E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with hypertension, Type 2 DM and proteinuria |
|
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 objective of this study is to: • Demonstrate the efficacy of aliskiren on proteinuria when added to standardized losartan therapy (100mg OD) and optimal antihypertensive therapy in patients with hypertension and Type 2 DM by testing the hypothesis of superior reduction in proteinuria (% reduction in UACR) from baseline to study end when compared to placebo.
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to: • Evaluate the proportion of patients who have their UACR reduced by ≥ 50% from baseline to study end. • Evaluate the effect of aliskiren on UAER from baseline to study end. • Evaluate the effect of aliskiren on MSSBP and MSDBP in this patient population. • Evaluate the effect of aliskiren 150 mg OD versus forced titration to aliskiren 300 mg OD on urinary albumin/creatinine ratio reductions by comparing month 3 to month 6. • Evaluate the safety and tolerability of aliskiren in this patient population. • Explore the impact of treatment on biomarkers as compared to baseline. • Explore the effects of aliskiren on GFR. • Explore the effect of aliskiren on QoL as assessed by the Psychological General Well-Being Index (PGWBI)
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects eligible for inclusion in this study are: • Outpatients 18 years of age to 75. • 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 with hypertension (currently treated with antihypertensive medication(s) or MSSBP > 140 mmHg or MSDBP > 90 mmHg) at Visit 1. • Urine dipstick for protein ≥ trace at Visit 1. • Proteinuria as defined by a spot urine specimen collection at Visit 1 (UACR ≥ 300mg/g and ≤ 3500 mg/g). • Proteinuria demonstrated in 2 of 3 early morning void spot urine specimen collections at Visit 5 or Optional Visit 501 (UACR ≥ 100 mg/g and ≤ 3500 mg/g.). • MSSBP <150 mmHg and MSDBP < 95 mm Hg at Visit 5 (or optional Visit 501), and at Visit 6. • Patients must be on stable concomitant antihypertensive medications for at least 2 weeks prior to Visit 6. • Patients must be on stable hypoglycemic medications for at least 4 weeks prior to Visit 6. • Patients must be willing and medically able to discontinue all ACEI, ARB (other than Novartis supplied losartan), aldosterone receptor antagonist and potassium sparing diuretic medications for the duration of the study. • Patients must be willing and medically able to take losartan 100 mg OD for the duration 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)
|
|
E.4 | Principal exclusion criteria |
• Patients who previously participated in any aliskiren study. • Severe hypertension (grade 3 WHO classification; MSSBP 180 mmHg and/or MSDBP 110 mmHg). • Kidney disease not caused by diabetes or hypertension. • History of chronic urinary tract infections (UTI) • Serum potassium < 3.5 or > 5.1 mEq/L. • GFR < 40 ml/min/1.73m2 as measured by the MDRD formula. • Serum albumin < 2.0mg/dL. • History of hypertensive encephalopathy or cerebrovascular accident at any time prior to Visit 1. • Transient ischemic cerebral attack during the 6 months prior to Visit 1. • Current diagnosis of heart failure (NYHA Class II-IV). • History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1. • Second or third degree heart block without a pacemaker. • Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. • Clinically significant valvular heart disease. • Type 1 diabetes mellitus. • Uncontrolled Type II diabetes mellitus (HbA1C >11 %) • 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 2 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. • Current obstruction of the urinary tract or difficulty in voiding due to mechanical or inflammatory conditions which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator. • 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 or allergy to angiotensin receptor blockers
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is % change from baseline in urinary albumin/creatinine ratio (mg/g), calculated as 100*(post value – baseline)/baseline (%). |
|
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 | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned days | |