PII-078 - PHARMACOKINETIC BRIDGING OF JNJ-77242113 ORAL SOLUTION AND TABLET FORMULATIONS.

B. Tammara¹, T. Baguet², B. Knight³, A. Vermuelen², J. Odeja⁴, G. Liu¹, J. Badamo⁵, T. Kosoglou⁶, C. Deklotz¹; ¹Johnson and Johnson, PA, USA, ²Johnson and Johnson, Beerse, Belgium, ³Johnson & Johnson Innovative Medicine, San Diego, CA, USA, ⁴Johnson and Johnson, Cambridge, USA, ⁵Johnson and Johnson, Desmoulins, France, ⁶None, NJ, USA.

Background: JNJ-77242113 is a targeted oral peptide that potently inhibits the IL-23 receptor and is being developed for the treatment of inflammatory diseases. The objective was to compare the pharmacokinetics and bioavailability of the liquid and solid formulations used across development phase.

Methods: Part one of an open label, single dose, randomized crossover study (Study 77242113PSO1003) was conducted in 14 healthy participants to evaluate the bioavailability and pharmacokinetics (PK) of the 100 mg tablet formulation relative to a 100 mg dose of solution used in the first in human study. The relative oral bioavailability of a 200 mg JNJ 77242113 Phase 3 tablet formulation with respect to the 100 mg Phase 2 tablet formulation was evaluated in Study 77242113PSO1006, which was as a single dose, open-label, randomized, cross-over study in 24 healthy participants. Plasma samples were analyzed to determine the concentrations of JNJ-77242113 using a validated, specific, and sensitive LC-MS/MS. Pharmacokinetic parameters were calculated via noncompartmental analysis using Phoenix™ WinNonlin® 8.3.

Results: The mean PK parameters were comparable between the Phase 2 tablet and the oral solution. The geometric mean ratios (GMRs) of JNJ-77242113 Cmax, AUClast, and AUC∞ for the oral tablet versus the oral solution ranged from 105.59% to 109.68%. Statistical analysis from Study 77242113PSO1006 showed that the relative bioavailability of the Phase 3 200 mg tablet formulation was approximately 88%, 94%, and 95% for Cmax, AUClast, and AUC∞, respectively, when compared with the Phase 2 2x100 mg tablet formulation. Of note, the 90% CIs for the AUCs were contained within the classical bioequivalence criteria of 80.00% to 125.00%, while the lower limit of the 90% CI for Cmax was less than 80.00%. Mean JNJ 77242113 t1/2 was comparable for both study interventions, with values of 13.0 hours for the Phase 3 and 12.4 hours for the Phase 2 formulations.

Conclusion: The 200 mg Phase 3 tablet formulation performs similar to the 2x100 mg Phase 2 tablet formulation under fasted condition, which also showed similar bioavailability to the 100 mg dose of Phase 1 solution, thus establishing PK bridging between the different phases of clinical development for JNJ-77242113. No safety concerns were reported during the trial’s conduction.