8. History of heart failure Grade II - IV according to the NYHA classification 9. Second or third degree heart block with or without a pacemaker 10. Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia 11. Concomitant unstable angina pectoris 12. Clinically significant valvular heart disease 13. Patients with Type 1 diabetes mellitus 14. 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. 15. Evidence of hepatic disease as determined by one of the following: AST or ALT values > 2 x UNL at Visit 1, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt 16. 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 17. Serum potassium values > 5.5 mmol/L at Visit 1 18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug 19. Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period 20. Volume depletion based on the investigator’s clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values 21. Any severe, life-threatening disease within the past five years 22. History of drug or alcohol abuse within the last 2 years 23. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 24. Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent 25. Persons directly involved in the execution of this protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
The variable for the first rank-order hypothesis is the reduction of MSSBP from baseline week 8 (Visit 4) between the two treatment groups. Baseline is defined as the MSSBP at Visit 2.
The variable for the second rank-order hypothesis is the proportion of peripheral edema that occurred between Day 1 and up to and including Week 8 (Visit 4), quantified as AE reported peripheral edema. If a patient experiences more than one peripheral edema during Visit 2 and Visit 4, it will only be counted once in the analysis. |
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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 | Information not present in EudraCT |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
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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
| No |
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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |