Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease

Abstract

Background: Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety.

Methods: This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results: Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%).

Conclusions: SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.

Keywords: Children; Chronic kidney disease; Hyperphosphatemia; Phosphate binder; Safety profile; Sucroferric oxyhydroxide.

Fig. 1

Study design. **Age-related sP targets for washout period 0 to < 6 months, > 8.1 mg/dL; ≥ 6 months to < 1 year, > 7.1 mg/dL; ≥ 1 year to < 6 years, > 6.3 mg/dL; ≥ 6 years to < 13 years, > 5.5 mg/dL; ≥ 13 years to < 18 years, > 4.2 mg/dL. ^†Age-related sP targets post-randomization 0 to 1 year, 5.0–7.8 mg/dL; ≥ 1 year to < 6 years, 4.5–6.5 mg/dL; ≥ 6 years to < 13 years, 3.6–5.8 mg/dL; ≥ 13 years to < 18 years, 2.3–4.5 mg/dL [27]. ^††All subjects (including withdrawn) followed for 14 days after the last study visit. PBs, phosphate binders; sP, serum phosphorus

Fig. 2

Patient disposition (stage 1 and stage 2). SFOH, sucroferric oxyhydroxide. Note: More than one reason for study withdrawal may have been given for an individual subject

Fig. 3

Mean change (± SEM) from baseline in serum phosphorus levels to end of stage 2 in the sucroferric oxyhydroxide group (FAS; N = 65). FAS, full analysis set; SEM, standard error of the mean. Data are from central laboratory