FP405EFFICACY AND SAFETY OF SEVELAMER CARBONATE IN HYPERPHOSPHATEMIC PATIENTS WITH CHRONIC KIDNEY DISEASE ON HEMODIALYSIS AND NON-DIALYSIS: A PROSPECTIVE, OPEN-LABEL, DOSE-TITRATION STUDY IN RUSSIA

Abstract

Introduction and Aims: Reducing hyperphosphatemia and maintaining the serum phosphorus (sPO4) level within normal range is an important therapeutic target which contributes to improvement of clinical outcomes in patients with chronic kidney disease (CKD) 4-5D stages. The goal of this study was to assess the sPO4 reduction in hemodialysis and non-dialysis CKD patients treated with sevelamer carbonate (SC) in drug formulation of either tablets or powder. Methods: Prospective, open-label, non-comparative, multicenter, dose-titration, phase III study was conducted to evaluate serum phosphorus (sPO4) reduction from baseline in hemodialysis and non-dialysis CKD patients treated with SC in form of either tablets (800 mg SC), or powder (2.4 g SC in sachet) for 8 weeks. Patients were eligible for inclusion, if their sPO4 was 1.78 mmol/l or higher at baseline. 48 dialysis and 48 non-dialysis patients (96 patients in total) were randomized to receive SC (either tablets or powder). Starting dose was defined individually and based on baseline sPO4 level: 2.4 g per day for patients with sPO4 level ranged from 1.78 to 2.42 mmol/l and 4.8 g per day for patients with sPO4 level > 2.42 mmol/l. Dose titration was performed as follows: increase of daily dose by 2.4 g (3 tabs or 1 sachet) if the sPO4 remained higher than 1.78 mmol/l on any subsequent visit (up to maximum daily dose of 12g). Results: In total patients population (mITT-analysis) mean absolute reduction rate for sPO4 was 0.50 mmol/l [95%CI 0.38-0.62], p=0.0001; relative reduction rate-19.8% [95%CI 15.5-24.04] from baseline. Considering hemodialysis patients, mean sPO4 decreased by 0.62 mmol/l [95%CI 0.36-0.88], p=0.0001 and by 0.66 mmol/l [95%CI 0.39-0.93] p=0.0001 vs baseline in those treated with SC powder and SC tablet respectively. Results obtained in non-dialysis patients: mean sPO4 decreased by 0.27 mmol/l [95%CI 0.06-0.48] p=0.014 and by 0.41 mmol/l [95%CI 0.2-0.62] p=0.001 vs baseline in those treated with SC powder and SC tablet respectively. Adverse events (AE) were reported in 11 patients (11,4%). No serious adverse events occurring during the study were considered to be related to the intervention. 10 of 96 patients (10,4%) discontinued the study prematurely (2 due to adverse events, 8-reason unknown). Conclusions: Significant reduction of serum phosphorus was demonstrated in hemodialysis and non-dialysis patients with chronic kidney disease treated with seve-lamer carbonate tablets or powder.