| 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 |
| evaluate the overall safety of a regimen of aliskiren 150 mg potentially titrated to 300 mg O.D. with potential addition of hydrochlorotiazide (HCTZ) compared to a regimen of lisinopril 20 mg potentially titrated to 40 mg O.D. with potential addition of HCTZ in patients with uncomplicated severe hypertension (MSDBP ≥ 105 mmHg and < 120 mmHg) |
|
| E.2.2 | Secondary objectives of the trial |
• Evaluate blood pressure lowering effects of a regimen of aliskiren 150 mg potentially titrated to 300 mg O.D. with potential addition of HCTZ compared to a regimen of lisinopril 20 mg potentially titrated to 40 mg O.D. with potential addition of HCTZ in patients with uncomplicated severe hypertension (MSDBP ≥ 105 mmHg and < 120 mmHg).
• Evaluate proportion of patients achieving a successful response (MSDBP < 90 mmHg or a reduction ≥ 10 mmHg from baseline) for all treatment groups.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
• Outpatients 18 years of age and older.
• Male or female patients are eligible. Female patients must be either post-menopausal for at least one year, surgically sterile, or using effective contraceptive methods such as oral contraceptives, barrier method with spermicide or an intrauterine device.
• Patients with severe hypertension. Patients must have a MSDBP ≥85 mmHg and < 120 mmHg at Visit 2, and a MSDBP ≥105 mmHg and < 120 mmHg at Visit 3 (day 1, Randomization).
• 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 |
Patients with any of the following physiological states or concomitant medical conditions prior to randomization will be excluded from participation in the study.
• Patients who previously entered an aliskiren study and who qualified to be randomized or enrolled into active drug treatment period.
• History or evidence of a secondary form of hypertension, including but not limited to any of the following: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery sternosis, Cushing disease, pheochromocytoma, polycystic kidney disease.
• Patients on combination antihypertensive therapy that includes more than 3 classes of antihypertensive medication
• Diabetic patients requiring insulin treatment.
• Type 2 diabetics defined by fasting glycosylated hemoglobin (HbA1c) > 8% at Visit 1
• Known Keith-Wagener grade III or IV hypertensive retinopathy.
• History of hypertensive encephalopathy or cerebrovascular event to include stroke or transient ischemic cerebral attack (TIA).
• Previous or current diagnosis of heart failure of any class
• History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) at any time prior to Visit 1.
• Any type of angina pectoris (treated or untreated).
• Second or third degree heart block without a pacemaker.
• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
• Clinically significant valvular heart disease.
• Serum sodium less than the lower limit normal, serum potassium < 3.5 mEq/L or ≥ 5.5 mEq/L , or dehydration, 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 gastritis, 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 3 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 mg/dL (males) and > 1.3 mg/dL (females), a history of dialysis, or a history of nephrotic syndrome.
• Current treatment with cholestyramine and colestipol resins
• 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 angiotensin converting enzyme (ACE) inhibitor, thiazide diuretics, or other sulfonamide derived drugs.
• History of gouty arthritis.
• History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
• Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety.
• Participation in any investigational drug trial within one month of Visit 1.
• Persons directly involved in the execution of this protocol.
• Patients taking any concomitant medication listed in Section 6.5.4
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary assessment for safety is the overall adverse events percentage |
|
| 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 | No |
| 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) | 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 | 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 | 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.8.5 | 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 |
|
| 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
| |
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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