E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus
Cardiovascular disease
Micro-albuminuria
Macro-albuminuria
Reduced estimated glomerular filtration rate
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus
Cardiovascular disease
Micro-albuminuria
Macro-albuminuria
Reduced estimated glomerular filtration rate
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027525 |
E.1.2 | Term | Microalbuminuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007648 |
E.1.2 | Term | Cardiovascular disease, unspecified |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018358 |
E.1.2 | Term | Glomerular filtration rate decreased |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 determine whether aliskiren, compared to placebo, when added to conventional treatment, delays the occurrence of cardiovascular and renal complications in patients with type 2 diabetes at high risk for cardiovascular and renal events.
For details on definition of cardiovascular or renal complications, please refer to the protocol. |
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E.2.2 | Secondary objectives of the trial |
• To determine whether aliskiren, compared to placebo, when added to
conventional treatment delays the occurrence of cardiovascular complications. For details on definition of cardiovascular complications, please refer to the protocol.
• To determine whether aliskiren, compared to placebo, when added to
conventional treatment delays the occurrence of renal complications. For details on definition of renal complications, please refer to the protocol.
Exploratory objectives:
For full list, please refer to the protocol.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Exploratory pharmacogenetic and mRNA expression profiling sub-study for CSPP100E2337.
A randomized, double-blind, placebo-controlled, parallelgroup study to determine whether, in patients with type 2 diabetes at high risk for cardiovascular and renal events, aliskiren, on top of conventional treatment, reduces cardiovascular and renal morbidity and mortality.
Objective: a) examining whether individual genetic variation in genes relating to drug metabolism, type 2 diabetes with renal and cardiovascular risk, and the drug target pathway confer differential response to aliskiren and b) examining the effect of aliskiren on gene expression in peripheral blood cells in type2 diabetic patients at risk for renal and cardiovascular disease
date : 26-Mar-2007
version of substudy: 1st version
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E.3 | Principal inclusion criteria |
-Type 2 diabetes and at least one of the following:
*Macroalbuminuria
*Microalbuminuria and a reduced kidney function
*Previous heart attack and a reduced kidney function
*Previous stroke and a reduced kidney function
*Heart Failure a reduced kidney function
*Coronary artery disease a reduced kidney function
- Concomitant treatment should follow national guidelines and must include either an Angiotensin-converting-enzyme-inhibitor (ACEi) or an Angiotensin-receptor-blocker (ARB) but not both
Other protocol-defined inclusion/exclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
- Type 1 diabetes mellitus
- Cardiovascular event or procedure ≤ 3 months prior to Visit 1
- Unstable serum creatinine
- Hypertension: Mean sitting systolic blood pressure (msSBP) ≥ 135 and < 170 mmHg or Mean sitting diastolic blood pressure (msDBP) ≥ 85 and < 110 mmHg unless treated with at least 3 antihypertensive medications
- Hypertension msSBP ≥ 170 or msDBP ≥ 110 mmHg
- Baseline Serum Potassium > 5.0 mmol/L
- Patients who are treated with two renin-angiotensin-aldosterone-system-blockers
- Patients with NYHA class III or IV heart failure
- Known renal artery stenosis
- Previous randomization into the AVOID trial (CSPP100C2201)
- Specific to the safety follow-up period: Aliskiren or aliskiren-containing fixed combination products must not be used in combination with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) in patients with diabetes.
- Specific to the safety follow-up period: Participation in another clinical trial, whether or not on investigational drug
Other protocol-defined inclusion/exclusion criteria may apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomization to the first event of the following composite endpoint:
Cardiovascular (CV) death
Resuscitated sudden death
Non-fatal myocardial infarction (MI)
Non-fatal stroke
Unplanned hospitalization for heart failure (HF)
Onset of end-stage renal disease (ESRD) defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
Doubling of baseline serum creatinine concentration to above the upper limit of normal according to the central laboratory, sustained for at least one month.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It will be calculated in days for each patient as the difference between the date of the first event or censoring date if no event occurs and the date of randomization visit (day 1) plus one. |
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E.5.2 | Secondary end point(s) |
Time from randomization to the first event of the following composite CV endpoint:
Cardiovascular (CV) death
Resuscitated sudden death
Non-fatal myocardial infarction (MI)
Non-fatal stroke
Unplanned hospitalization for heart failure (HF)
Time from randomization to the first event of the following composite renal endpoint:
Onset of end-stage renal disease (ESRD) defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
Doubling of baseline serum creatinine concentration to above the upper limit of normal according to the central laboratory, sustained for at least one month
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
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 | No |
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 | No |
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 | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 483 |
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 | No |
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 |
Argentina |
Austria |
Belgium |
Brazil |
Canada |
China |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Guatemala |
Hungary |
India |
Japan |
Korea, Republic of |
Lithuania |
Netherlands |
Norway |
Peru |
Portugal |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
Venezuela, Bolivarian Republic of |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Study duration is between 2.5 years and 5.5 years. This includes a safety long-term follow-up phase. Following the recommendation of the DMC overseeing the trial all patients were required to discontinue study drug by 6 Jan 2012. A 12 month safety follow-up period post study drug discontinuation is implemented upon request of CHMP. |
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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 | 4 |
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 | 4 |