PMID- 28900759 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20190107 IS - 1432-198X (Electronic) IS - 0931-041X (Linking) VI - 33 IP - 2 DP - 2018 Feb TI - Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease. PG - 325-333 LID - 10.1007/s00467-017-3787-0 [doi] 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. FAU - Fathallah-Shaykh, Sahar AU - Fathallah-Shaykh S AD - University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Drozdz, Dorota AU - Drozdz D AD - Jagiellonian University Medical College, Krakow, Poland. FAU - Flynn, Joseph AU - Flynn J AD - Seattle Children's Hospital, Seattle, WA, USA. FAU - Jenkins, Randall AU - Jenkins R AD - Oregon Health and Science University, Portland, OR, USA. FAU - Wesseling-Perry, Katherine AU - Wesseling-Perry K AD - University of California, Los Angeles, CA, USA. FAU - Swartz, Sarah J AU - Swartz SJ AD - Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA. FAU - Wong, Craig AU - Wong C AD - University of New Mexico Health Sciences Center, Albuquerque, NM, USA. FAU - Accomando, Beverly AU - Accomando B AD - Sanofi, Cambridge, MA, USA. FAU - Cox, Gerald F AU - Cox GF AD - Sanofi, Cambridge, MA, USA. AD - Editas Medicine, Cambridge, MA, USA. FAU - Warady, Bradley A AU - Warady BA AD - Children's Mercy Kansas City, 2401 Gilham Road, Kansas City, MO, 64108, USA. bwarady@cmh.edu. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170912 PL - Germany TA - Pediatr Nephrol JT - Pediatric nephrology (Berlin, Germany) JID - 8708728 RN - 0 (Chelating Agents) RN - 9YCX42I8IU (Sevelamer) SB - IM MH - Adolescent MH - Chelating Agents/*therapeutic use MH - Child MH - Female MH - Humans MH - Hyperphosphatemia/*drug therapy/etiology MH - Male MH - Renal Insufficiency, Chronic/complications/*drug therapy MH - Sevelamer/*therapeutic use OTO - NOTNLM OT - Chronic kidney disease OT - Hyperphosphatemia OT - Pediatric patients OT - Phosphate binder OT - Sevelamer carbonate EDAT- 2017/09/14 06:00 MHDA- 2019/01/08 06:00 CRDT- 2017/09/14 06:00 PHST- 2017/04/11 00:00 [received] PHST- 2017/08/10 00:00 [accepted] PHST- 2017/08/08 00:00 [revised] PHST- 2017/09/14 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] PHST- 2017/09/14 06:00 [entrez] AID - 10.1007/s00467-017-3787-0 [pii] AID - 10.1007/s00467-017-3787-0 [doi] PST - ppublish SO - Pediatr Nephrol. 2018 Feb;33(2):325-333. doi: 10.1007/s00467-017-3787-0. Epub 2017 Sep 12.