Effect of Bismuth Subsalicylate on Gastrointestinal Tolerability in Healthy Volunteers Receiving Delayed-Release Dimethyl Fumarate

Background: Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting MS (RRMS) in the 2-year, Phase 3 DEFINE and CONFIRM studies. Common adverse events associated with delayed-release DMF included flushing and gastrointestinal (GI)-related events.

Objectives: In an 8-week, randomized, multicenter, double-blind, placebo-controlled, Phase 1 study (PREVENT), we evaluated the effect of bismuth subsalicylate (Pepto-Bismol^®) on GI-related events in healthy volunteers receiving delayed-release DMF.

Methods: Subjects were randomized 1:1 to receive bismuth subsalicylate 524 mg or placebo 30 minutes prior to delayed-release DMF (weeks 1-4). Delayed-release DMF was dosed at 120 mg BID (week 1) and 240 mg BID (weeks 2-8). Subjects were instructed to take delayed-release DMF with or within approximately 60 minutes after a meal. Using an eDiary, subjects recorded information regarding GI-related events and flushing events on the Modified Overall GastroIntestinal Symptom Scale (MOGISS) and Modified Global Flushing Severity Score (MGFSS) once daily for the previous 24 hours, and entered GI and flushing side effects using the Modified Acute GastroIntestinal Symptom Scale (MAGISS) and Modified Flushing Severity Scale (MFSS) after each administration of study drug. The primary endpoint was the time to first GI-related event.

Results: PREVENT enrolled 175 subjects with a mean age of 37 years (range: 18–64). Approximately half (50.9%) were female and a majority (67.4%) were Caucasian. PREVENT is ongoing; results will be reported.

Conclusions: The PREVENT study will evaluate the effect of bismuth subsalicylate on GI-related events in healthy volunteers receiving delayed-release DMF.