| 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 |
|
| 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 |
|
| 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 phoshate 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 |
|
| 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.
to evaluate whether SBR759 is associated with less increase in serum iPTH levels compared to sevelamer HCl at 12 weeks
to evaluate whether SBR759 has an equivalent rate of hypercalcemia events at 12 weeks compared to sevelamer HCl as measured by serum calcium levels
to evaluate changes in patient-reported gasrointestinal symptom burden, using gastrointestinal symptom rating scale (GSRS) total and subscales scores, in patients treated with SBR759 compared to patients treated with sevelamer HCl |
|
| 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) |
|
| E.3 | Principal inclusion criteria |
1. Patients must give written informed consent before any assessment is performed.
2. Men or women of at least 18 years old.
3. Patient must be treated with a stable maintenance hemodialysis (i.e. no change in dialysis material and parameters) 3 times per week for > 3 months before screening and planned to be maintained the same throughout the study duration.
4. Patient must be on restricted phosphate diet at screening and throughout the study.
5. Patient has a controlled serum phosphate > 3.0 mg/dL (> 0.97 mmol/L) and < 6.0 mg/dL (< 1.9 mmol/L), as indicated by the average of the 2 latest pre-dialysis laboratory values reported prior to screening, if currently under phosphate binder therapy.
6. Patient has a serum phosphate level > 6.0 mg/dL (> 1.9 mmol/L), obtained from central laboratory, prior to study treatment initiation.
7. Patient must have a Urea Reduction Ratio of > 65% (obtained within 2 weeks prior to screening).
8. If patient has a history of parathyroidectomy, iPTH and calcium-phosphate product levels should be stable within 30 days prior to screening.
9. Patient must be on a stable phosphate binder dose (i.e. No change in prescribed dose) for at least 30 days prior to screening, or is newly diagnosed with hyperphosphatemia and has not initiated treatment with phosphate binder yet.
10. Patient must, in the investigator’s opinion, be compliant with prescribed phosphate binders.
11. If patient is currently being treated with calcimimetics, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
12. If patient is currently being treated with vitamin D, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
13. If patient is currently being treated with IV iron, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
14. If patient is currently being treated for osteoporosis, the prescribed dose must be constant for at least 30 days prior to screening and during the total core study duration.
|
|
| E.4 | Principal exclusion criteria |
1. Patient is on peritoneal dialysis or a non-conventional hemodialysis technique (e.g.
hemofiltration, hemodiafiltration)
2. Patient has a parathyroidectomy or transplant scheduled during the study.
3. Patient has an uncontrolled hyperparathyroidism (i.e. intact PTH > 800 pg/mL within 30 days prior to study screening)
4. Patient has a history of hemochromatosis or ferritin > 800 μg/L.
5. Patient has a clinically significant GI disorder (i.e. swallowing disorder, active dysphagia, bowel obstruction, severe GI motility disorder)
6. Patient has a chronic unstable GI disorder (e.g. Irritable Bowel Syndrome, Inflammatory Bowel Disease, chronic abdominal pain, chronic diarrhea)
7. Patient has an history of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection.
8. Patient has a clinically significant unstable medical condition (e.g. uncontrolled diabetes, etc.), other than Chronic Kidney Disease.
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
10. Patient is known to currently have a drug or alcohol abuse problem.
11. Patient has a known history of immunodeficiency disease, e.g. existing positive HIV (ELISA or Western blot) test result.
12. Patient is / has been treated with sevelamer HCl monotherapy or SBR759 within 3 months prior to screening.
13. History of intolerance to sevelamer HCl.
14. Patient is currently being treated with oral iron.
15. Patient currently has an active infection or is being treated with antibiotics (within 14 days prior to screening).
16. Patient currently has an active antiviral treatment for Hepatitis B and/or C (within 30 days prior to screening).
17. Patient is currently being treated with anti-seizure medications for the control of a seizure disorder (i.e. phenobarbital, valproate, carbamazepine)
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer
19. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
20. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation
21. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To demonstrate superior efficacy or at least non-inferiority of SBR759 compared to sevelamer HCl, as 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. |
|
| 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 |
|
| 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) |
|
| 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
| 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 | 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 |
|
| 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
|
| 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 |
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