E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with essential hypertension and metabolic syndrome. |
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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 objectives of this study are: 1. To demonstrate that the combination of aliskiren / ramipril / amlodipine (300/10/10 mg) has superior efficacy compared to the combinations of ramipril / amlodipine (10/10 mg) in reducing MSSBP from baseline to the end of 12 weeks of treatment in patients with hypertension and metabolic syndrome not adequately responsive to amlodipine 10 mg. 2. To demonstrate that the combination of aliskiren / amlodipine (300/10 mg) has non-inferior efficacy compared to the combinations of ramipril / amlodipine (10/10 mg) in reducing MSSBP from baseline to the end of 12 weeks of treatment in patients with hypertension and metabolic syndrome not adequately responsive to amlodipine 10 mg.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: 1. To evaluate whether the combination of aliskiren / ramipril / amlodipine (300/10/10 mg) has superior efficacy compared to the combination of ramipril / amlodipine (10/10 mg) in reducing MSDBP from baseline to the end of 12 weeks of treatment in patients with hypertension and metabolic syndrome not adequately responsive to amlodipine 10 mg. 2. To evaluate whether the combination of aliskiren / amlodipine (300/10 mg) has superior efficacy compared to the combination of ramipril / amlodipine (10 / 10 mg) in reducing MSDBP and MSSBP from baseline to the end of 12 weeks of treatment in patients with hypertension and metabolic syndrome not adequately responsive to amlodipine 10 mg. 3. To compare changes in HbA1c at 12 weeks from baseline. 4. To evaluate the safety and tolerability profile of all treatment groups. 5. To evaluate the proportion of patients achieving a blood pressure control target of < 140/90 mmHg in each treatment arm.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Outpatients 18-70 years of age and older. 2. Male or female patients are eligible. 3. Patients with a diagnosis of hypertension: • Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a MSBBP ≥ 140 mmHg and < 180 mmHg at Visit 1. • Patients treated with antihypertensive monotherapy medications must have a MSSBP ≥ 130 mmHg and < 180 mmHg at Visit 1. • Patients taking amlodipine monotherarpy with a MSSBP ≥ 130 mmHg and < 180. For patients taking amlodipine 5mg visits 1 and 2 can be combined and for patients taking amlodipine 10mg visits 1 and 3 can be combined (vist 2 not necessary). 4. All patients must have a MSSBP ≥ 140 mmHg and < 180 mmHg at Visit 3, the end of the amlodipine run-in period. 5. Patients with a diagnosis of Metabolic Syndrome (Definition of International Diabetes Federation – IDF 2006) - Central obesity - waist circumference (cm) South Asian / Chinese / Japanese / Central+South American ≥90cm ♂, ≥ 80cm ♀ Europid / Subsaharan African / Middle East ≥94cm ♂ , ≥80cm ♀ and 1 of - Fasting plasma glucose of ≥5.6mmol/l - Triglycerides ≥ 1.7 mmol/l (or on therapy) - HDL cholesterol < 1.03 mmol/l males, < 1.29 mmol/l females (or on therapy) 6. 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).
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E.4 | Principal exclusion criteria |
Patients with any of the following at Visit 1, Visit 2, Visit 3 (unless otherwise stated) will be excluded from participation in the study. 1. Previously treated in an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. 2. 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). 3. 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 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, oral), and double-barrier methods. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 4. Patients currently on antihypertensive medication(s) that require tapering of > 7 days at Visit 1. 5. Severe hypertension (an office cuff MSDBP ≥ 115 mmHg and/or MSSBP ≥ 180 mmHg). 6. History or evidence of a secondary form of hypertension. 7. Known Keith-Wagener grade III or IV hypertensive retinopathy. 8. Previous or current diagnosis of heart failure (NYHA Class II-IV). 9. History of hypertensive encephalopathy or cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI). 10. Serum sodium < 135 mEq/ L (mmol/L) at Visit 1, if confirmed on repeat sample. 11. Serum potassium < 3.5 mEq/L (mmol/L) or ≥ 5.3 mEq/L (mmol/L) at Visit 1, if confirmed on repeat sample. 12. Type 1 diabetes mellitus. 13. Type 2 diabetes mellitus if change in oral hypoglycaemic in previous 3 months.. 14. Current angina pectoris requiring pharmacological therapy. 15. Second or third degree heart block without a pacemaker. 16. Atrial fibrillation or atrial flutter at Visit 1, or potentially life threatening or any symptomatic arrhythmia during the 12 months prior to Visit 1. 17. Clinically significant valvular heart disease. 18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following: • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. • History of active inflammatory bowel disease during the 12 months prior to Visit 1. • Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal bleeding during the 3 months prior to Visit 1. • Any history of pancreatic injury, pancreatitis, or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase during the 12 months prior to Visit 1. • Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. • Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. • Current treatment with cholestyramine or colestipol resins. 19. History of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (ARB’s, ACE-I, calcium channel blockers) as the study drugs. 20. History of angioedema due to usage of an ARB or ACE-I. 21. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 22. History or evidence of drug or alcohol abuse within the last 12 months. 23. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | No |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 80 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |