Supplementary Material for: Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients
2016-07-20T11:57:21Z (GMT) by
Background: 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. Methods: 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. Results: 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). Conclusions:In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.