Abstract: PO0293
Daprodustat Interaction with Phosphate Binders Has Minimal Impact on Hemoglobin Values in Hemodialysis Population
Session Information
- Anemia and Iron Management
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Cizman, Borut, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Meadowcroft, Amy M., GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Biswas, Nandita, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Sprys, Michael, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States
Background
Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (PHI) in phase 3 development for the treatment of anemia of chronic kidney disease. Phosphate binders (PB) are widely prescribed for patients on hemodialysis (HD) to control hyperphosphatemia. PB may interfere with medication absorption; thus, coadministration with a PHI may potentially impact the latter's efficacy on hemoglobin (Hgb). The purpose of this analysis was to determine whether administration of daprodustat in subjects receiving PB has an impact on Hgb values in the HD population.
Methods
The 24-week GSK PHI113633 study (NCT01977482) included 216 subjects on maintenance HD previously treated with recombinant human erythropoietin (Clin Kidney J 2019;12:139–148). Target Hgb range was 10.0 g/dL to 11.5 g/dL. Baseline PB users were defined as a prespecified study subgroup. The difference in mean Hgb values at Week 24 between treatment groups was summarized overall and by subgroup. Comparisons were performed for the Week 24 Hgb (post hoc), as well as the final dose of daprodustat, for those receiving/not receiving PB.
Results
The majority of HD subjects received PB at baseline; 136/177 (77%) of daprodustat and 33/39 (85%) of control subjects were taking PB, with comparable phosphate control at baseline (mean [±SD] phosphate: daprodustat 1.76 mmol/L [0.56]; control 1.67 mmol/L [0.44]]). All subjects receiving PB at baseline, except two, continued them throughout the study.
No meaningful difference in Hgb change from baseline (CFB) at Week 24 was noted between treatment groups. The final median dose for subjects on daprodustat was the same for those receiving and those not receiving PB (6 mg), with no meaningful difference in the Hgb at Week 24 (mean [±SD]: PB use=Yes 10.40 g/dL [0.95]; PB use=No 10.79 g/dL [0.95]).
Conclusion
These results suggest that PB use does not have a major impact on Hgb values during the 24-week study. Results of an ongoing, phase 3 dialysis study of daprodustat compared with conventional treatment are awaited to confirm these initial observations.
| Group | Mean (±SD) baseline Hgb (g/dL) for daprodustat vs control | Mean (95% CI) difference in CFB Hgb (g/dL) at Week 24 |
| Overall population | 10.39 (0.66) vs 10.55 (0.94) | -0.12 (-0.51, 0.27) |
| Baseline PB use = Yes | 10.38 (0.62) vs 10.48 (0.73) | -0.21 (-0.63, 0.21) |
| Baseline PB use = No | 10.43 (0.77) vs 10.94 (1.76) | 0.25 (-0.72, 1.23) |
Funding
- Commercial Support –