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 |
Evaluate the blood pressure lowering effect for the change from baseline to study endpoint in mean 24-hour systolic ambulatory blood pressure (ABPM) in patients ≥ 65 years of age with essential hypertension, by testing the hypothesis that 300 mg is superior to 75 mg |
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E.2.2 | Secondary objectives of the trial |
-Evaluate blood pressure lowering effect for change from baseline to study endpoint in mean 24-hour diastolic ambulatory blood pressure in patients ≥ 65 years with essential hypertension, by testing that 300 mg is superior to 75 mg. -Evaluate blood pressure lowering effects of aliskiren in patients ≥ 65 years with essential hypertension for change from baseline to study endpoint in mean sitting systolic and mean sitting diastolic office blood pressure. -Evaluate blood pressure lowering effects of aliskiren in patients ≥ 65 years with essential hypertension for change from baseline to study endpoint in mean day time systolic and diastolic ambulatory blood pressure. -Evaluate blood pressure lowering effects of aliskiren in patients ≥ 65 years with essential hypertension in mean night time systolic and diastolic ambulatory blood pressure. -Compare the blood pressure lowering effects of aliskiren and lisinopril. -Evaluate the safety and tolerability of aliskiren
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Outpatients ≥ 65 years of age and older. • Male or female patients are eligible. • Patients with essential hypertension. Patients must have an office cuff MSSBP ≥ 140 mmHg and <180 mmHg at Visit 2 or Visit 201 and an office cuff MSSBP ≥ 145 mmHg and < 180 mmHg at Visit 3. Patients must also have a baseline mean 24 hour systolic ABPM >135 mmHg at Visit 3. • Patients must have an absolute difference of 10 mmHg in their mean office cuff sitting systolic blood pressure (MSSBP) during the last two visits (Visit 2 and 3 or the optional Visit 201 and 3) of the single-blind placebo run-in period of the study. • 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 |
Patients with any of the following physiological states or concomitant medical conditions at either Visit 1, Visit 2, optional visit 201 or Visit 3 (unless otherwise stated) will be excluded from participation in the study. • Patients who previously entered an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. • Severe hypertension ( Office MSDBP ≥ 110 mmHg and/or Office 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 or previous diagnosis of heart failure (NYHA Class II-IV). • History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1. • Current angina pectoris requiring pharmacological therapy • Second or third degree heart block without a pacemaker. • Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. • Clinically significant valvular heart disease. • Type 1 or Type 2 diabetes mellitus with fasting glycosylated hemoglobin (HbA1c) > 8% at Visit 1. • Patients employed as a night shift worker. • Arm circumference <24 cm OR > 42 cm. • A diagnosis of Atrial Fibrillation • Serum sodium less than the lower limit of 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 X ULN at Visit 1 [ULN: male = 1.3 mg/dL (115 umol/L), female = 1.2 mg/dL (106 umol/l)], 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. • 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. • 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change from baseline in mean ambulatory 24-hour systolic blood pressure and the primary analysis time-point is the end of the study. |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |