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 |
Confirm the efficacy of aliskiren 75 mg, 150 mg and 300 mg in elderly patients with essential hypertension when given with a light meal by testing the hypothesis of superior reduction in mean sitting systolic blood pressure (msSBP) from baseline to end of study when compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the efficacy of aliskiren 75 mg, 150 mg and 300 mg in patients with essential hypertension by testing the hypothesis of superior reduction in mean sitting diastolic blood pressure (msDBP) from baseline to study end when compared to placebo. • Evaluate the effect of aliskiren 75 mg, 150 mg, 300 mg and placebo on the change from baseline in mean 24 hour ambulatory systolic blood pressure and ambulatory diastolic blood pressure in a subset of patients • Evaluate the effect of aliskiren 75 mg, 150 mg, 300 mg and placebo on the smoothness index, trough to peak ratio and morning surge of ambulatory systolic blood pressure and ambulatory diastolic blood pressure in a subset of patients • Evaluate the proportion of patients achieving blood pressure response rate as defined by msSBP < 140 mmHg and/or a ≥ 20 mmHg decrease in msSBP from baseline to end of study. • Evaluate the safety and tolerability of aliskiren 75 mg, 150 mg and 300 mg. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female outpatients 65 years of age and older. 2. 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). 3. At the randomization Visit patients must have an office msSBP greater than or equal to 150 mmHg and < 180 mmHg (msDBP <110 mmHg) with a less than or equal to 15 mmHg difference during the last two visits of the single blind run-in period |
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E.4 | Principal exclusion criteria |
1. Severe hypertension [Office msDBP ≥110 mmHg and/or mean sitting systolic blood pressure (msSBP) ≥ 180 mmHg]. 2. History or evidence of a secondary form of hypertension. 3. Known Keith-Wagener grade III or IV hypertensive retinopathy. 4. History of hypertensive encephalopathy or cerebrovascular accident, including a history of transient ischemic cerebral attack (TIA). 5. Current diagnosis of heart failure (NYHA Class II-IV). 6. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI). 7. Current angina pectoris requiring pharmacological therapy other than nitrates. 8. Second or third degree heart block without a pacemaker. 9. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. 10. Clinically significant valvular heart disease at the discretion of the principal investigator’s clinical judgment. 11. History of Type 1 diabetes, or Type 2 diabetes and glycosylated hemoglobin (HbA1c) > 8% at Visit 1. 12. Serum potassium ≥ 5.5 mEq/L at Visit 1. 13. Estimated glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 using the MDRD formula at Visit 1. 14. Known or suspected contraindications to the study medications, including history of allergy to ACE-Inhibitors or ARBs. 15. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs. 16. History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the past five years. 17. Previous participation in an investigational clinical trial within 1 month of Visit 1 18. Previous exposure to aliskiren within 3 months of Visit 1 19. 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). 20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: • women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner • women whose partners have been sterilized by vasectomy or other means • using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs), Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable Reliable contraception should be maintained throughout the study and for 14 days after study drug discontinuation. Woman are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. Additional exclusion criteria for patients in ambulatory blood pressure measurement substudy: 21. Upper arm circumference > 42 cm. 22. Third shift or night workers. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the change from baseline in trough mean sitting systolic blood pressure (msSBP) and the primary analysis time-point will be Week 8 Endpoint. |
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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 | 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 | No |
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) | 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 | 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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |