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

Abstract

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 (> or =3.5 and < or =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.

Trial registration: ClinicalTrials.gov NCT00324376.