Bioequivalence of tegomil fumarate gastro-resistant capsules versus dimethyl fumarate gastro-resistant capsules under different fed conditions: two randomized, crossover, phase I studies.

OBJECTIVE

Tegomil fumarate is a newly approved treatment for relapsing-remitting multiple sclerosis. Two phase I studies were performed under different fed conditions to evaluate the bioequivalence and tolerability of tegomil fumarate versus dimethyl fumarate in healthy volunteers.

METHODS

These were single-center, open-label, randomized, crossover (full replicate design), phase I studies. In both studies, healthy individuals aged 18-55 years received a single dose of tegomil fumarate (348.4 mg gastro-resistant hard capsule; "test") or an equimolar dose of dimethyl fumarate based on monomethyl fumarate (MMF) release (240.0 mg gastro-resistant hard capsule; "reference"). Participants were randomized to one of two treatment sequences (test-reference-test-reference or reference-test-reference-test), with 7 days between each drug administration. Before each drug administration, participants in Study 1 consumed a low-fat, low-calorie meal ("low-fed"), while those in Study 2 consumed a high-fat, high-calorie meal ("fed"). Pharmacokinetic parameters for MMF (active metabolite in both drugs) and adverse events (AEs) were assessed.

RESULTS

In total, 70 participants were enrolled (Study 1, N = 40; Study 2, N = 30). In both studies, pharmacokinetic parameters for MMF were similar between drugs. Geometric least-squares mean test/reference ratios for Cmax, AUC0-t, and AUC0-inf (and associated 90% confidence intervals for each) all fell within the accepted range of 80.00-125.00%, thereby demonstrating the bioequivalence of tegomil fumarate versus dimethyl fumarate. Both drugs were well tolerated, with no unexpected or serious AEs reported.

CONCLUSION

These studies demonstrated the tolerability of tegomil fumarate in healthy volunteers. Pharmacokinetic analyses showed that a single dose of 348.4 mg tegomil fumarate released the same amount of MMF as an equimolar dose of 240 mg dimethyl fumarate under both low-fed (low-calorie, low-fat) and fed (high-calorie, high-fat) dietary conditions.

CLINICAL TRIAL REGISTRATION: Agenţia Medicamentului şi Dispozitivelor Medicale [AMDM]; https://amdm.gov.md/ro, MMF-BEFI-07-TFB/24 (Rg04-000227) (Study 1; registered September 4, 2024); MMF-BEFI-06-TFB/22 (Rg04-000165) (Study 2; registered July 10, 2023).