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

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.

Index Words: Sevelamer carbonate, sevelamer hydrochloride, once-daily dosing