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Abstract: FR-PO496

Polymer Characterization of VS-505, a Novel Non-Absorbed, Calcium- and Aluminum-Free Phosphate Binder

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Wu-Wong, J. Ruth, Vidasym, Chicago, Illinois, United States
  • Chen, Yung-wu, Vidasym, Chicago, Illinois, United States
  • Zhang, Tony, Alebund, Shanghai, China
  • Tian, Jin, Alebund, Shanghai, China
Background

Inadequate control of phosphate in chronic kidney disease can lead to pathologies of clinical importance. VS-505 is a novel phosphate binder, which has been evaluated in hemodialysis subjects with hyperphosphatemia for 8 weeks (ClinicalTrials.gov Identifier #: NCT02469467) with the following results: (1) significantly reduced plasma phosphorus (Pi) in the treatment group (median Pi change -2.40 mg/dl), (2) no changes of iron parameters, and (3) no change of Ca levels, but a significant reduction in iPTH and CaxPi over the treatment period.

Methods

In this study, VS-505 was characterized by FT/IR spectroscopy (Fourier Transform Infrared), XPS (X-ray Photoelectron Spectroscopy), and 57Fe Mössbauer spectroscopy. VS-505 is not soluble in regular NMR solution/solvent, and thus was analyzed by a 750 MHz solid-state NMR spectroscopy. In 5% EDTA, VS-505 was partially solubilized, and the solubilized material was analyzed by size exclusion chromatograph.

Results

VS-505 has a high density (1.95 vs. 1.27 g/cm3 for sevelamer, by helium pycnometer) with a reduced pill size. When exposed to simulated gastric fluid, VS-505 exhibits a low swell volume (0.4 vs. 4 cm3/ml/0.1 g for sevelamer), and low iron release (<3% Fe+3 vs. 53% for sucroferric oxyhydroxide) after 2 hr of incubation at 37°C. FTIR spectrum of VS-505 conforms with that of gum Arabic, indicating that gum Arabic is the main component in VS-505. Results from XPS show the presence of Fe, C and O in VS-505, devoid of chloride and other impurities. Mössbauer spectroscopy results indicate that all Fe atoms in VS-505 are in the high-spin Fe+3 state. Solid-state NMR results show significant differences in chemical shifts between gum Arabic and VS-505, implicating the presence of tight complex between iron ion and gum Arabic. Results from the size exclusion chromatograph with solubilized material in 5% EDTA indicate that gum Arabic in VS-505 maintains its original molecular weight with chelated iron ion.

Conclusion

The characterization shows that VS-505 is a stable complex with 30% iron ion chelated to 70% gum Arabic (by weight). While effectively binding phosphate, VS-505 releases <3% of its iron content in gastric fluid, and doesn’t significantly affect blood iron parameters in both pre-clinical and clinical studies.