E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
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 assess the effect of 3-month Sevelamer carbonate therapy compared to standard therapy on 24 h urinary protein excretion in patients with CKD and residual proteinuria despite optimized RAS inhibitor therapy |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of the study treatment on office blood pressure; GFR as assessed by iohexol plasma clearance; 24-h urinary phosphate, calcium, magnesium, urea, sodium and albumin excretion; phosphate, calcium, magnesium, urea, sodium and albumin fractional clearance; venous pH and base excess; serum levels of fibroblast growth factor (FGF) 23 (C terminal segment and the intact form) and other biomarkers of mineral metabolism including vitamin 25 OH D, 1-25 Vitamin D, calcium, phosphorous, intact parathyroid hormone (PTH), alkaline phosphatase (ALP); serum levels of markers of inflammation such as high sensitivity C Reactive Protein (hsCRP) and interleukin 6 (IL-6); serum lipids (total, HDL and LDL cholesterol and triglycerides); parameters of arterial stiffness such as pulse wave velocity (PWV) and augmentation index as assessed non invasively via applanation tonometry |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age > 18 years; - estimated GFR by simplified MDRD formula > 15 mL/min/1.73m2; - 24-h urinary protein excretion rate ≥ 0.5 g/24hour; - no concomitant treatment with phosphate binders; - written informed consent
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E.4 | Principal exclusion criteria |
- serum phosphate level < 2.5 or > 5.5 mg/dL; - serum PTH levels >250 pg/mL; - serum calcium level < 7.5 or >10.5 mg/dL; - history of congestive heart failure, myocardial infarction, cerebrovascular accident within the last 6 months; - cancer and any severe systemic disease or clinical condition that may jeopardize data interpretation or completion of the study; - presence of, or predisposition to, intestinal or ileus obstruction or severe gastrointestinal motility disorder (like severe constipation); - previous major gastrointestinal surgery; - previous kidney transplantation; - previous parathyroidectomy; - concomitant treatment with antiacid and phosphate binders with aluminium, magnesium, calcium or lanthanum; - concomitant treatment for secondary hyperparathyroidism with calcitriol, paracalcitriol and calcimimetic agents; - pregnancy or breastfeeding; - childbearing potential without reliable contraceptive methods during the whole study period; - participation in any clinical trial using an investigational product or device during the 30 days preceding the first protocol visit; - alcohol or drug (excluding tobacco) abuse ; - inability to comply with the study procedures during the whole study period, legal incapacity.
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E.5 End points |
E.5.1 | Primary end point(s) |
24-h urinary protein excretion (mean of three measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At begin and at the end of two treatment periods and at recovery visit.
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E.5.2 | Secondary end point(s) |
- office blood pressure; - GFR as assessed by iohexol plasma clearance; - 24-h urinary phosphate, calcium, magnesium, urea, sodium and albumin excretion; - phosphate, calcium, magnesium, urea, sodium and albumin fractional clearance; - venous pH and base excess; - serum levels of FGF 23 (C terminal segment and the intact form) and other biomarkers of mineral metabolism including vitamin 25 OH D, 1-25 Vitamin D, calcium, phosphorous, PTH, ALP; - serum levels of markers of inflammation such as hsCRP and IL-6; - serum lipids (total, HDL and LDL cholesterol and triglycerides); - parameters of arterial stiffness such as PWV and augmentation index as assessed non invasively via applanation tonometry.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At each visit except during the run-in period. |
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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 | No |
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) | 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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
double RAS inhibition therapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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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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 | 24 |
E.8.9.1 | In the Member State concerned days | |