Frontiers in neurology · 2026
Bioequivalence of tegomil fumarate gastro-resistant capsules versus dimethyl fumarate gastro-resistant capsules under different fed conditions: two randomized, crossover, phase I studies.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Zietz Katja, Savu Simona Rizea, Remis Lina, Nicolau Natalia, Iordachescu Adriana, Herb Florian
Аннотация
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).
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).