A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis

Abstract

Background. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis.Methods. This was a multi-centre, open-label, randomized, crossover design study. Thirty-one haemodialysis patients were randomly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks.Results. The mean serum phosphorus was 1.6 ± 0.5 mmol/L (5.0 ± 1.5 mg/dL) during sevelamer carbonate powder treatment and 1.7 ± 0.4 mmol/L (5.2 ± 1.1 mg/dL) during sevelamer hydrochloride tablet treatment. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus; the geometric least square mean ratio was 0.95 (90% CI 0.87–1.03). No statistically significant or clinically meaningful differences were observed in calcium × phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets. Serum bicarbonate levels increased 2.7 ± 3.7 mmol/L (2.7 ± 3.7 mEq/L) during sevelamer carbonate treatment. No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment. Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study.Conclusions. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis. Bicarbonate levels improved only during sevelamer carbonate treatment. Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis.

A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis

“…2,3 In summary, both Genz-644470 and sevelamer carbonate effectively lowered hemodialysis patients' serum phosphorus levels in a dose-dependent fashion, but Genz-644470 did not show an advantage in phosphorus lowering in dialysis patients compared with sevelamer carbonate, as had been demonstrated by an in vitro assay. [6][7][8] Author contributions MM, contributing study investigator, contributed to multiple iterations of the manuscript text.…”

“…Previous studies of sevelamer have shown significant phosphate lowering within 1 week with small, incremental lowering at 2 weeks. 2,11,12 Therefore, the 3-week observation period employed in this study was considered of sufficient duration for an initial comparison of the efficacy of Genz-644470 and sevelamer carbonate in hemodialysis patients.…”

“…For patients on a Tuesday-Thursday-Saturday schedule, blood sampling took place on either a Thursday or Saturday. Precedent exists for brief study designs (or per agent crossover treatment periods) of a few weeks in phosphate binder studies 2,9 especially in Phase II 10 or dose-ranging designs. In addition, the majority of the phosphate-binding effect by a given dose of sevelamer hydrochloride, 11 sevelamer carbonate, 2,12 and other agents 13 has been observed to occur within 1 week, with a smaller, incremental effect observed at 2 weeks.…”

“…[1][2][3] Sevelamer is indicated in the United States and European Union for the control of hyperphosphatemia in dialysis patients; in Europe, it is also indicated for predialysis patients with serum phosphorus levels higher than 1.78 mmol/L (5.5 mg/dL). Nonadherence to phosphate binders, including sevelamer carbonate, is very common because of multiple factors, including dose frequency, resulting in a continued need for better phosphate control in the dialysis population.…”

Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD

“…In contrast to the earlier Cochrane review (8), sevelamer and CBBs did not differ significantly for end of study serum phosphate. Serum bicarbonate values were lower with sevelamer (hydrochloride and carbonate coanalyzed), likely reflecting the lower buffering capacity of sevelamer hydrochloride than Ca carbonate (46,47).…”