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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPediatric Nephrology
DOIs
StateAccepted/In press - Sep 12 2017

Fingerprint

Chronic Renal Insufficiency
Phosphorus
Pediatrics
Safety
Placebos
Serum
Dialysis
Dietary Phosphorus
Hyperphosphatemia
Time and Motion Studies
Body Surface Area
United States Food and Drug Administration
Therapeutics
Least-Squares Analysis
Powders
Tablets
Multicenter Studies
Sevelamer
Arm
Phosphates

Keywords

  • Chronic kidney disease
  • Hyperphosphatemia
  • Pediatric patients
  • Phosphate binder
  • Sevelamer carbonate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Fathallah-Shaykh, S., Drozdz, D., Flynn, J., Jenkins, R., Wesseling-Perry, K., Swartz, S. J., ... Warady, B. A. (Accepted/In press). Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease. Pediatric Nephrology, 1-9. https://doi.org/10.1007/s00467-017-3787-0

Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease. / Fathallah-Shaykh, Sahar; Drozdz, Dorota; Flynn, Joseph; Jenkins, Randall; Wesseling-Perry, Katherine; Swartz, Sarah J.; Wong, Craig; Accomando, Beverly; Cox, Gerald F.; Warady, Bradley A.

In: Pediatric Nephrology, 12.09.2017, p. 1-9.

Research output: Contribution to journalArticle

Fathallah-Shaykh, S, Drozdz, D, Flynn, J, Jenkins, R, Wesseling-Perry, K, Swartz, SJ, Wong, C, Accomando, B, Cox, GF & Warady, BA 2017, 'Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease', Pediatric Nephrology, pp. 1-9. https://doi.org/10.1007/s00467-017-3787-0
Fathallah-Shaykh, Sahar ; Drozdz, Dorota ; Flynn, Joseph ; Jenkins, Randall ; Wesseling-Perry, Katherine ; Swartz, Sarah J. ; Wong, Craig ; Accomando, Beverly ; Cox, Gerald F. ; Warady, Bradley A. / Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease. In: Pediatric Nephrology. 2017 ; pp. 1-9.
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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.",
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AU - Wesseling-Perry, Katherine

AU - Swartz, Sarah J.

AU - Wong, Craig

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AU - Cox, Gerald F.

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N2 - 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.

AB - 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.

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