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Abstract: FR-PO130

Thrice Weekly vs. Daily Cinacalcet: Virtual Clinical Trial and Its Subsequent Clinical Validation in a Large US Hemodialysis Population

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Schappacher-Tilp, Gudrun, University of Graz, Graz, Austria
  • Hymes, Jeffrey L., Fresenius Medical Care North America, Franklin, Tennessee, United States
  • Fuertinger, Doris H., Fresenius Medical Care, Bad Homburg, Germany
  • Stennett, Amanda, Fresenius Medical Care, Bad Homburg, Germany
  • Kotanko, Peter, Renal Research Institute, New York, New York, United States
Background

Secondary hyperparathyroidism affects most hemodialysis (HD) patients. Current therapies include cinacalcet. Its label indicates a daily, oral administration with food. However, high pill burden and gastrointestinal side effects limit patient adherence. The aim of this study was to explore in a virtual clinical trial (VCT) whether directly observed 3x weekly in-center (IC) administration is sufficient to control parathyroid hormone (PTH) levels. The VCT findings were compared to observations in a subsequent roll-out of 3x weekly IC cinacalcet in a large U.S. HD population.

Methods

We utilized 2 mathematical models, a cinacalcet pharmacokinetic model (Schappacher-Tilp, Cell Phys Biochem 2019) and a comprehensive model of parathyroid gland biology (Schappacher-Tilp, Phys Rep 2019). We simulated 2 populations, cinacalcet naïve patients and patients on cinacalcet for ≥ 12 weeks. We then compared PTH levels attained with directly observed 3x weekly vs. daily administration; for the latter we considered a real-life adherence rate of 64%, based on pharmacy data. A subsequent clinical roll-out involved 4865 HD patients on daily cinacalcet for ≥ 12 weeks who were subsequently switched to 3x weekly IC cinacalcet for ≥ 12 weeks.

Results

Our VCT showed that patient adherence significantly impacts PTH levels. The PTH lowering effects of prescribed daily cinacalcet administration with limited patient adherence were almost identical to directly observed 3x weekly IC administration. Model predictions were corroborated by subsequent clinical observations (Fig 1).

Conclusion

Directly observed 3x weekly IC administration of cinacalcet is not inferior to daily administration with realistic adherence rates. Our results support the utility of VCTs for exploring alternative therapy regimens.