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Abstract: SA-PO255

Drug-Drug Interaction Between Phosphate Binders and Daprodustat in ASCEND-D

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Stankus, Nicole S., University of Chicago, Chicago, Illinois, United States
  • Meadowcroft, Amy M., GSK, Collegeville, Pennsylvania, United States
  • Bhatt, Nisha, GSK, Collegeville, Pennsylvania, United States
  • Jones-Leone, Angela Renne, GSK, Collegeville, Pennsylvania, United States
  • Bhatt, Purav Rahulkumar, GSK, Collegeville, Pennsylvania, United States
  • Shannon, Jennifer, GSK, Collegeville, Pennsylvania, United States
  • Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
Background

Daprodustat (Dapro), a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI), is an oral alternative to erythropoiesis-stimulating agent (ESA) therapy and is indicated in the USA for the treatment of anemia of chronic kidney disease (CKD) in adults receiving dialysis for at least four months. Phosphate binders (PB) are widely prescribed for hemodialysis (HD) or peritoneal dialysis (PD) patients (pts) in the USA (66.1% and 57.8%, respectively). Previous studies indicate the absorption of some HIF-PHIs may be affected by co-administration with PBs.1,2 However, results from a phase II study of Dapro indicate PB use does not have a major impact on hemoglobin (Hb) values. Here we examined the effect of PB use at baseline on Dapro treatment dose and Hb using data from the phase III ASCEND-D study (NCT02879305) (Singh AK, et al. N Engl J Med. 2021;385:2325–2335).

Methods

In ASCEND-D, 2964 pts with CKD undergoing dialysis and receiving ESAs were randomized in a 1:1 ratio to receive Dapro or injectable ESAs (epoetin alfa in HD pts or darbepoetin alfa in PD pts). Change in Hb and median doses from Weeks 1 to 52 was reported by baseline PB use and dialysis modality.

Results

656 (22%) pts reported no PB use at baseline. In HD pts, the Hb profile in baseline PB users was generally indistinguishable from that in non-users, and the median Dapro/ESA dose was approximately one dose step higher than for pts with no PB use (Fig. A). While similar results were observed in PD pts, the number of pts reporting no PB use at baseline was too small to draw definitive conclusions (Fig. B). At Week 52, the majority of PB users and non-users had Hb within 10–11.5 g/dL, irrespective of treatment randomization.

Conclusion

This analysis demonstrated that baseline PB use had no major impact on the effect of Dapro on Hb levels in HD and PD pts.

Funding

  • Commercial Support – The study and this analysis were funded by GSK.