Relapsing Forms of Multiple Sclerosis
Conditions
Brief summary
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.
Interventions
DRUGBG00012 (DMF)
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of GI-related Episodes in DMF-treated Participants | 12 Weeks | 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. |
| Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS) | 12 Weeks | 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. |
| Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale | 12 Weeks | 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. |
| Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy | 12 Weeks | Percentage of participants reporting GI symptoms on the MOGISS, by those who utilized symptomatic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy | 12 Weeks | Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS. |
| Participants' Use of Symptomatic Therapy, by Type and Category | 12 Weeks | 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. |
| Summary of Use and Days on Symptomatic Therapy, by Category | 12 Weeks | 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. |
| Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | 12 Weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dimethyl Fumarate 120 mg dimethyl fumarate (DMF) twice daily (BID) for the first 7 days and 240 mg DMF BID thereafter for 12 weeks of treatment. Participants were instructed to take the DMF dose with food (with a meal or within 1 hour after a meal). | 233 |
| Total | 233 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 24 |
| Overall Study | Did Not Receive Any Study Drug | 4 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Dimethyl Fumarate |
|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 11.66 |
| Sex: Female, Male Female | 181 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 233 |
| serious Total, serious adverse events | 7 / 233 |
Outcome results
Primary
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.
Time frame: 12 Weeks
Population: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]); n=number of participants with evaluable GI symptom specified.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Nausea; n=88 | 2.0 hours | Full Range 1.81 |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Diarrhea; n=78 | 1.6 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Lower Abdominal Pain; n=67 | 2.0 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Upper Abdominal Pain; n=66 | 1.8 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Vomiting; n=27 | 0.4 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Indigestion; n=52 | 1.9 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Constipation; n=7 | 6.0 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Bloating; n=41 | 3.0 hours | — |
| Dimethyl Fumarate | Duration of GI-related Episodes in DMF-treated Participants | Flatulence; n=68 | 2.1 hours | — |
Primary
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.
Time frame: 12 Weeks
Population: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimethyl Fumarate | Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy | 54.1 percentage of participants |
Primary
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.
Time frame: 12 Weeks
Population: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dimethyl Fumarate | Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS) | 4.8 units on a scale | Standard Deviation 2.34 |
Primary
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.
Time frame: 12 Weeks
Population: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dimethyl Fumarate | Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale | 4.7 units on a scale | Standard Deviation 2.13 |
Secondary
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.
Time frame: 12 Weeks
Population: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | All therapies | 13 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Anti-acid production | 10 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Antacid | 6 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Antisecretory/antimicrobial | 6 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Anti-diarrheal (anti-peristaltic) | 5 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Anti-emetic (central) | 5 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Anti-emetic (prokinetic) | 2 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Laxative, fiber/probiotic | 1 participants |
| Dimethyl Fumarate | Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy | Laxative, prokinetic | 1 participants |
Secondary
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.
Time frame: 12 Weeks
Population: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Omeprazole | 18 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Antacid | 57 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Calcium carbonate | 50 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Magnesium (Mg) hydroxide | 4 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Aluminum (Al) hydroxide | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Al hydroxide, Mg hydroxide, simethicone | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: ASA, citric acid, sodium bicarbonate | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Generic anatacid | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Nauzene | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Sucralfate | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Antisecretory/antimicrobial | 49 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Bismuth subsalicylate | 49 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Anti-acid production | 43 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Ranitidine | 15 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Famotidine | 14 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Lansoprazole | 10 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Pantoprazole | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Cimetidine | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Anti-bloating/anti-constipation agent | 33 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Simethicone | 29 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Docusate | 5 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Alpha-galactosidase | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Enema | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Antidiarrheal (anti-peristaltic) | 32 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Loperamide | 29 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Diphenoxylate | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Dicyclomine | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Anti-emetic (central) | 18 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Ondansetron | 8 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Promethazine | 7 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Dimenhydrinate | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Tetrahydrocannabinol | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Laxative, fiber/probiotic | 10 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Generic laxative | 5 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Psyllium fiber | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Culturelle | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Laxative, hygroscopic/osmotic | 10 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Polyethylene glycol | 4 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Phosphorated carbohydrate solution | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Sennosides | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Osmotic | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Laxative, prokinetic | 7 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Bisacodyl | 7 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category:Analgesic (nonsteroidal antiinflammatory) | 5 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Ibuprofen | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Naproxen | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: ASA | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Anti-allergic | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Montelukast | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Diphenhydramine | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Anti-emetic (pro-kinetic) | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Metoclopramide | 3 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: Analgesic | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Acetaminophen | 2 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Category: No treatment type recorded | 1 participants |
| Dimethyl Fumarate | Participants' Use of Symptomatic Therapy, by Type and Category | Therapy: Not available | 1 participants |
Secondary
Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy
Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS.
Time frame: 12 Weeks
Population: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimethyl Fumarate | Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy | 54.1 percentage of participants |
Secondary
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.
Time frame: 12 Weeks
Population: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]). n= number of participants using the therapy specified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | All therapies; n=128 | 10.4 days | Standard Deviation 13.46 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Antacid; n=57 | 5.9 days | Standard Deviation 10.77 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Antisecretory/antimicrobial; n=49 | 6.3 days | Standard Deviation 12.34 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-acid production; n=43 | 9.0 days | Standard Deviation 11.16 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-bloating/anti-constipation agent; n=33 | 5.9 days | Standard Deviation 10.86 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-diarrheal (anti-peristaltic); n=32 | 3.9 days | Standard Deviation 3.88 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-emetic (central); n=18 | 2.9 days | Standard Deviation 2 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Laxative, fiber/probiotic; n=10 | 5.0 days | Standard Deviation 5.64 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Laxative, hygroscopic/osmotic; n=10 | 3.7 days | Standard Deviation 3.06 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Laxative, prokinetic; n=7 | 1.6 days | Standard Deviation 0.79 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Analgesic (nonsteroidal antiinflammatory); n=5 | 4.6 days | Standard Deviation 7.5 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-allergic; n=3 | 12.0 days | Standard Deviation 9.85 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Anti-emetic; n=3 | 9.7 days | Standard Deviation 12.42 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | Analgesic; n=2 | 4.5 days | Standard Deviation 4.95 |
| Dimethyl Fumarate | Summary of Use and Days on Symptomatic Therapy, by Category | No treatment type recorded; n=1 | 1.0 days | — |