Journal of Bioequivalence & Bioavailability

Abstract

A Healthy Participant Study to Evaluate the Bioequivalence of Form H and Form II Tablets of the Smallpox Antiviral Brincidofovir

David M Cassie*, Vanja Komlenovic, James McCarty, Jing Tian and Kevin Yeo

Background: Brincidofovir (BCV) is approved in the US and Canada for the treatment of human smallpox disease in adults and children, including neonates. In long-term storage, the commercially available BCV morphic Form II is slowly converted to a hydrated morphic Form H, which is more stable under ambient conditions. The purpose of this study (NCT05935917) was to compare the Bioequivalence (BE) of the morphic Forms II and H.

Methods: This was a Phase 1, open-label, randomized, two-period crossover study completed in healthy adults randomized to receive either a single 100 mg BCV Form II or Form H tablet and followed for 14 days after each dose to assess Pharmacokinetics (PK) and safety. The primary PK endpoints for demonstration of BE were C_max , AUC_last , and AUC_inf of BCV in plasma. BE was declared if the 90% Confidence Interval (CI) for the true ratio of test to reference geometric means fell entirely within the range of 0.80 to 1.25 for these endpoints.

Results: Forty-four (44) healthy subjects were enrolled, received Form II and Form H treatments, and completed all study visits and safety assessments. For the primary endpoints AUC_inf, AUC_last , and C_max, the 90% CIs of the geometric mean ratios for C_max, AUC_inf and AUC_last for Form H and Form II fell within the predefined range, thereby demonstrating BE. No new safety signals were identified.

Conclusion: Natural conversion of BCV from Form II to Form H over the shelf life does not change the safety or PK profile of BCV in healthy participants.

Published Date: 2025-05-19; Received Date: 2025-04-16