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 |
To estimate the proportion of patients reaching blood pressure (BP) control, i.e. MSSBP <140 mmHg and MSDBP <90 mmHg for non-diabetics, or MSSBP <130 and MSDBP <80 for diabetic patients, after 16 weeks of treatment with a valsartan/amlodipine 160/10mg treatment strategy or a valsartan/amlodipine 160/5mg treatment strategy in hypertensive patients not controlled with monotherapy |
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E.2.2 | Secondary objectives of the trial |
To evaluate valsartan/amlodipine 160/10mg relative to valsartan/amlodipine 160/5mg in the proportion of patients reaching BP control after 8 weeks of treatment To evaluate valsartan/amlodipine 160/10mg treatment strategy relative to valsartan/amlodipine 160/5mg treatment strategy in the proportion of patients reaching BP control after 4, 12 and 16 weeks of treatment To evaluate valsartan/amlodipine 160/10mg treatment strategy relative to valsartan/amlodipine 160/5mg treatment strategy in change from baseline MSDBP and MSSBP after 4, 8, 12 and 16 weeks of treatment To estimate the proportion of patients reaching diastolic BP control (defined as MSDBP <90 mmHg, or MSDBP <80 for diabetic patients) after 4, 8, 12 and 16 weeks of treatment with two combination treatment strategies
For detailed list see full protocol |
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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 patients ≥18 years of age 2. Non-diabetic patients must have MSSBP of ≥140 mmHg and/or MSDBP ≥90 mmHg at Visits 1 and 2. Diabetic patients must have MSSBP ≥130 mmHg and/or MSDBP ≥80 mmHg at Visits 1 and 2 3. Patients treated with monotherapy at a dose considered as adequate by the investigator for a minimum of two months prior to Visit 1 4. Written informed consent to participate in the study prior to any study procedures
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E.4 | Principal exclusion criteria |
1. Known or suspected contraindications, including history of allergy to ARBs, CCB, thiazides or to drugs with similar chemical structure 2. MSSBP ≥180 mmHg and/or MSDBP ≥110 mmHg (MSSBP ≥160 mmHg and/or MSDBP ≥100 mmHg for diabetic patients) at any time between Visit 1 and Visit 2. 3. Evidence of a secondary form of hypertension, to include coarctation of the aorta, primary hyperaldosteronism, renal artery stenosis, or pheochromocytoma 4. Known Keith-Wagener grade III or IV hypertensive retinopathy 5. History of hypertensive encephalopathy, cerebrovascular accident or myocardial infarction 6. History of transient ischemic attack 12 months prior to Visit 1 7. Percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1 8. Diabetes mellitus type 1 9. Poorly controlled type 2 diabetes mellitus, i.e. glycosylated hemoglobin (HbA1c) >8.0% 10. History of heart failure Grade II - IV according to the NYHA classification 11. Second or third degree heart block without a pacemaker 12. Concomitant unstable angina pectoris 13. Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia 14. Clinically significant valvular heart disease 15. Evidence of hepatic disease as determined by one of the following: ALT or AST values >3 x UNL at visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt 16. Evidence of renal impairment as determined by one of the followings: serum creatinine >1.5 x UNL at visit 1, a history of dialysis, or a history of nephrotic syndrome 17. Serum sodium value < 135 mmol/L at visit 1 18. Serum potassium values <3.5 mmol/L or >5.5 mmol/L at visit 1 19. Any surgical or medical condition which might alter the absorption, distribution, metabolism, or excretion of any drug 20. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks post surgical bilateral oophorectomy and/or hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, hysterectomy), hormonal contraception (implantable, patch, oral), and double –barrier methods1 (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) 21. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) 22. Any surgical or medical condition 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 23. History of malignancy of any organ system within the past five years, treated or untreated, including leukemia and lymphoma (but not basal cell skin cancer) whether or not there is evidence of local recurrence of metastases 24. Any severe, life-threatening disease within the past five years 25. History of drug or alcohol abuse within the last 2 years 26. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 27. Inability to communicate and comply with all study requirements 28. 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 primary efficacy variable is the proportion of patients who reach blood pressure control at Endpoint (Week 16), defined as BP <140/90 mmHg for non-diabetic patients or BP <130/80 mmHg for diabetic patients. |
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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 | 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 | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |