Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients.

Abstract

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.

• Authors: Stuart M Sprague, Adrian C Covic, Jürgen Floege, Markus Ketteler, Jaco Botha, Edward M Chong, Anjay Rastogi
• Journal: American journal of nephrology (Am J Nephrol) Vol. 44 Issue 2 Pg. 104-12 ( 2016) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 27434393 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 S. Karger AG, Basel.

Chemical References

• Biomarkers, Pharmacological
• Bone Density Conservation Agents
• Chelating Agents
• Drug Combinations
• Ergocalciferols
• Ferric Compounds
• Parathyroid Hormone
• Receptors, Calcitriol
• VDR protein, human
• sucroferric oxyhydroxide
• Sucrose
• paricalcitol
• Sevelamer

Topics

• Administration, Intravenous
• Administration, Oral
• Adult
• Aged
• Biomarkers, Pharmacological (blood)
• Bone Density Conservation Agents (administration & dosage, therapeutic use)
• Chelating Agents (pharmacology)
• Drug Combinations
• Drug Interactions
• Ergocalciferols (administration & dosage, therapeutic use)
• Female
• Ferric Compounds (pharmacology)
• Humans
• Hyperparathyroidism, Secondary (blood, drug therapy)
• Hyperphosphatemia (drug therapy)
• Male
• Middle Aged
• Parathyroid Hormone (blood, metabolism)
• Receptors, Calcitriol (agonists)
• Renal Dialysis (adverse effects)
• Renal Insufficiency, Chronic (blood, complications, therapy)
• Sevelamer (pharmacology)
• Sucrose (pharmacology)