title: Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients.
abstract: Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients.
  
  
  
  One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared.
  
  
  
  In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87).
  
  
  
  In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.
authors.affiliation: NorthShore University Health System, University of Chicago, Chicago, Ill., USA.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Sprague
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Covic
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.forename: Jaco
authors.initials: J
authors.lastname: Botha
authors.forename: Edward M
authors.initials: EM
authors.lastname: Chong
authors.forename: Anjay
authors.initials: A
authors.lastname: Rastogi
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000097:blood; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002614:Chelating Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D004872:Ergocalciferols / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D054559:Hyperphosphatemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000819:agonists*; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D000069603:Sevelamer / Q000494:pharmacology*; D013395:Sucrose / Q000494:pharmacology*
chemical_list: D054316:Biomarkers, Pharmacological; D050071:Bone Density Conservation Agents; D002614:Chelating Agents; D004338:Drug Combinations; D004872:Ergocalciferols; D005290:Ferric Compounds; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C000599459:sucroferric oxyhydroxide; D013395:Sucrose; C084656:paricalcitol; D000069603:Sevelamer