E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
To demonstrate the efficacy of the combinations of valsartan/amlodipine 160/10 or 160/5 mg, in patients with essential hypertension not adequately controlled on valsartan 160 mg monotherapy, by testing the hypothesis that either combination of valsartan/amlodipine 160/10 or 160/5 mg produces superior reduction in MSDBP from baseline to 8 weeks compared to valsartan 160 mg alone. |
|
E.2.2 | Secondary objectives of the trial |
1. To explore the efficacy of the combination of valsartan/amlodipine 160/10 compared to 160/5 mg, in patients with essential hypertension not adequately controlled on valsartan 160 mg monotherapy 2. To explore the efficacy of the combinations of valsartan/amlodipine 160/10 or 160/5 mg, in patients with essential hypertension not adequately controlled on valsartan 160 mg monotherapy 3. To explore the efficacy of the combination of valsartan/amlodipine 160/10 compared to 160/5 mg, in patients with essential hypertension not adequately controlled on valsartan 160 mg monotherapy 4. To explore responder rates at the end of the study; 5. To explore the safety and tolerability of these three treatments.
|
|
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. Female patients must be either post-menopausal for one year or surgically sterile, or using effective contraceptive methods such as barrier method with spermicide or an intra-uterine device. Hormonal contraceptive use is disallowed 2. Patients with essential diastolic hypertension measured by calibrated standard aneroid or mercury sphygmomanometer. At Visit 1 (week -8 to -4), patients not treated with antihypertensive medications MUST have a MSDBP of ≥ 95 mmHg and < 110 mmHg; those patients treated with antihypertensive medication MUST have a MSDBP of < 110 mmHg. At Visit 2, all patients MUST have a MSDBP of ≥ 95 mmHg and < 110 mmHg. At Visit 3, all patients MUST have a MSDBP of ≥ 90 mmHg and < 110 mmHg 3. Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent)
|
|
E.4 | Principal exclusion criteria |
1. Severe hypertension (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 180 mmHg) 2. Inability to completely discontinue all prior antihypertensive medications safely for a period of 1 to 4 weeks as required by the protocol 3. Known Keith-Wagener grade III or IV hypertensive retinopathy 4. History of hypertensive encephalopathy or cerebrovascular accident at any time prior to Visit 1 (week -8 to -4) 5. Transient ischemic attack, myocardial infarction, all types of revascularization procedures at any time prior to Visit 1 (week -8 to -4) 6. Heart failure requiring treatment 7. Second or third degree heart block without a pacemaker 8. Concomitant refractory angina pectoris 9. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia 10. Clinically significant valvular heart disease 11. Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing Disease, pheochromocytoma, polycystic kidney disease, etc… 12. Diabetic patients requiring insulin treatment 13. Type 2 diabetics with poor glucose control defined as a glycosylated hemoglobin (HbA1c) > 7% at Visit 1 14. Administration of any agent indicated for the treatment of hypertension within a minimum of 1 week prior to enrolling into the single-blind run-in phase of the study (Visit 2, week -4), with the permitted exception of those antihypertensive medications requiring tapering down commencing at Visit 1 (week -8 to -4) 15. Known or suspected contraindications, including a history of allergy to angiotensin receptor blockers or calcium channel blockers 16. 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 active inflammatory bowel syndrome within 12 months prior to Visit 1 (week -8 to -4), currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator 17. Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury within 12 months of Visit 1 (week -8 to -4) 18. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values > 2 x ULN at Visit 1 (week -8 to -4), a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt 19. Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 mg/dL for males or 1.3 mg/dL for females, a history of dialysis, or a history of nephritic syndrome 20. Sodium depletion 21. History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the past five years 22. Pregnant or breast feeding women 23. Any condition - not identified in the protocol - that in the opinion of the investigator or the Novartis monitor would jeopardize the evaluation of efficacy or safety 24. Any surgical or medical conditions which, at the discretion of the investigator, 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 25. History of drug or alcohol abuse within the last 2 years 26. History of noncompliance to medical regimens, or patients unwilling to comply with the study protocol 27. Participation in any investigational drug trial within 30 days prior to Visit 1 (week -8 to -4) 28. Prior participation in any valsartan/amlodipine protocol 29. Unwillingness or inability to give informed consent 30. Persons directly involved in the execution of this protocol
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Mean sitting systolic and diastolic blood pressure.
Others: • Vital signs including mean sitting systolic and diastolic blood pressure and heart rate • Hematology, blood chemistry and pregnancy tests • Physical examination
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |