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 |
• Evaluate the superior efficacy of the combination of aliskiren 300 mg and losartan 100 mg by testing the hypothesis of regression of left ventricular hypertrophy, as measured by the change in LVMI from baseline to end of study using MRI, when compared to losartan 100 mg. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the efficacy of aliskiren 300 mg compared to losartan 100 mg on the regression of left ventricular hypertrophy, as measured by the change in LVMI from baseline to end of study using MRI. • Evaluate the efficacy of the combination of aliskiren 300 mg and losartan 100 mg compared to losartan 100 mg on the change in LVH parameters from baseline to the end of study as assessed by MRI. • Evaluate the effect of aliskiren 300 mg compared to losartan 100 mg on the change in LVH parameters from baseline to the end of study, as assessed by MRI. • Evaluate the effect of the combination of aliskiren 300 mg and losartan 100 mg compared to each of the component monotherapies on the change in LVH parameters from baseline to the end of study, as assessed by centrally read ECG.
For full list of secondary objectives 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. Outpatients 18 to 80 years of age. 2. Male and female patients are eligible. Female patients must be either post-menopausal for one year, surgically sterile or using effective method of spermicide, or using an intrauterine device. 3. Patients with a history of essential hypertension. 4. Patients newly diagnosed with essential hypertension with a BP (MSDBP ≥ 90 mmHg and < 110 mmHg and MSSBP ≥ 140 mmHg and < 180 mmHg) at the Study Visit 3. 5. Patients with a BMI > 25 kg/m2. 6. Patients with LVH (LVWT ≥ 1.3 cm) confirmed by the ECHO core laboratory prior to Study Visit 3. 7. Patients who are eligible, 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 |
1. Patients treated with an ACE or an ARB within 3 months of study entry (Study Visit 1) who are unable or unwilling to undergo the 3 month washout period. 2. Patients treated with an ACE and ARB combination at study entry (Study Visit 1). 3. Known secondary hypertension of any etiology (e.g., uncorrected renal artery stenosis). 4. Hypertrophic cardiomyopathies due to etiologies other than hypertension (i.e., idiopathic or valvular). Hemodynamically significant mitral stenosis or lesions of the left ventricular outflow tract including aortic stenosis or hypertrophic obstructive cardiomyopathy. 5. Severe refractory hypertension defined as MSSBP ≥ 180 mmHg and/or MSDBP ≥ 110 mmHg) at Study Visit 1. 6. Patients currently under treatment with disallowed medications (including antihypertensive agents given for other indications e.g. beta blockers being given for ischemic heart disease) which in the opinion of the investigator cannot be discontinued prior to entry in the study. 7. Secondary forms of cardiomyopathy such as restrictive cardiomyopathy or infective cardiomyopathy (e.g., Chagas’ disease). 8. History of symptomatic heart failure (NYHA classes II-IV) or a LVEF ≤ 40% confirmed by the ECHO core laboratory prior to Study Visit 3. 9. Myocardial infarction or coronary revascularization (CABG or PCI), within 6 months of Study Visit 1. 10. Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1. 11. Serum potassium ≥ 5.2 mEq/L, or dehydration at Study Visit 1. 12. Use of pacemakers, ICD, defibrillators or any device which interferes with an MRI. 13. Patients with non-sinus rhythm or frequent extrasystoles (>6/min). 14. Patients who cannot lie supine for at least 30 minutes. 15. Patients who cannot hold their breath for 15 seconds. 16. Presence of cranial aneurysm clips, ocular metallic shards, or coronary artery metal stents. 17. Patients whose body structure (e.g., weight, height, body circumference, etc.) exceeds the restrictions of the local site MRI instrument. 18. Patients who are morbidly obese with a BMI ≥ 42 kg/m2. 19. Significant claustrophobia (not responsive to light intravenous anxiolytics). 20. Patients employed as a night shift worker. 21. Arm circumference ≥ 50 cm. 22. Current abuse or recent history of alcohol or other drug substance abuse (past 12 months). 23. Significant non-cardiovascular illness or condition likely to result in death prior to trial completion, e.g., major organ transplant (life expectancy < 1 year). 24. Patients considering undergoing elective gastric bypass surgery, or any other bariatric surgical procedures at any time after Study Visit 1. 25. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs (for list see protocol) 26. 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. 27. History of noncompliance to medical regimens or unwillingness to comply with the study protocol. 28. Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety. 29. Persons directly involved in the execution of this protocol. 30. Patients who previously entered an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. 31. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. 32. Known or suspected contraindications to or history of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (e.g., renin inhibitors and ARBs) as the study drugs. 33. 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. 34. 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). 35. 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 definition of post-menopausal.(see protocol)
For all criteria see full protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for this study is change from baseline to end of study in LVMI as measured by MRI. |
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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 | Yes |
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 | Information not present in EudraCT |
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 | 22 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 22 |