E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hyperphosphataemia in patients with Chronic Kidney Disease (CKD) on hemodialysis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
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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 |
This study is designed to demonstrate superior or at least non-inferior efficacy of SBR759 in phosphate binding, versus sevelamer HCl and evaluate safety over a long term exposure. Efficacy will be measured by the number of patients with a serum phosphate level below or equal to 5.5 mg/dl (i.e. 1.78 mmol/L) at 12 weeks |
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E.2.2 | Secondary objectives of the trial |
To evaluate safety and tolerability of SBR759 compared to sevelamer HCl over a 12-week period. To evaluate whether SBR759 has superior efficacy at week 12 compared to sevelamer HCl, as measured by the number of patients with a serum calcium-phosphate product levels below or equal to 55 mg2/dL2. |
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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 |
Assessments subjects to an additional informed consent form but included in the main protocol: - phosphate dynamics during dialysis (evaluation of phosphate levels removed during dialysis in all patients and validation of Gutzwiller formula in 12 patients) - Imaging and Pulse Wave Velocity procedure (evaluation of changes in bone metabolism and vascular calcification in 50 patients) |
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E.3 | Principal inclusion criteria |
Men or women of at least 18 years old. Patient must be ON maintenance RENAL REPLACEMENT THERAPY (I.E. hemodialysis, HEMOFILTRATION OR HEMODIAFILTRATION) Patient must be on restricted phosphate diet at screening and throughout the study. IF CURRENTLY UNDER PHOSPHATE BINDER THERAPY patient has a controlled serum phosphate > 3.0 mg/dL (> 0.97 mmol/L) and ≤ 6.5 mg/dL (≤2.1 mmol/L) AS INDICATED BY SINGLE VALUE OBTAINED FROM THE CENTRAL LABORATORY AT SCREENING (I.E. OBTAINED AT A 72 HR POST-DIALYSIS INTERVAL) Patient has a serum phosphate level ≥ 6.0 mg/dL (≥ 1.9 mmol/L) OBTAINED AT A 72 HR POST-DIALYSIS INTERVAL) FROM A CENTRAL LABORATORY PRIOR TO RANDOMISATION AND TREATMENT INITIATION 9I.E. AFTER 2 WEEKS WASHOUT IF NO EXEMPTION IS APPLICABLE. Patient must have a Urea Reduction Ratio of > 60% (obtained FROM A CENTRAL LABORATORY AT screening) Patient must be on a stable phosphate binder dose OR HAVE NOT RECEIVED PHOSPHATE BINDER THERAPY FOR AT LEAST 4 WEEKS PRIOR TO SCREENING. |
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E.4 | Principal exclusion criteria |
Patient is on peritoneal dialysis Patient has a parathyroidectomy WITHIN 3 M PRIOR TO SCREENINGor transplant scheduled during the study. Patient has an uncontrolled hyperparathyroidism OBTAINED FROM A CENTRAL LABORATORY AT SCREENING Patient has a history of hemochromatosis or serum ferritin > 1000 800 μg/L OBTAINED FROM CENTRAL LABORATORY AT SCREENING. Patient has a clinically significant GI disorder Patient has a chronic unstable GI disorder Patient has an history of major gastrointestinal tract surgery History of intolerance to sevelamer HCl. Patient is currently being treated with oral iron. PATEINT IS TREATED WITH OSTEOPOROSIS TREATMENT WITHIN 30 DAYS PRIOR TO SCREENING PATIENT HAS A TRANSFERRIN SATURATION >60% OBTAINED FROM CENTRAL LAB AT SCREENING. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients with a serum phosphate level below or equal to 5.5 mg/dL (1.78 mmol/L) |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
change in bone metabolism and vascular calcification biomarkers; dynamics of phosphate levels in HD |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 |
Stratified per serum phosphorus levels (<or>= to 75.mg/dL) |
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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 | No |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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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The trial will be considered completed after completion of the extension study, including the 2 weeks random treatment withdrawal period. |
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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 | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 13 |