| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of essential hypertension |
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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 |
The primary objectives of this study are to:
• Confirm the efficacy of aliskiren 75 mg, 150 mg and 300 mg in patients with essential hypertension by testing the hypothesis of superior reduction in MSDBP from baseline to study end when compared to placebo.
• Demonstrate the efficacy of the combination of aliskiren and HCTZ 75/6.25 mg, 75/12.5 mg, 150/6.25 mg, 150/12.5 mg, 150/25 mg, 300/12.5 mg and 300/25 mg in patients with essential hypertension by testing the hypothesis of superior reduction in MSDBP from baseline to study end when compared to the component monotherapies.
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| E.2.2 | Secondary objectives of the trial |
• Demonstrate the antihypertensive dose response effect of aliskiren alone and in combination with HCTZ by testing the hypothesis that the magnitude of MSDBP and MSSBP reduction are related to the dose level of aliskiren and HCTZ administered in this study population.
• Explore the safety and tolerability of aliskiren 75 mg, 150 mg and 300mg, given alone and in combination with HCTZ, in patients with essential hypertension.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
• Patients with essential hypertension. Patients must have a MSDBP ≥90 mmHg and<100 mmHg at the visit prior to Visit 3 (Visit 2 or optional Visit 201), and a MSDBP ≥95 mmHg and <110 mmHg at Visit 3 (day 1).
• Patients must have an absolute difference of ≤10 mmHg in their average sitting diastolic blood pressure during the last two visits (Visit 2 and 3 or the optional visit 201 and 3) of the single-blind lead-in period of the study.
• Outpatients 18 years of age and older
• 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 spermicide or an intrauterine device.
• 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 have been clearly explained to them (written informed consent).
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| E.4 | Principal exclusion criteria |
• Patients previously treated with aliskiren
• Severe hypertension (grade 3 WHO classification; MSDBP ≥110 mmHg and/or MSSBP ≥180 mmHg).
• History or evidence of a secondary form of hypertension
• Known Keith-Wagener grade III or IV hypertensive retinopathy.
• History of hypertensive encephalopathy or cerebrovascular accident
• Transient ischemic cerebral attack during the 12 months prior to Visit 1.
• Current diagnosis of heart failure (NYHA Class II-IV)
• History of myocardial infarction, coronary bypass surgery, or any percutaneaous coronary intervention (PCI) during the 12 months prior to Visit 1.
• Current angina pectoris requiring pharmacological therapy (other than sublingual nitroglycerin).
• Second or third degree heart block without a pacemaker.
• Concurrently potentially life threatening arrhythmia or symptomatic arrhythmia.
• Clinically significant valvular heart disease.
• Type 1 or Type 2 diabetes mellitus with poor glycemic control defined as fasting glycosylated hemoglobin (HbA1c) >9% at Visit 1.
• Serum sodium and/or serum potassium less than the lower limit of normal, dehydration, or hyperkalemia ≥5.5 mEq/L at Visit 1.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following:
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
• Currently active or previously active inflammatory bowel disease during the 12 months prior to Visit 1.
• Currently active gastritits, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1.
• Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
• Evidence of hepatic disease as determined by any one of the following: SGOT or SGPT values exceeding 2 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt.
• Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome.
• History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the past five years.
• History or evidence of drug or alcohol abuse within the last 12 months.
• Pregnant or nursing women.
• Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
• Known or suspected contraindications to the study medications, including history of allergy to thiazide diuretics or other sulfonamide derived drugs.
• History of gouty arthritis.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is change from baseline (Visit 3) in mean sitting diastolic blood pressure. The primary analysis will be conducted in change from baseline to the end of study (endpoint). For each patient, the last post-baseline measurement during the double-blind period will be carried forward as the endpoint measurement for the variable to be analyzed. |
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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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 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.8.5 | 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 | Information not present in EudraCT |
| 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 | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
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