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 |
To assess the long term safety of the combination of aliskiren / amlodipine / hydrochlorothiazide in patients with essential hypertension over 28 week to 54 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
• To assess the long-term blood pressure lowering (msDBP and msSBP) efficacy of the combination of aliskiren / amlodipine / hydrochlorothiazide in patients with essential hypertension • To evaluate the proportion of patients achieving the blood pressure control target of < 140/90 mmHg at the end of the study. • To evaluate the proportion of patients achieving a response in mean sitting diastolic blood pressure (msDBP < 90 mmHg or a ≥ 10 mmHg decrease from baseline) and mean sitting systolic blood pressure (msSBP < 140 mmHg or a ≥ 20 mmHg decrease from baseline) at the end of study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Outpatients 18 years of age or older 2. Male or female patients are eligible. 3. msDBP & msSBP Requirements: • For newly diagnosed/untreated patients, msDBP ≥ 100 and < 120 mmHg, and/or msSBP ≥ 160 and < 200 mmHg at Visit 1 and Visit 2. • For previously treated patients, msDBP 100 and < 120 mmHg, and/or msSBP ≥ 160 and < 200 mmHg at Visit 2, Visit 3, or Visit 4. • For patients requiring tapering off their previous antihypertensive medication, they must meet the above criteria and completely discontinue all antihypertensive treatment prior to entering the treatment phase of the study. 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). |
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E.4 | Principal exclusion criteria |
For full list, please refer to the protocol.
1. Inability to discontinue all prior antihypertensive medications safely for a period of 1 to 4 weeks as required by the protocol. 2. Patients on three antihypertensive drugs with msDBP ≥ 110 mmHg and/or msSBP 180 mmHg at Visit 1. 3. Patients on four or more antihypertensive drugs at Visit 1. 4. Patients with an msSBP 200 and msDBP 120 mmHg anytime during the washout period of the study Visit 1-4 must be discontinued from the study. 5. 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). 6. 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 following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation) or hormonal contraception (e.g., implantable, patch, oral). Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 7. History or evidence of a secondary form of hypertension. 8. Any history of hypertensive encephalopathy, cerebrovascular accident, heart failure, transient ischemic cerebral attack (TIA), angina pectoris, myocardial infarction (MI), coronary bypass surgery, or any percutaneous coronary intervention (PCI). 9. Serum potassium <3.5 mEq/L (mmol/L) or > 5.5 mEq/L at Visit 1. 10. Patients Type 2 diabetes mellitus (DM) who are not well controlled based on the investigator's clinical judgment. Patients with Type 2 DM enrolled in this study should be well controlled. It is recommended that patients currently being treated for Type 2 DM be on a stable dose of oral antidiabetic medication for at least 4 weeks prior to Visit 1. Type 1 DM patients are excluded. 11. Second or third degree heart block with or without a pacemaker, or other potentially lifethreatening or symptomatic arrhythmia current or by history. 12. Atrial fibrillation or atrial flutter during the screening period. 13. Clinically significant valvular heart disease. 14. Any medication, surgical, or medical condition, which might significantly alter the absorption, distribution, metabolism, or excretion of medications including but not limited to any of the following: • History of major GI tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. • History of active inflammatory bowel disease during the 12 months prior to Visit 1. • Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal bleeding during the 3 months prior to Visit 1. • Current treatment with cholestyramine or colestipol resins. 15. Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary assessment for safety is the reporting of any adverse events and serious adverse events (SAE) including death, discontinuations due to adverse events, and abnormal laboratory data. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
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
| 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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 | |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |