Sevelamer carbonate (SC), a non-calcium based phosphate binder, is safe and effective for decreasing serum phosphorus levels in children and adolescents with hyperphosphatemia, results of a phase 2 placebo-controlled study shows.
“Sevelamer carbonate has been used for the management of hyperphosphatemia in the pediatric population for some time,” lead investigator Brad Warady, MD, of Children’s Mercy Kansas City in Kansas City, Missouri, told Renal & Urology News. “This placebo-controlled trial provides definitive evidence of its safety and efficacy when used in children.”
At the time of the study, no phosphate binders had been approved by the FDA for use in pediatric patients, he and his colleagues stated.
After a washout period from previous phosphate binders, Dr Warady and his team randomly assigned 101 pediatric patients with chronic kidney disease (74% adolescents; mean age 14.1 years; 77% on dialysis) from 29 centers in the United States and Europe to sevelamer carbonate or placebo at fixed doses based on body surface area. After the 2-week fixed-dose period, all patients received the drug for 6 months, at doses titrated every 2–4 weeks, to attain serum phosphorus levels within age-appropriate target ranges.
A total of 35 patients failed to complete the study, mainly due to renal transplantation. Among the remaining 66 patients, sevelamer carbonate significantly reduced mean serum phosphorus compared with placebo from a baseline value of 7.16 mg/dL, Dr Warady and his colleagues reported online ahead of print in Pediatric Nephrology. SC decreased serum phosphorus levels by a mean 0.90 and 1.18 mg/dL during the fixed-dose and dose-titration periods, respectively, compared with placebo. Mean serum phosphorus levels decreased by 1.23 mg/dL for patients receiving sevelamer continuously and by 1.13 for the group crossing over from placebo.
SC, which was developed as an alternative to sevelamer hydrochloride, appeared safe. Adverse events occurred in 39.2% and 38.8% of patients taking placebo or SC, respectively, during the fixed-dose period. During the dose-titration period, 82.4% of crossover patients and 71.4% of continuous SC patients experienced an adverse event (AE). Most AEs were gastrointestinal and mild to moderate in severity. Serious AEs, mainly viral or bacterial infections, occurred in 27.5% and 34.7% of crossover patients and continuous drug patients, respectively, over 6 months. The team found no adverse changes in serum lipids or vital signs.
“This study demonstrates that SC is an effective and well-tolerated drug for the treatment of hyperphosphatemia in pediatric patients with CKD,” Dr Warady and colleagues concluded. “The significant reduction in serum phosphorus levels in patients receiving SC versus placebo supports the pediatric indication for the drug.” Since the study mostly included adolescents, these conclusions do not necessarily apply to younger patients, the researchers noted.
The study was funded by Sanofi, the makers of sevelamer carbonate (Renvela).
Fathallah-Shaykh S, Drozdz D, Flynn J, et al. Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease. Pediatr Nephrol. doi: 10.1007/s00467-017-3787-0