Liquid Compared to Solid Oral Formulations of the Thyroid Hormone Receptor Agonist Elunetirom Under Fasted and Fed Conditions in Healthy Participants.
4 affiliations
- 1Autobahn Therapeutics, San Diego, California, USA.
- 2Celerion, Lincoln, Nebraska, USA.
- 3CB Pharma Consulting Services LLC, Cambridge, Massachusetts, USA.
- 4Oregon Health & Science University, Portland, Oregon, USA.
Abstract
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.
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BibTeX
@article{harris2026liquid,
title = {{Liquid Compared to Solid Oral Formulations of the Thyroid Hormone Receptor Agonist Elunetirom Under Fasted and Fed Conditions in Healthy Participants.}},
author = {Jason R Harris and Aernout D van Haarst and Jill Baccei and Bridgette Franey and Jason Everett and Kory George and Sabina Paglialunga and Kenneth Webster and Michelle Hillstrand and Chris Banfield and Thomas S Scanlan and Gudarz Davar},
journal = {Clinical and translational science},
year = {2026},
month = oct,
doi = {10.1111/cts.70743},
url = {https://europepmc.org/article/MED/42951879},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Liquid Compared to Solid Oral Formulations of the Thyroid Hormone Receptor Agonist Elunetirom Under Fasted and Fed Conditions in Healthy Participants.
AU - Jason R Harris
AU - Aernout D van Haarst
AU - Jill Baccei
AU - Bridgette Franey
AU - Jason Everett
AU - Kory George
AU - Sabina Paglialunga
AU - Kenneth Webster
AU - Michelle Hillstrand
AU - Chris Banfield
AU - Thomas S Scanlan
AU - Gudarz Davar
PY - 2026
DA - 2026/10/28
JO - Clinical and translational science
DO - 10.1111/cts.70743
UR - https://europepmc.org/article/MED/42951879
AB - 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.
SN - 1752-8054
SN - 1752-8062
ER -