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Abstract: TH-PO859

Novel Phosphate Binder Lanthanum Dioxycarbonate Does Not Demonstrate Clastogenic or Mutagenic Potential

Session Information

Category: CKD (Non-Dialysis)

  • 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Gupta, Pramod, Unicycive Therapeutics, Inc, Los Altos, California, United States
  • Khare, Atul, Unicycive Therapeutics, Inc, Los Altos, California, United States
Background

Lanthanum dioxycarbonate, RENAZORB (LDC), is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity vs. other P binders, with a potentially smaller pill size that is swallowed with water rather than chewed. We present studies assessing the clastogenic and mutagenic potential of LDC.

Methods

The clastogenic and mutagenic potential of LDC was tested using chromosome aberration assays and bacterial reverse mutation assays, respectively. For the chromosome aberration assays, Chinese hamster ovary cells were harvested 20 hours after treatment initiation. Cell growth and mitotic inhibition relative to control were evaluated. Statistical analysis was performed using the Fisher's Exact test.

Bacterial reverse mutation assays (Ames Test) consisted of two phases (initial toxicity mutation and confirmatory mutagenicity) and used Salmonella typhimurium and Escherichia coli tester strains with and without Aroclor-induced rat liver S9. Dose levels tested were 1.5, 5.0, 15, 50, 150, 500, 1500, and 5000 μg for the first phase and 50, 150, 500, 1500, and 5000 μg for the second phase.

Results

In the non-activated 4-hour exposure group, there was no increase in the proportion of cells with structural or numerical aberrations relative to control at any dose level (p>0.05). In the non-activated 20-hour exposure group, increases in the proportion of cells with numerical aberrations were not significant at any dose level (p>0.05).

In the initial toxicity-mutation assay, precipitate was observed beginning at 500 μg per plate, and no background lawn toxicity was observed. No positive mutagenic responses were observed with any of the tester strains with or without S9 activation. In the confirmatory mutagenicity assay, no appreciable toxicity or positive mutagenic responses were observed.

Conclusion

Lanthanum dioxycarbonate did not induce structural and numerical chromosome aberrations. LDC was negative in bacterial reverse mutation assay. These data support that LDC is safe and should be tested in the target population of patients with ESKD on dialysis with hyperphosphatemia. If approved, LDC would offer a small, swallowable phosphate binder option that could improve patient quality of life and potentially adherence.