Liquid Compared to Solid Oral Formulations of the Thyroid Hormone Receptor Agonist Elunetirom Under Fasted and Fed Conditions in Healthy Participants

Elunetirom (ABX-002) is a brain-targeted, oral prodrug being developed for the adjunctive treatment of major depressive disorder and bipolar depression. The active moiety, LL-340001, is a thyroid hormone receptor agonist with modest selectivity for beta over alpha thyroid hormone receptors. Upon entering the brain, the intended site of action, elunetirom is hydrolyzed by fatty acid amide hydrolase to LL-340001. In this 3-way randomized, crossover, bioequivalence study, the pharmacokinetics (PK) and safety of an oral liquid formulation used in early clinical development were compared with those of an oral solid formulation intended for later-stage development and potential commercialization, under fasted and fed conditions. Healthy adult participants received single doses of elunetirom (45 μg) as a liquid formulation under fasted conditions and as a solid formulation under fasted conditions and 30 min after consumption of a high-fat meal. Administration of the solid formulation under fasted conditions resulted in elunetirom and LL-340001 exposures similar to those observed with the liquid formulation and is therefore considered to have comparative bioavailability. Food intake increased elunetirom total exposure (AUC) compared with the fasted state but did not affect maximum exposure (Cmax). In contrast, administration with food reduced LL-340001 Cmax compared with the fasted state but did not affect AUC. Food intake delayed the time to reach Cmax (Tmax) for both elunetirom and LL-340001. Elunetirom, administered orally as a liquid and as a solid formulation, was safe and well tolerated under fed and fasted conditions.