BG-12 (Dimethyl Fumarate) with Aspirin Pretreatment or Slow Dose Titration

Background: BG-12 (dimethyl fumarate) is under evaluation as an oral treatment for relapsing MS, with significant benefits and an acceptable safety profile demonstrated in Phase 3 studies. Common adverse events associated with BG-12 included flushing and gastrointestinal (GI) events. For most patients these events were mild/moderate in severity and decreased substantially in incidence after the first month of treatment.

Objectives: To evaluate the effects of aspirin pretreatment or slow dose titration on flushing and GI events associated with BG-12 in an 8-week, randomized, double-blind, Phase 3b study in healthy volunteers.

Methods: Subjects were randomized equally to four groups. All groups received study treatment (placebo or BG-12) twice daily (BID) and aspirin or placebo prior to study treatment. Groups 1 and 3 received BG-12 120 mg BID for 1 week then 240 mg BID for 7 weeks. In Weeks 1–4, Group 3 also received BID aspirin pretreatment 30 minutes before each BG-12 dose, while the other groups received matching placebo pretreatment. Group 2 received placebo BID for 8 weeks. Group 4 received BG-12 slow titration: 120 mg once daily, 120 mg BID, and 240 mg in the morning/120 mg at night (360 mg/day) in Weeks 1, 2 and 3, respectively, then 240 mg BID in Weeks 4–8. Flushing and GI events were rated in an eDiary using four subject-reported tolerability scales.

Results: A total of 172 subjects were dosed and 141 completed the 8-week study. Incidence and severity of flushing and GI events will be summarized for each treatment group, and the impact of aspirin pretreatment and slow titration on flushing and GI events associated with BG-12 will be assessed.

Conclusions: The profile of flushing and GI events in this volunteer study is anticipated to be consistent with previous findings in patients with MS treated with BG-12. The results will demonstrate whether aspirin pretreatment or slow dose titration can reduce the incidence and intensity of flushing and/or GI events onset with BG-12 treatment. These investigations will provide valuable insight into appropriate approaches for managing flushing and GI tolerability events that may occur at the onset of treatment with BG-12, thereby supporting the potential for continued therapy and optimal outcomes.