E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015488 |
E.1.2 | Term | Essential hypertension |
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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 demonstrate that aliskiren 300 mg monotherapy exerts a greater blunting effect than valsartan 320 mg by assessing the rise in SBP at peak exercise (85% of the maximal predicted heart rate) and comparing the study baseline SBP to the end of the 48 hr dosing interval (after one missed dose), in mild to moderate hypertensive patients. |
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E.2.2 | Secondary objectives of the trial |
• To show that aliskiren 300 mg monotherapy exerts a greater blunting effect than valsartan 320 mg by assessing the rise in SBP at peak exercise (85% of the maximal predicted HR) and comparing the end of active treatment SBP to the end of the 48 hr dosing interval (after one missed dose), in mild to moderate hypertensive patients. • To evaluate the effect of aliskiren 300 mg monotherapy compared to valsartan 320 mg monotherapy on the rise of SBP during the treadmill exercise test assessed at each of the stages of the Bruce Protocol* comparing: 1) study baseline to the end of active treatment; 2) study baseline and the end of active treatment to the 48 hr dosing interval (after one missed dose). • To evaluate the overall safety and tolerability of aliskiren 300 mg compared to valsartan 320 mg monotherapies in patients during the treatment period, before and after exercise testing. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Physically active outpatients, 50 years of age or older. 2. Patients with msSBP ≥ 140 mmHg and < 180 mmHg measured at rest at Visit 2. 3. 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, barrier method with spermicidal or an intrauterine device. 4. 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). 5. Patients being able to exercise and to reach 85% of their predicted heart rate during an exercise test on a treadmill according to the Bruce Protocol at Visit 2 . |
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E.4 | Principal exclusion criteria |
For full list, please refer to the protocol.
1. Patients not confident in exercising or not able to exercise. 2. Absolute contraindication to exercise testing (see Appendix 1) 3. Hypertensive patients with msSBP ≥ 180 mmHg and/or msDBP ≥ 110 mmHg, at rest. 4. History or evidence of secondary hypertension of any etiology (e.g., uncorrected renal artery stenosis, pheochromocytoma). 5. Current diagnosis of heart failure (NYHA Class II-IV). 6. Current angina pectoris requiring pharmacological therapy (other than stable doses of oral or topical nitrates). 7. Second or third degree heart block with or without a pacemaker. 8. Concurrent potentially life-threatening arrhythmia or symptomatic arrhythmia, atrial fibrillation or atrial flutter, during the 12 months prior to Visit 1. 9. Clinically significant valvular heart disease. 10. Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at screening or baseline. 11. History of unilateral carotid artery stenosis more or equal to 70% or any endoarterectomy intervention within 6 months prior to screening visit. 12. History of hypertensive encephalopathy or cerebrovascular accident, transient ischemic cerebral attack, coronary bypass surgery, myocardial infarction or any percutaneous coronary intervention (PCI). 13. Known Keith-Wagener grade III or IV hypertensive retinopathy. 14. Patients on combination antihypertensive therapy that includes more than 2 classes of antihypertensive medications. Patients on combined antihypertensive medication that contain two classes of antihypertensive medications are considered to take two antihypertensive medications. 15. Patients taking antihypertensive medications requiring more than 28 days of tapering. 16. History of angioedema due to ACE-Is and ARBs administration. 17. History of Type 1 diabetes mellitus. 18. History of Type 2 diabetes mellitus unless patient is on stable antidiabetic medication regimen for at least 4 weeks prior to Visit 1. 19. Serum sodium less than the lower limit of normal, serum potassium < 3.5 mEq/L (corresponding to 3.5 mmol/L) or ≥ 5.3 mEq/L (corresponding to 5.3 mmol/L), or dehydration at Visit 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable will be change from baseline (Day 1) of SBP at peak vs rest (SBP at peak minus SBP at rest) during the treadmill test after a missed dose. |
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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 | Information not present in EudraCT |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |