| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
| Demonstrate the efficacy of the combination therapies of aliskiren/amlodipine (150/10 mg and 300/10 mg), in hypertensive patients who do not adequately respond to a 4-week treatment of amlodipine 10 mg by testing the hypothesis of superior reduction in mean sitting diastolic blood pressure (msDBP) from baseline to end of study when compared to amlodipine 10 mg monotherapy. |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary objectives are listed below. For full list, please refer to the protocol.
• Evaluate the efficacy of the combination therapies of aliskiren /amlodipine (150 / 10 mg and 300/10 mg) in hypertensive patients who do not adequately respond to a 4-week treatment of amlodipine 10 mg, by testing the hypothesis of superior reduction in mean sitting systolic blood pressure (msSBP) from baseline to end of study when compared to amlodipine 10 mg monotherapy.
• Evaluate the safety and tolerability of the combinations of aliskiren /amlodipine (150/10 mg and 300/10 mg) compared, with amlodipine 10 mg monotherapy in hypertensive patients who do not show an adequate blood pressure response to a 4-week treatment of amlodipine 10 mg.
• Evaluate the proportion of patients achieving a blood pressure control target of < 140 / 90 mmHg at the end of study for all treatment arms.
• Assess whether the combinations of aliskiren/amlodipine attenuate amlodipine induced edema. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Outpatients 18 years of age and older.
2. Male or female patients are eligible.
3. Patients with a diagnosis of hypertension:
• Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a msDBP ≥ 95 mmHg and < 110 mmHg at Visits 1 and 2.
• Patients who have been treated for hypertension within the 4 weeks prior to Visit 1 must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 2.
• All patients must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 5.
4. 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). |
|
| 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 (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).
3. 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).
4. 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 ethnics 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.
5. History or evidence of a secondary form of hypertension.
6. Known Keith-Wagener grade III or IV hypertensive retinopathy.
7. Any history within 12 months prior to Visit 1 of the following: hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
8. Previous or current diagnosis of heart failure (NYHA Class II-IV).
9. Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1.
10. 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 Visit 1.
11. Current angina pectoris requiring pharmacological therapy (use of nitrates for the treatment of angina will be allowed).
12. Second or third degree heart block without a pacemaker, or potentially life-threatening arrhythmia during the 12 months prior to Visit 1.
13. 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 (Visit 5) in mean sitting diastolic blood pressure (msDBP). The primary analysis timepoint is end of study using last observation carried forward as defined in Section 10.4.3 referred to as the Endpoint measurement. |
|
| 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) | 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 | 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 |
|
| 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 |
|
| 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 | 50 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 112 |
| 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 |
|
| 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
| |
| 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 | |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 22 |
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