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Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant

Published:March 09, 2023DOI:https://doi.org/10.1016/j.clinthera.2023.02.006
Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant
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      ABSTRACT

      Purpose

      Bezlotoxumab is approved for prevention of recurrent Clostridioides (Clostridium) difficile infection (CDI) in adults receiving antibacterial treatment for CDI who are at high risk for recurrent CDI. Previous studies have shown that although serum albumin levels are an important predictor for bezlotoxumab exposure, this has no clinically meaningful impact on efficacy. This pharmacokinetic modeling study assessed whether hematopoietic stem cell transplant (HSCT) recipients, at increased risk of CDI and exhibiting decreased albumin levels within the first month posttransplant, are at risk of clinically relevant reductions in bezlotoxumab exposure.

      Methods

      Observed bezlotoxumab concentration-time data pooled from participants in Phase III trials MODIFY I and II (ClinicalTrials.gov identifiers NCT01241552/NCT01513239) and three Phase I studies (PN004, PN005, and PN006) were used to predict bezlotoxumab exposures in two adult post-HSCT populations: A Phase Ib study of posaconazole including allogeneic HSCT recipients (ClinicalTrials.gov identifier NCT01777763; posaconazole-HSCT population); and a Phase III study of fidaxomicin for CDI prophylaxis (ClinicalTrials.gov identifier NCT01691248; fidaxomicin-HSCT population). The bezlotoxumab PK model used the minimum albumin level for each individual in post-HSCT populations to mimic a “worst-case scenario.”

      Findings

      Predicted worst-case bezlotoxumab exposures for the posaconazole-HSCT population (N = 87) were decreased by 10.8% versus bezlotoxumab exposures observed in the pooled Phase III/Phase I data set (N = 1587). No further decrease was predicted for the fidaxomicin-HSCT population (N = 350).

      Implications

      Based on published population pharmacokinetic data, the predicted decrease in bezlotoxumab exposure in the post-HSCT populations is not expected to have a clinically meaningful effect on bezlotoxumab efficacy at the recommended 10 mg/kg dose. Dose modification is therefore not required in the hypoalbuminemia setting expected post-HSCT. (Clin Ther. 2023;45:XXX–XXX) © 2023 Elsevier HS Journals, Inc.

      Keywords

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      Article info

      Publication history

      Published online: March 09, 2023
      Accepted: February 14, 2023

      Publication stage

      In Press Corrected Proof

      Identification

      DOI: https://doi.org/10.1016/j.clinthera.2023.02.006

      Copyright

      © 2023 Elsevier Inc.

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