LB-014 - POPULATION PHARMACOKINETIC ANALYSIS OF PHASE 1 SUBCUTANEOUS LEVOTHYROXINE FORMULATION (XP-8121).

D. Mould¹, R. Fitch², R. Huang², D. Harper²; ¹Projections Research, Inc, Phoenixville, PA, United States, ²Xeris Pharmaceuticals, Chicago, IL, United States.

Background: XP-8121 is a novel, subcutaneous (SC) injection formulation of levothyroxine that offers the potential to mitigate many of the dosing and absorption challenges associated with oral formulations. This analysis was conducted to develop a population pharmacokinetic (PPK) model to describe the concentration time profile of XP-8121 and use the model for simulations with different dosing scenarios.

Methods: Nonlinear, mixed-effect modeling (NONMEM) was used to analyze pharmacokinetic (PK) data. The final model was used to simulate 500 replicates using the design, dose regimen, and covariates of a Phase 1, randomized, open-label, crossover, bioavailability study of XP-8121 and oral levothyroxine (Synthroid®) in 60 healthy volunteers.

Results: XP-8121 is best described by a 1-compartment model with first-order elimination. Body weight (WT) was identified as a covariate on the clearance from central compartment (CL) and on central volume of distribution (Vc). XP-8121 (1200 µg SC) and Synthroid (300 µg PO) are similar in exposure at steady-state (AUC and Cmax) based on the simulations from the final PPK model (Figure).

Conclusion: The final PPK model provides adequate predictive performance for XP-8121 to inform future Phase 2 trials.