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 compare the BP lowering effect of the combination of aliskiren/amlodipine 300/10 mg versus amlodipine 10 mg monotherapy in patients with moderate to severe hypertension by testing the hypothesis that the combination of aliskiren/amlodipine produces a superior reduction from baseline in mean sitting systolic blood pressure (msSBP) after 8 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives are listed below. For full list, please refer to the protocol.
• To evaluate the proportion of patients achieving blood pressure control (msSBP mmHg and msDBP < 90 mmHg), in both study arms, after 8 weeks of treatment. • To evaluate whether the combinations of aliskiren/amlodipine attenuate amlodipine-induced edema • To evaluate the overall safety and tolerability of aliskiren/amlodipine 300/10 mg combination compared to amlodipine 10 mg monotherapy regimen in patients with moderate to severe hypertension. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Outpatients ≥18 years of age. 2. Patients with a diagnosis of moderate to severe hypertension, defined as msSBP ≥ 160 mmHg and < 200 mmHg at Visit 2. 3. 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. |
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E.4 | Principal exclusion criteria |
For full list, please refer to the protocol.
1. Patients previously treated in an aliskiren study that contained the treatment group of the combination of aliskiren and amlodipine and had been randomized or enrolled into the active drug treatment period of that study. 2. Severe hypertension defined as msSBP ≥ 200 mmHg and/or msDBP ≥ 120 mmHg. 3. Patients on a combination of 3 or more antihypertensive medications. Fixed combination of 2 drugs will be considered as 2 drugs. 4. Pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (≥ 5 mIU/ml). 5. 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 are using two birth control methods. The two methods can be a double barrier method (if accepted by local ethics committee) or a barrier method plus a hormonal method. • Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. Reliable contraception should be maintained throughout the study and for 7 days after the study. • 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 [for US only: and estradiol <20 pg/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. 6. History or evidence of a secondary form of hypertension. 7. Known Keith-Wagener grade III or IV hypertensive retinopathy. 8. Any history of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 12 months prior to Visit 1. 9. Previous or current diagnosis of heart failure (NYHA Class II-IV). 10. Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1. 11. Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based on the investigator’s clinical judgment. Patients with diabetes mellitus enrolled in this study should be well controlled. It is recommended that patients currently being treated for diabetes mellitus be on a stable dose of antidiabetic medication for at least 4 weeks prior to Visit 1. 12. Current angina pectoris requiring pharmacological therapy (use of nitrates for the treatment of angina will be allowed). 13. Second or third degree heart block without a pacemaker. 14. Atrial fibrillation or atrial flutter at Visit 1, or potentially life-threatening arrhythmia during the 12 months prior to Visit 1. 15. Clinically symptomatic valvular heart disease at 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 (Week 0) in mean sitting systolic blood pressure (msSBP). The primary analysis time point will be the 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 | 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 | 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) | 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 | No |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 24 |