E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease is characterized by a progressive decline of glomerular filtration rate (GFR), which occurs irrespectively of the cause of the renal damage once a critical nephron mass has been lost. |
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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 |
To evaluate the efficacy, safety and tolerability of valsartan versus placebo in children with Chronic Kidney Disease (CKD) manifested by persistent proteinuria (> 500 mg/g) while receiving a standardized dose of ACEI therapy to provide important prescribing information to the pediatrician on the use of valsartan in children with CKD. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the proportion of patients who have their UPCR reduced by ≥ 50% from baseline to end of Period 1. • Evaluate the proportion of patients who have their urine albumin/creatinine ratio (UACR) reduced by ≥ 50% from baseline to end of Period 1. • Evaluate proteinuria reduction as measured by UACR from baseline to end of Period 1 Entire study : To Evaluate: • Proportion of patients who have their UPCR reduced by ≥ 50% from baseline to end of Period 2. • Proportion of patients who have their urine albumin/creatinine ratio (UACR) reduced by ≥ 50% from baseline to end of Period 2. • Proteinuria reduction as measured by UPCR and UACR from baseline to end of Period 2. • Proportion of patients with ≥ 25% GFR loss from baseline at end of Period 2. • Change in GFR (difference in slope) from baseline to end of treatment Period 2. • To evaluate the overall safety and tolerability of valsartan in this population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(For Full list, see protocol) • Pediatric outpatients, 5-17 years of age, with a history of chronic kidney disease. • Male and female patients with body weight ≥ 15 kg and ≤ 100 kg are eligible. • Must be able to swallow tablets. • Must be receiving a standardized dose of an ACEI for at least for 2 months, for the treatment of proteinuria, without known ACEI-suspected adverse effects which could prevent the patient from continuing to receive the same dose of the ACEI for an additional 18 months. • Urine dipstick for protein ≥ trace at Visit 1. • Proteinuria demonstrated in 2 of 3 early morning void urine specimen collections at Visit 2 (UPCR ≥ 500 mg/g). • GFR ≥ 30 ml/min/1.73m2 and ≤ 90 ml/min/1.73m2, as estimated by the Schwartz formula using the Visit 1 serum creatinine value. • MSSBP/MSDBP must be < 95th percentile, for age, gender and height, at Visit 2, by office blood pressure measurement. |
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E.4 | Principal exclusion criteria |
(For full list, see protocol): Renal transplant patients • Renal artery stenosis. • Patients with active systemic disease(s) (e.g. diabetes, amyloidosis, vasculitis, lupus nephritis) defined as those with current, recent (in the past two months) or frequent (≥ 2 episodes in the past 12 months) exacerbations of disease activity, and those in whom immunosuppressive medication was increased within two months prior to screening • Patients who are currently or within two months prior to screening on the following medications. [Note: Patients on maintenance immunosuppressive therapy (CsA, FK 506, MMF or azathioprine), administered at unchanged dose in the past 2 months pior to screening, and expected to remain unchanged throughout the study, are allowed.]: • Intraveous or oral cyclophosphamide • Intravenous or oral steroid pulse therapy • Oral steroid therapy >0.5 mg/kg/d • Serum potassium < 3.5 or > 5.3 mEq/L. • Hemoglobin < 8 gm/dL. • WBC < 3000/mm3. • Patients currently on Angiotensin II type-1 Receptor Blocker (ARB) therapy • Patients are not medically able or willing to discontinue aldosterone receptor antagonist and/or potassium sparing diuretic medications for the duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Period 1 : Change from baseline in log (UPCR) month 4
Period 1 + Period 2 : Chronic slope of GFR over time, month 2 to 18 |
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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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 8 |