Neurology and therapy · 2025
A Randomised, Double-Blind Study Comparing the Gastrointestinal Tolerability of Tegomil Fumarate Versus Dimethyl Fumarate in Healthy Volunteers.
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Fonseca Marlene, Bauzà Valverde Gabriel, Bendarraz Abdelkarim, Catalán Flores Carmen, Sharma Vikas Mohan
Аннотация
INTRODUCTION: Widely used to treat multiple sclerosis, dimethyl fumarate (DMF) is a prodrug metabolized in vivo to monomethyl fumarate (MMF) and methanol; the latter is a gastrointestinal (GI) irritant. GI adverse events (AEs) commonly cause DMF discontinuation. Tegomil fumarate (TMF) comprises two MMF moieties joined by tetraethylene glycol, a low molecular polyethylene glycol (PEG). TMF is cleaved in vivo to MMF and the pharmacologically inactive PEG.
METHODS: This randomised, double-blind study compared the GI tolerability of TMF 348 mg and DMF 240 mg, administered twice daily, in healthy adults (3:1 female:male ratio) aged 18-55 years. Participants completed daily questionnaires in an electronic diary, including the Modified Overall Gastrointestinal Symptom Scale (MOGISS), Modified Acute Gastrointestinal Symptom Scale, Flushing Symptom Questionnaire and an ad hoc quality of life assessment. The primary endpoint was the area under the curve (AUC) for each individual MOGISS symptom over 5 weeks of treatment. Between-group treatment differences for each MOGISS symptom AUC were analysed using hierarchical testing in a predefined sequence starting with abdominal pain.
RESULTS: The study enrolled 210 participants; the full analysis set comprised 208 (155 females, 53 males). While AUC values were lower for TMF than DMF for most MOGISS symptoms, the between-group difference for abdominal pain was not statistically different (p = 0.0513) so all subsequent statistical analyses were considered exploratory. MOGISS total and composite score, the number of days with symptoms and number of symptoms were lower with TMF than DMF. Fewer participants receiving TMF (57.7%) versus DMF (73.6%) reported GI AEs or discontinued because of GI AEs (TMF n = 0, DMF n = 2).
CONCLUSIONS: The between-group difference for the AUC of MOGISS abdominal pain score was not statistically different. However, compared with DMF, TMF showed improved GI tolerability profile in terms of self-assessed GI events and GI AEs leading to discontinuation.
METHODS: This randomised, double-blind study compared the GI tolerability of TMF 348 mg and DMF 240 mg, administered twice daily, in healthy adults (3:1 female:male ratio) aged 18-55 years. Participants completed daily questionnaires in an electronic diary, including the Modified Overall Gastrointestinal Symptom Scale (MOGISS), Modified Acute Gastrointestinal Symptom Scale, Flushing Symptom Questionnaire and an ad hoc quality of life assessment. The primary endpoint was the area under the curve (AUC) for each individual MOGISS symptom over 5 weeks of treatment. Between-group treatment differences for each MOGISS symptom AUC were analysed using hierarchical testing in a predefined sequence starting with abdominal pain.
RESULTS: The study enrolled 210 participants; the full analysis set comprised 208 (155 females, 53 males). While AUC values were lower for TMF than DMF for most MOGISS symptoms, the between-group difference for abdominal pain was not statistically different (p = 0.0513) so all subsequent statistical analyses were considered exploratory. MOGISS total and composite score, the number of days with symptoms and number of symptoms were lower with TMF than DMF. Fewer participants receiving TMF (57.7%) versus DMF (73.6%) reported GI AEs or discontinued because of GI AEs (TMF n = 0, DMF n = 2).
CONCLUSIONS: The between-group difference for the AUC of MOGISS abdominal pain score was not statistically different. However, compared with DMF, TMF showed improved GI tolerability profile in terms of self-assessed GI events and GI AEs leading to discontinuation.