Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease

  • Sahar Fathallah-Shaykh
  • Dorota Drozdz
  • Joseph Flynn
  • Randall Jenkins
  • Katherine Wesseling-Perry
  • Sarah J. Swartz
  • Craig Wong
  • Beverly Accomando
  • Gerald F. Cox
  • Bradley A. Warady
Original Article

Abstract

Background

Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study.

Methods

This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD. Following a 2–4 week screening phase, pediatric patients with a serum phosphorus level higher than age-appropriate levels were randomized to receive either SC or placebo as powder/tablets in 0.4–1.6 g doses, based on body surface area. The primary efficacy outcome was the change in serum phosphorus from baseline to end of the FDP in the SC versus placebo arms (analysis of covariance). The secondary outcome was mean change in serum phosphorus from baseline to end of DTP by treatment group and overall. Treatment-emergent/serious adverse events (AEs) were recorded.

Results

Of 101 enrolled patients (29 centers), 66 completed the study. The majority of patients were adolescents (74%; mean age 14.1 years) and on dialysis (77%). Renal transplant was the main reason for discontinuation. SC significantly reduced serum phosphorus from baseline levels (7.16 mg/dL) during the FDP compared to placebo (least square mean difference − 0.90 mg/dL, p = 0.001) and during the DTP (− 1.18 mg/dL, p < 0.0001). The safety and tolerability of SC and placebo were similar during the FDP, with patients in both groups reporting mild/moderate gastrointestinal AEs during the DTP.

Conclusions

Sevelamer carbonate significantly lowered serum phosphorus levels in hyperphosphatemic children with CKD, with no serious safety concerns identified.

Keywords

Chronic kidney disease Hyperphosphatemia Pediatric patients Sevelamer carbonate Phosphate binder 

Supplementary material

467_2017_3787_MOESM1_ESM.docx (12 kb)
Table S1(DOCX 11 kb)
467_2017_3787_Fig4_ESM.gif (66 kb)
Fig. S1

Subgroup analyses on changes in serum phosphorus levels from baseline during the fixed dose period—full Analysis Set (GIF 66.3 kb)

467_2017_3787_MOESM2_ESM.eps (1.5 mb)
High Resolution (EPS 1512 kb)

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Copyright information

© IPNA 2017

Authors and Affiliations

  • Sahar Fathallah-Shaykh
    • 1
  • Dorota Drozdz
    • 2
  • Joseph Flynn
    • 3
  • Randall Jenkins
    • 4
  • Katherine Wesseling-Perry
    • 5
  • Sarah J. Swartz
    • 6
  • Craig Wong
    • 7
  • Beverly Accomando
    • 8
  • Gerald F. Cox
    • 8
    • 9
  • Bradley A. Warady
    • 10
  1. 1.University of Alabama at BirminghamBirminghamUSA
  2. 2.Jagiellonian University Medical CollegeKrakowPoland
  3. 3.Seattle Children’s HospitalSeattleUSA
  4. 4.Oregon Health and Science UniversityPortlandUSA
  5. 5.University of CaliforniaLos AngelesUSA
  6. 6.Texas Children’s HospitalBaylor College of MedicineHoustonUSA
  7. 7.University of New Mexico Health Sciences CenterAlbuquerqueUSA
  8. 8.SanofiCambridgeUSA
  9. 9.Editas MedicineCambridgeUSA
  10. 10.Children’s Mercy Kansas CityKansas CityUSA

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