E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with both hypertension and diabetes mellitus |
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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 to: • Demonstrate the efficacy of the combination of aliskiren 300 mg and ramipril 10 mg in patients with hypertension and diabetes mellitus by testing the hypothesis of superior reduction in MSDBP from baseline when compared to the component monotherapies. • Compare the efficacy of aliskiren 300 mg to ramipril 10 mg in patients with hypertension and diabetes mellitus by testing the hypothesis that aliskiren monotherapy is non-inferior (or superior) to ramipril 10 mg in MSDBP reduction from baseline.
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E.2.2 | Secondary objectives of the trial |
• Evaluate the efficacy of the combination of aliskiren 150 mg and ramipril 5 mg compared to the component monotherapies on MSDBP reduction from baseline to 4 weeks of treatment in patients with hypertension and diabetes mellitus. • Evaluate the efficacy of aliskiren 150 mg compared to ramipril 5 mg on MSDBP reduction from baseline to 4 weeks of treatment in patients with hypertension and diabetes mellitus. • Evaluate the safety and tolerability of aliskiren 150 mg and 300 mg, given alone and in combination with ramipril 5 mg and 10 mg, in patients with hypertension and diabetes mellitus. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Outpatients 18 years of age and older. 2. Male or female patients are eligible. Female patients must be either post-menopausal for one year, surgically sterile, or using effective contraceptive methods such as oral contraceptives or an intrauterine device. 3. Patients with a documented diagnosis of Type 1 or Type 2 diabetes mellitus. Patients currently being treated for diabetes mellitus must be on a stable dose of anti-diabetic medication for at least 4 weeks prior to Visit 1. 4. Patients with essential hypertension. Patients must have a MSDBP ≥ 90 mmHg and < 110 mmHg at the visit prior to Visit 3 (Visit 2 or optional Visit 201), and a MSDBP ≥ 95 mmHg and < 110 mmHg at randomization Visit 3 (Day 1). 5. Patients must have an absolute difference of ≤ 10 mmHg in their mean sitting diastolic blood pressure (MSDBP) during the last two visits (Visits 2 and 3 or the optional Visits 201 and 3) of the single-blind run-in period of the study.
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E.4 | Principal exclusion criteria |
1. Patients who previously entered an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. 2. Severe hypertension (grade 3 WHO classification; MSDBP ≥ 110 mmHg and/or MSSBP ≥ 180 mmHg). 3. History or evidence of a secondary form of hypertension. 4. Known Keith-Wagener grade III or IV hypertensive retinopathy. 5. History of hypertensive encephalopathy or cerebrovascular accident. 6. Current diagnosis of heart failure (NYHA Class II-IV). 7. Transient ischemic cerebral attack during the 12 months prior to Visit 1. 8. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1. 9. Serum sodium less than the lower limit of normal, serum potassium < 3.5 mEq/L or ≥ 5.2 mEq/L, or dehydration at Visit 1. 10. Current angina pectoris requiring pharmacological therapy (other than those patients on a stable dose of oral or topical nitrates). 11. Second or third degree heart block without a pacemaker. 12. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. 13. Clinically significant valvular heart disease. 14. Any surgical or medical condition or treatment 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. - Currently active or previously active inflammatory bowel disease during the 12 months prior to Visit 1. - Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal 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. - Evidence of hepatic disease as determined by any one of the following: SGOT or SGPT 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. 15. History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the past five years. 16. History or evidence of drug or alcohol abuse within the last 12 months. 17. Pregnant or nursing women. 18. 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. 19. Known or suspected contraindications to the study medications, including history of allergy to ACE-Inhibitors. 20. History of noncompliance to medical regimens or unwillingness to comply with the study protocol. 21. Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety. 22. Participation in any investigational drug trial within one month of Visit 1.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change from baseline (Visit 3) in mean sitting diastolic blood pressure. The primary analysis time-point will be the Week-8 endpoint. For each patient, the last post-baseline measurement during the double-blind period will be carried forward to Week 8 as the Week-8 endpoint measurement for the variable to be analyzed |
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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 | Yes |
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 | Yes |
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 | 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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |