E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hyperphosphataemia in chronic kidney disease patients on renal replacement therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020711 |
E.1.2 | Term | Hyperphosphataemia |
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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 evaluate the change from baseline in 72-hour serum phosphate levels of different doses of SBR759 versus placebo over 4 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate changes in serum phosphate during a 2-week random treatment withdrawal period of SBR759 after 4 weeks treatment; To evaluate dose-dependent efficacy of SBR759; To compare the short-term safety profile and dose-dependent tolerability of SBR759, dosed TID with meals, to that of placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Men or women of at least 18 years of age willing to provide informed consent. 2.Patient must be on maintenance renal replacement therapy (i.e. hemodialysis, hemodiafiltration or hemofiltration) 3 times per week for ≥ 3 months and must be treated with a stable dialysis prescription, as defined by no change in material (filter/membrane) and dialysis duration (≥ 3 hours) for ≥ 4 weeks before screening and planned to be maintained the same throughout the study duration. 3.Patient must be on a stable phosphate binder dose (i.e. no change in prescribed dose), and willing to stop their phosphate binder therapy at start of screening to enter the 2-week wash-out period, or not have received any phosphate binder therapy for at least 4 weeks prior to screening. 4. At Screening visit and if currently under phosphate binder therapy, patient has a controlled serum phosphate level > 0.97 mmol/L (> 3.0 mg/dL) and ≤ 2.1 mmol/L (≤ 6.5 mg/dL), obtained from central lab. 5. At Baseline visit, Patient has a serum phosphate level > 1.78 mmol/L (> 5.5 mg/dL) and ≤ 2.9 mmol/L (≤ 9.0 mg/dL), obtained at a 72-hour post-dialysis interval, from the local laboratory, prior to randomization and study treatment initiation. 6. Patient must have a Kt/V ≥ 1.2, obtained from local lab, or Urea Reduction Ratio ≥ 60%, obtained from central lab, at screening. 7. Patients receiving active Vitamin D must be on stable dose at screening and planned to be maintained stable throughout the study duration. 8. Patients receiving calcimimetics must be on stable doses for at least 4 weeks prior to screening and planned to be maintained stable throughout the study duration. 9. Patient must be on phosphate restricted diet at screening and throughout the study. 10. Patient should be compliant with prescribed medications, in the opinion of the investigator. |
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E.4 | Principal exclusion criteria |
1. Patient is on peritoneal dialysis; 2. Patient has a transplant scheduled during the study; 3. Patient has an uncontrolled hyperparathyroidism (i.e. intact PTH > 84.8 pmol/L (> 800 pg/mL), obtained from central laboratory at screening); 4. Patient had a parathyroidectomy within 3 months prior to screening or for more than 3 months and iPTH < 2.65 pmol/L (< 25 pg/mL) obtained from central laboratory at screening; 5. Patient has a parathyroidectomy scheduled during the study; 6. Patient has a clinically significant (e.g. chronic unstable) GI disorder and/or has an history of major gastrointestinal tract surgery (e.g. gastrectomy, extensive bowel resection); 7. Patient has a history of hemochromatosis or serum ferritin > 1000 ng/mL, obtained from central lab at screening; 8. Patient has a transferrin saturation > 60%, obtained from central lab at screening; 9. Patient has a clinically significant unstable medical condition (in the opinion of the investigator), other than Chronic Kidney Disease that could negatively impact adequate study conduct/participation; 10. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years; 11. Patient is known to currently have a drug or alcohol abuse problem; 12. Patient has a known history of immunodeficiency disease, e.g. existing positive HIV (ELISA or Western blot) test result; 13. Patient is currently being treated with oral iron; 14. Patient is treated with bisphosphonates for osteoporosis treatment within 30 days prior to screening; 15. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer; 16. History of hypersensitivity to the study drug or to drugs of similar chemical class; 17. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation; 18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the change from baseline in 72-hour serum phosphate levels of different doses of SBR759 versus placebo over 4 weeks of treatment. |
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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 | No |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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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vedere sezione 6.5.9 del Protocollo |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |