Endocrine Abstracts

JOINT318

Objectives: The primary objectives were to evaluate the relative bioavailability (BA) between the tablet and capsule formulations, to assess the food effect (FE) on the BA of the capsule formulation, and to evaluate the safety and tolerability of the capsule formulation. Secondary objectives included evaluating the PK of the major metabolite of LUM-201 (M8) and the PD response (serum GH) to the new formulation.

Methods: Part 1 was a 4-sequence, 4-treatment, 4-period crossover study to determine the relative bioavailability of the tablet and the new capsule formulation. Part 2 was a 2-sequence, 2-treatment, 2-period crossover study to evaluate the food effect on the capsule formulation. Comparisons are reported as Dose-Normalized AUC_0-inf (DNAUC_0-inf) and Dose-Normalized C_max (DNC_max).

Results: The new capsule formulation showed bioequivalence to the tablet formulation in terms of DNAUC_0-last and DNAUC_0-inf. Compared with the 90 mg tablet dose, significant decreases in DNC_max were observed with 85. 3mg whole capsule (14. 1% lower), with 85. 3mg capsule contents in a dosing cup (20. 4% lower), or 85. 3mg capsule contents in banana puree (14. 4% lower). Food increased the C_max of LUM-201 by 64. 4% and AUC_0-last and AUC_0-inf by 17. 8%. There was no significant effect of food on the PK parameters of the metabolite M8; the geometric least squares (GLS) mean ratio% (90% CI) for M8 C_max was 106. 30% (74. 20, 152. 20), and for AUC_0-last and AUC_0-inf, the ratios were 96. 40% (82. 40, 112. 80) and 96. 50% (82. 70, 112. 50), respectively. Serum GH concentrations increased similarly across all dose formulation treatment groups. Regarding food effect with LUM-201, the fed state reached C_max 30 min later than the fasted state (C_max of fed = 14. 10 ng/mL; C_max of fasted = 22. 18 ng/mL). Importantly, serum GH reached similar C_max values by 1. 5 h after dose regardless of fed state. Serum IGF-1 concentrations remained stable over time in both parts of the study. Safety and tolerability of LUM-201 were consistent with the established safety profile; no SAEs were reported.

Conclusions: Overall, the study demonstrated that the new capsule formulation of LUM-201 has a favorable investigational safety profile, is well-tolerated, and exhibits comparable bioavailability to the tablet formulation, with consistent PK parameters for the metabolite M8 and encouraging PD responses. The new LUM-201 capsule formulation filled with mini-tablets produces similar PK and PD results compared with the current tablet formulation and offers children & their caretakers a more flexible and user-friendly oral capsule formulation.