A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis

作者：Fishbane Steven^*; Delmez James; Suki Wadi N; Hariachar Srinivas K; Heaton Jeremy; Chasan Taber Scott; Plone Melissa A; Moe Sharon

来源：American Journal of Kidney Diseases, 2010, 55(2): 307-315.

DOI：10.1053/j.ajkd.2009.10.051

• Sevelamer carbonate
• sevelamer hydrochloride
• once-daily dosing

Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing.
Study Design: Randomized parallel open-label study.
Setting & Participants: Hemodialysis patients.
Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets.
Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels.
Measurements: Serum phosphorus to 24 weeks.
Results: After washout, mean serum phosphorus level decreased 2.0 +/- 1.8 mg/dL (from 7.3 +/- 1.3 mg/dL) for sevelamer carbonate and 2.9 +/- 1.3 mg/dL (from 7.6 +/- 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder-treated patients and 64% of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (>= 3.5 and <= 5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal.
Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted.
Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative. Am J Kidney Dis 55: 307-315.

• 出版日期2010-2