E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cardiovascular disease in chronic kidney disease |
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E.1.1.1 | Medical condition in easily understood language |
Heart- and vesseldiseases in patients with kidney failure. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 demonstrate the feasibility to induce an effective, predictable and sustained decrease in FGF23 level in CKD stage I-IV patients, without inducing hypophosphatemia using a stepped treatment regimen aiming at restricting phosphate uptake. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with stage II-IV CKD or with stage I CKD with an albumin-to-creatinine ratio in a first morning spot urine specimen of 100 mg/mmol, while on ACE-inhibition or on ARBs. 2. Serum phosphate levels between 0.80-1.45 mmol/l. 3. Not taking any phosphate binder therapy. 4. Providing informed consent. Inclusion will be stratified according to stage CKD according to the National Kidney Foundation.
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E.4 | Principal exclusion criteria |
1. Patients who, in the opinion of the study investigator may present a safety risk. 2. Patients who are unlikely to adequately comply with the trial’s procedures (due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or noncompliance). 3. Patients taking medications or having concomitant illnesses likely to confound endpoint assessments (e.g. phosphate binder therapy, antiarrhythmic agents or anticonvulsants). 4. Patients with albumin-to-creatinine ratio > 100 mg/mmol not receiving ACE-inhibitors or ARB. 5. Patients with LDL-cholesterol >2.5 not receiving statin therapy. 6. Patients taking other experimental (i.e., non marketed) therapies. 7. Women, who are pregnant or breastfeeding. 8. Unwillingness to comply with reproductive precautions. Women who are capable of becoming pregnant must be willing to comply with approved birth control from two-weeks prior to, and for 60 days after taking investigational product. 9. Change in vitamin D dose 4 weeks prior to baseline. 10. History of hyperparathyroidism or parathyroidectomy. 11. History of arrhythmia or seizures. 12. Patients who have bowel obstruction, or malabsorption. 13. Posttransplant patients. 14. Allergy or intolerance for study medication. 15. Body mass index > 35 16. History of ADPKD
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E.5 End points |
E.5.1 | Primary end point(s) |
1) To demonstrate the absolute (reference unit per ml) and percentage change in C-terminal FGF-23 (Immutopics) in the highest tolerable dose of sevelamer compared to baseline for each stage of CKD. 2) To demonstrate the dose response relationship between C-terminal FGF-23 and sevelamer dose of the entire cohort.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the study is completed, so after 18 weeks. |
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E.5.2 | Secondary end point(s) |
The following explorative variables will be assessed: plasma levels of creatinine, phosphate, albumin, calcium, 25(OH)2D and 1,25(OH)2D3 and PTH. Urine: 24 hours phosphate excretion, TmP/GFR and albuminuria. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 ends when all the patients completed the trialperiod. |
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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 | |
E.8.9.1 | In the Member State concerned days | |