Phase 4 Gastrointestinal Tolerability Study of Dimethyl Fumarate in Patients With Relapsing Forms of Multiple Sclerosis in the United States

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effect of symptomatic therapies on gastrointestinal (GI)-related events reported by participants with relapsing forms of multiple sclerosis (MS) initiating therapy with dimethyl fumarate (DMF) in the clinical practice setting. The secondary objectives of this study are as follows: To evaluate GI-related events requiring symptomatic therapy and the role of those therapies over time in participants with relapsing forms of MS initiating therapy with DMF in the clinical practice setting. To evaluate GI-related events that lead to DMF discontinuation after the use of symptomatic therapy in participants with relapsing forms of MS initiating therapy with DMF in the clinical practice setting.

Official Title
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A Multicenter, Open-Label, Single-Arm Study of Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera™ (Dimethyl Fumarate) Delayed-release Capsules

Conditions
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Relapsing Forms of Multiple Sclerosis

Intervention / Treatment
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* Drug: BG00012 (DMF)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Decision to treat with DMF must precede enrollment. Naïve to DMF or fumaric acid esters. Resides in the US and has a confirmed diagnosis of a relapsing form of MS. Satisfies the approved therapeutic indication(s) for DMF. Key Exclusion Criteria: Inability to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation. History of significant GI disease, chronic use of GI symptomatic therapy, active malignancies. Is participating in any other interventional clinical trial. NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimethyl Fumarate<br>120 mg DMF twice daily (BID) for the first 7 days and 240 mg DMF BID thereafter for 12 weeks of treatment. Participants will be instructed to take the DMF dose with food (with a meal or within 1 hour after a meal). | Drug: BG00012 (DMF)<br> <br> * Other names: dimethyl fumarate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS) | Severity of GI-related events in DMF-treated participants using the MOGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. | 12 Weeks | 
| Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale | Severity of GI-related events in DMF-treated participants using the MAGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. | 12 Weeks | 
| Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy | Percentage of participants reporting GI symptoms on the MOGISS, by those who utilized symptomatic therapy. | 12 Weeks | 
| Duration of GI-related Episodes in DMF-treated Participants | In participants who took symptomatic therapy, the median duration of acute GI episodes (in hours) was summarized for the overall treatment period, by symptom (nausea, diarrhea, lower abdominal pain, upper abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence). Table only includes the symptom duration for those symptoms with start and stop times entered in the eDiary (evaluable GI episodes), based on the MAGISS. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy | Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS. | 12 Weeks | 
| Participants' Use of Symptomatic Therapy, by Type and Category | The symptomatic therapies used by DMF-treated participants were self-reported by type and category. Each participant may have taken more than one symptomatic therapy type but was counted only once within each therapy category. Acetylsalicylic acid (ASA) is abbreviated in the table. | 12 Weeks | 
| Summary of Use and Days on Symptomatic Therapy, by Category | The total duration (in days) of use of each symptomatic therapy by participants as a result of GI symptoms experienced by DMF-treated participants is presented. If a participant had multiple different therapies on the same day, the days on symptomatic therapy was calculated as 1 day in the 'All Therapies' category. | 12 Weeks | 
| Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | The last symptomatic therapy prior to last dose of study medication was used to summarize the number of participants who discontinued DMF due to GI-related events. Participants may have taken more than one symptomatic therapy but are counted only once in the 'All Therapies' category. | 12 Weeks |