Abstract Details

Title Favorable Metabolism and Pharmacokinetics of Formulations of XP23829, a Novel Fumaric Acid Ester, in Healthy Subjects

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 189

Objective

Background BACKGROUND: Fumaric acid ester compounds have shown immuno-modulatory and neuroprotective effects in cell-based systems and preclinical models of Multiple Sclerosis (MS). Dimethyl fumarate (DMF), a fumaric acid ester prodrug of monomethyl fumarate (MMF), was effective in clinical trials of MS. XP23829 is a novel prodrug of MMF that had similar efficacy to DMF in a mouse model of MS but caused less stomach irritation than DMF in rats and monkeys.

Design/Methods DESIGN/METHODS: This randomized, double-blind, crossover food effect study of the pharmacokinetics, safety and tolerability of XP23829 formulations enrolled 60 healthy adult subjects into five cohorts (12 subjects per cohort). Each cohort received single oral doses of one of four XP23829 formulations (107 mg eq of MMF) or placebo in both fed and fasted states.

Results RESULTS: For all XP23829 formulations, MMF was observed in blood; intact prodrug and potential desmethyl metabolite were not detected. Formulation 1 produced mean (SD) maximum MMF concentrations (Cmax) of 529 (233) ng/mL fasted and 366 (320) ng/mL fed. MMF AUC was 762 (248) ng*h/mL fasted and 807 (445) ng*h/mL fed. In contrast, MMF release from Formulation 2 was more sustained and minimally affected by food: Cmax 143 (61) ng/mL fasted and 217 (89) ng/mL fed; AUC 625 (216) ng*h/mL fasted and 750 (242) ng*h/mL fed. Promoiety was cleared from blood with a half life around three hours. XP23829 was generally well-tolerated during the trial. All subjects completed both dosing periods. All AEs were mild. AEs reported in more than one subject and more frequently for XP23829 than for placebo were flushing and feeling hot, observed primarily for Formulation 1.

Conclusions CONCLUSIONS: The trial demonstrated that administration of formulations of XP23829 provides a range of MMF exposure profiles in blood, and supports further evaluation for potential once-a-day and twice-a-day treatments.

Authors/Disclosures
Dmitri V. Lissin, MD (Scilex Holding) PRESENTER	Dr. Lissin has received personal compensation in the range of $500,000-$999,999 for serving as a Chief Medical Officer with Scilex Holding .
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Kenneth Cundy, PhD	No disclosure on file

��ɫ��

��ɫ��