Relapsing-Remitting Multiple Sclerosis
Conditions
Keywords
Gastrointestinal event
Brief summary
The primary objective of this study is to evaluate the effect of symptomatic therapies on gastrointestinal-related events reported by participants with relapsing-remitting multiple sclerosis initiating therapy with BG00012 (dimethyl fumarate, DMF) in the clinical practice setting. The secondary objectives of this study in this study population are as follows: to evaluate gastrointestinal-related events requiring symptomatic therapy and the role of those therapies over time; to evaluate gastrointestinal-related events that lead to a physician's decision to manage the events with BG00012 dose modification; and to evaluate gastrointestinal-related events that lead to BG00012 discontinuation after the use of symptomatic therapy.
Interventions
DRUGdimethyl fumarate
capsules administered according to the prevailing product label
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: * Have a confirmed diagnosis of relapsing-remitting multiple sclerosis according to the current McDonald Criteria and satisfy the therapeutic indication as described in the official local registration for Tecfidera (dimethyl fumarate) * Naïve to dimethyl fumarate and fumaric acid esters Key
Exclusion criteria
* Female subjects who are currently pregnant or breastfeeding or who are considering becoming pregnant while in the study * History of significant gastrointestinal disease (e.g., irritable bowel disease, peptic ulcer disease, history of major gastrointestinal surgeries), or chronic use of gastrointestinal-related symptomatic therapy as determined by the Investigator (or ≥ 7 consecutive days of gastrointestinal-related symptomatic therapy * Known active malignancies * History of anaphylaxis or severe allergic reactions or known drug hypersensitivity * Current use of B vitamin supplements * In the opinion of the Investigator, blood test values suggestive of a low lymphocyte count or renal or hepatic impairment, as described in the product label precautions for use NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Up to Week 12 | Percentage of days with GI events as reported on MAGISS was calculated for each participant and each analysis period using the following formula: 100 x (# of days with \[GI\] events / # of days tolerability scale completed). The ST categories were provided by Biogen Medical team as follows: ST1=anti-acid production; ST2=anti-bloating/anti-constipation agent; ST3=multitarget/ herbal agents; ST4=anti-diarrheal (anti-peristaltic); ST5=analgesic (NSAID); ST6=anti-emetic (central); ST7=anti-emetic (pro-kinetic); ST8=antacid; ST9=other; ST10=laxative (pro-kinetic). Overall GI events were reported in the second day after the dose. Relative day for Overall GI events = assessment date-first dose date. |
| Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS) | Up to Week 12 | The MOGISS is a questionnaire about the severity of overall gastrointestinal-related events, including specifically symptoms of nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence for 24 hours before the AM dose. Participants who rated the intensity of symptoms reported on the MOGISS and included each symptomatic therapy used in the eDiary are presented. |
| Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS) | Up to Week 12 | The MAGISS is a questionnaire in which participants reported overall acute gastrointestinal-related events, (especially symptoms of nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) for each 10 hours after the AM and PM doses of study drug. Participants who rated the intensity of gastrointestinal-related events reported on MAGISS, included the duration of the gastrointestinal-related events and each symptomatic therapy used in the eDiary are presented. |
| Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Up to Week 12 | The MOGISS is a questionnaire about overall events related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. MOGISS is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. The worst overall severity score for gastrointestinal-related events was calculated for each participant for the overall treatment period of 12 weeks, and for each 4-week period therein. |
| Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Up to Week 12 | The MAGISS is a questionnaire about the overall events related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) following drug administration (acute symptoms). MAGISS is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. The worst overall severity score for gastrointestinal-related events was calculated for each participant for the overall treatment period of 12 weeks, and for each 4-week period therein. |
| Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Up to Week 12 | The percentage of days with GI events as reported on MOGISS was calculated for each participant and each analysis period using the following formula: 100 x (# of days with \[GI\] events / # of days tolerability scale completed). The symptomatic therapy (ST) categories were provided by Biogen Medical team as follows: ST1=anti-acid production; ST2=anti-bloating/anti-constipation agent; ST3=multitarget/ herbal agents; ST4=anti-diarrheal (anti-peristaltic); ST5=analgesic (NSAID); ST6=anti-emetic (central); ST7=anti-emetic (pro-kinetic); ST8=antacid; ST9=other; ST10=laxative (pro-kinetic). Overall GI events were reported in the second day after the dose. Relative day for Overall GI events = assessment date-first dose date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Up to Week 12 | Symptomatic therapies were classified into 10 main categories: anti-acid production (eg, pantoprazole, omeprazole, esomeprazole, ranitidine); anti-bloating/anti-constipation agents (eg, hyoscine butylbromide, sodium picosulfate, Agiolax, dimeticone, lactulose, Movicol, simethicone); multitarget/herbal agents (includes Iberogast, Gaviscon, amaratropfen, Wikalin, Gaviscon & Iberogast, Iberogast & Wikalin); anti-diarrheal (anti-peristaltic; loperamide, racecadotril); analgesic (non-steroidal anti-inflammatory drug \[NSAID\]; ibuprofen, paracetamol, metamizole); anti-emetic (central; dimenhydrinate, domperidone); anti-emetic (pro-kinetic; metoclopramide); anti-acid (calcium carbonate, magaldrate, sodium hydrogen carbonate, sodium hydroxide/aluminium oxide, Talcid); other (Saccharomyces boulardii, carbon tablet, Lactobacillus acidophilus); laxative (pro-kinetic; bisacodyl). Participants may have taken \> 1 symptomatic therapy but were counted only once for the 'All therapies' summary. |
| Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Up to Week 12 | Symptomatic therapies were classified into 10 categories: anti-acid production (eg, pantoprazole, omeprazole, esomeprazole, ranitidine); anti-bloating/anti-constipation agents (eg, hyoscine butylbromide, sodium picosulfate, Agiolax, dimeticone, lactulose, Movicol, simethicone); multitarget/herbal agents (eg, Iberogast, Gaviscon, amaratropfen, Wikalin, Gaviscon & Iberogast, Iberogast & Wikalin); anti-diarrheal (anti-peristaltic; loperamide, racecadotril); analgesic (NSAID; ibuprofen, paracetamol, metamizole); anti-emetic (central; dimenhydrinate, domperidone); anti-emetic (pro-kinetic; metoclopramide); anti-acid (calcium carbonate, magaldrate, sodium hydrogen carbonate, sodium hydroxide/aluminium oxide, Talcid); other (Saccharomyces boulardii, carbon tablet, Lactobacillus acidophilus); laxative (pro-kinetic; bisacodyl). If a participant had multiple different therapies on the same day, the days on symptomatic therapy was calculated as 1 day in 'All therapies'. |
| Percentage of Participants Who Required Dimethyl Fumarate Dose Reduction In Response To Gastrointestinal-Related Events | Up to Week 12 | Dose reductions are defined as participants who take any dimethyl fumarate 120 mg or 0 mg since initiation of dimethyl fumarate 240 mg. |
| Percentage of Participants Who Discontinued Dimethyl Fumarate Due To Gastrointestinal-Related Treatment-Emergent Adverse Events | Up to Week 12 | — |
| Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12 | Week 4, Week 8, Week 12 | The cumulative percentage of dimethyl fumarate-treated participants with relapsing-remitting multiple sclerosis who required symptomatic therapy up to Week 4, Week 8, and Week 12 were estimated using the Kaplan-Meier method. |
Countries
Germany
Participant flow
Pre-assignment details
A total of 214 participants were screened and enrolled; 3 participants did not receive study drug (1 withdrew consent and 2 did not meet all inclusion/exclusion criteria). A total of 211 participants were included in the safety population.
Participants by arm
| Arm | Count |
|---|---|
| Dimethyl Fumarate Dimethyl fumarate administered orally at 120 mg BID for the first 7 days and 240 mg BID thereafter for a total of 12 weeks. | 211 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Consent Withdrawn | 4 |
| Overall Study | Investigator Decision | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 4 |
Baseline characteristics
| Characteristic | Dimethyl Fumarate |
|---|---|
| Age, Continuous | 40.09 years STANDARD_DEVIATION 10.97 |
| Sex: Female, Male Female | 149 Participants |
| Sex: Female, Male Male | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 129 / 211 |
| serious Total, serious adverse events | 5 / 211 |
Outcome results
Primary
Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS
The percentage of days with GI events as reported on MOGISS was calculated for each participant and each analysis period using the following formula: 100 x (# of days with \[GI\] events / # of days tolerability scale completed). The symptomatic therapy (ST) categories were provided by Biogen Medical team as follows: ST1=anti-acid production; ST2=anti-bloating/anti-constipation agent; ST3=multitarget/ herbal agents; ST4=anti-diarrheal (anti-peristaltic); ST5=analgesic (NSAID); ST6=anti-emetic (central); ST7=anti-emetic (pro-kinetic); ST8=antacid; ST9=other; ST10=laxative (pro-kinetic). Overall GI events were reported in the second day after the dose. Relative day for Overall GI events = assessment date-first dose date.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy; n=participants with an evaluable assessment during given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; Any ST (n=84) | 38.13 percentage of days | Standard Deviation 29.263 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST1 (n=50) | 42.08 percentage of days | Standard Deviation 27.495 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST2 (n=26) | 36.98 percentage of days | Standard Deviation 29.754 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST3 (n=20) | 39.61 percentage of days | Standard Deviation 29.197 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST4 (n=16) | 48.15 percentage of days | Standard Deviation 30.14 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST5 (n=10) | 45.94 percentage of days | Standard Deviation 27.147 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST6 (n=8) | 44.33 percentage of days | Standard Deviation 29.095 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST7 (n=6) | 57.52 percentage of days | Standard Deviation 21.998 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST8 (n=5) | 52.71 percentage of days | Standard Deviation 31.829 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST9 (n=3) | 32.78 percentage of days | Standard Deviation 26.995 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; ST10 (n=2) | 9.20 percentage of days | Standard Deviation 2.137 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; Any ST (n=73) | 49.58 percentage of days | Standard Deviation 29.547 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST1 (n=44) | 53.92 percentage of days | Standard Deviation 27.197 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST2 (n=23) | 49.53 percentage of days | Standard Deviation 32.012 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST3 (n=18) | 55.31 percentage of days | Standard Deviation 29.869 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST4 (n=13) | 56.63 percentage of days | Standard Deviation 25.764 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST5 (n=9) | 44.42 percentage of days | Standard Deviation 32.47 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST6 (n=6) | 48.48 percentage of days | Standard Deviation 35.539 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST7 (n=6) | 69.78 percentage of days | Standard Deviation 24.808 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST8 (n=5) | 66.43 percentage of days | Standard Deviation 31.4 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST9 (n=3) | 41.41 percentage of days | Standard Deviation 34.085 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; ST10 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; Any ST (n=38) | 41.55 percentage of days | Standard Deviation 38.612 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST1 (n=23) | 44.04 percentage of days | Standard Deviation 41.414 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST2 (n=3) | 41.67 percentage of days | Standard Deviation 52.042 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST3 (n=8) | 37.45 percentage of days | Standard Deviation 37.388 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST4 (n=3) | 69.14 percentage of days | Standard Deviation 44.186 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST5 (n=3) | 63.75 percentage of days | Standard Deviation 31.332 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST6 (n=3) | 70.42 percentage of days | Standard Deviation 25.699 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST7 (n=1) | 35.71 percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST8 (n=2) | 56.88 percentage of days | Standard Deviation 40.032 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST9 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; ST10 (n=2) | 1.79 percentage of days | Standard Deviation 2.525 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; Any ST (n=29) | 43.27 percentage of days | Standard Deviation 42.322 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST1 (n=15) | 47.66 percentage of days | Standard Deviation 43.191 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST2 (n=3) | 82.72 percentage of days | Standard Deviation 29.937 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST3 (n=6) | 48.85 percentage of days | Standard Deviation 50.931 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST4 (n=4) | 22.12 percentage of days | Standard Deviation 20.834 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST5 (n=2) | 62.50 percentage of days | Standard Deviation 53.033 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST6 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST7 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST8 (n=2) | 9.26 percentage of days | Standard Deviation 13.095 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST9 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; ST10 (n=0) | NA percentage of days | — |
Primary
Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS
Percentage of days with GI events as reported on MAGISS was calculated for each participant and each analysis period using the following formula: 100 x (# of days with \[GI\] events / # of days tolerability scale completed). The ST categories were provided by Biogen Medical team as follows: ST1=anti-acid production; ST2=anti-bloating/anti-constipation agent; ST3=multitarget/ herbal agents; ST4=anti-diarrheal (anti-peristaltic); ST5=analgesic (NSAID); ST6=anti-emetic (central); ST7=anti-emetic (pro-kinetic); ST8=antacid; ST9=other; ST10=laxative (pro-kinetic). Overall GI events were reported in the second day after the dose. Relative day for Overall GI events = assessment date-first dose date.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy; n=participants with an evaluable assessment during given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; Any ST (n=84) | 38.20 percentage of days | Standard Deviation 30.516 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST1 (n=50) | 41.29 percentage of days | Standard Deviation 29.517 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST2 (n=26) | 33.67 percentage of days | Standard Deviation 27.31 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST3 (n=20) | 39.28 percentage of days | Standard Deviation 29.165 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST4 (n=16) | 49.94 percentage of days | Standard Deviation 33.291 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST5 (n=10) | 45.65 percentage of days | Standard Deviation 27.118 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST6 (n=8) | 44.71 percentage of days | Standard Deviation 30.374 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST7 (n=6) | 55.32 percentage of days | Standard Deviation 23.097 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST8 (n=5) | 53.42 percentage of days | Standard Deviation 31.443 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST9 (n=3) | 36.92 percentage of days | Standard Deviation 27.8 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; ST10 (n=2) | 10.88 percentage of days | Standard Deviation 1.924 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; Any ST (n=73) | 51.03 percentage of days | Standard Deviation 30.36 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST1 (n=44) | 54.41 percentage of days | Standard Deviation 29.608 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST2 (n=23) | 47.84 percentage of days | Standard Deviation 30.764 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST3 (n=18) | 56.67 percentage of days | Standard Deviation 30.711 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST4 (n=13) | 58.90 percentage of days | Standard Deviation 27.111 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST5 (n=9) | 53.74 percentage of days | Standard Deviation 32.304 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST6 (n=6) | 46.43 percentage of days | Standard Deviation 33.221 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST7 (n=6) | 67.54 percentage of days | Standard Deviation 25.296 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST8 (n=5) | 69.86 percentage of days | Standard Deviation 28.919 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST9 (n=3) | 47.61 percentage of days | Standard Deviation 47.61 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; ST10 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; Any ST (n=38) | 40.59 percentage of days | Standard Deviation 37.836 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST1 (n=23) | 41.59 percentage of days | Standard Deviation 41.442 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST2 (n=3) | 47.14 percentage of days | Standard Deviation 45.781 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST3 (n=8) | 38.50 percentage of days | Standard Deviation 35.493 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST4 (n=3) | 62.58 percentage of days | Standard Deviation 45.775 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST5 (n=3) | 56.33 percentage of days | Standard Deviation 33.011 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST6 (n=3) | 71.61 percentage of days | Standard Deviation 24.587 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST7 (n=1) | 35.71 percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST8 (n=2) | 62.24 percentage of days | Standard Deviation 32.456 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST9 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; ST10 (n=2) | 10.00 percentage of days | Standard Deviation 14.142 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; Any ST (n=29) | 41.28 percentage of days | Standard Deviation 42.466 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST1 (n=15) | 44.24 percentage of days | Standard Deviation 44.754 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST2 (n=3) | 76.19 percentage of days | Standard Deviation 41.239 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST3 (n=6) | 51.99 percentage of days | Standard Deviation 50.113 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST4 (n=4) | 15.48 percentage of days | Standard Deviation 10.178 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST5 (n=2) | 63.16 percentage of days | Standard Deviation 52.103 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST6 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST7 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST8 (n=2) | 13.11 percentage of days | Standard Deviation 7.655 |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST9 (n=0) | NA percentage of days | — |
| Dimethyl Fumarate | Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; ST10 (n=0) | NA percentage of days | — |
Primary
Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS)
The MAGISS is a questionnaire in which participants reported overall acute gastrointestinal-related events, (especially symptoms of nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) for each 10 hours after the AM and PM doses of study drug. Participants who rated the intensity of gastrointestinal-related events reported on MAGISS, included the duration of the gastrointestinal-related events and each symptomatic therapy used in the eDiary are presented.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate; n=participants with an assessment during given time period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS) | Overall Treatment Period; n=211 | 83 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS) | Weeks 1-4; n=211 | 72 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS) | Weeks 5-8; n=189 | 34 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS) | Weeks 9-12; n=180 | 26 Participants |
Primary
Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS)
The MOGISS is a questionnaire about the severity of overall gastrointestinal-related events, including specifically symptoms of nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence for 24 hours before the AM dose. Participants who rated the intensity of symptoms reported on the MOGISS and included each symptomatic therapy used in the eDiary are presented.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate; n=participants with an assessment during given time period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS) | Overall Treatment Period; n=211 | 82 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS) | Weeks 1-4; n=211 | 71 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS) | Weeks 5-8; n=186 | 33 Participants |
| Dimethyl Fumarate | Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS) | Weeks 9-12; n=178 | 22 Participants |
Primary
Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS
The MAGISS is a questionnaire about the overall events related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) following drug administration (acute symptoms). MAGISS is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. The worst overall severity score for gastrointestinal-related events was calculated for each participant for the overall treatment period of 12 weeks, and for each 4-week period therein.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy; n=participants with an evaluable assessment during given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Overall treatment period; n=84 | 5.93 units on a scale | Standard Deviation 2.516 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 1-4; n=73 | 5.88 units on a scale | Standard Deviation 2.614 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 5-8; n=39 | 3.31 units on a scale | Standard Deviation 2.307 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS | Week 9-12; n=29 | 3.55 units on a scale | Standard Deviation 2.772 |
Primary
Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS
The MOGISS is a questionnaire about overall events related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. MOGISS is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. The worst overall severity score for gastrointestinal-related events was calculated for each participant for the overall treatment period of 12 weeks, and for each 4-week period therein.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy; n=participants with an evaluable assessment during given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Overall treatment period; n=84 | 5.94 units on a scale | Standard Deviation 2.427 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 1-4; n=73 | 5.75 units on a scale | Standard Deviation 2.554 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 5-8; n=38 | 3.53 units on a scale | Standard Deviation 2.533 |
| Dimethyl Fumarate | Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS | Week 9-12; n=29 | 3.1 units on a scale | Standard Deviation 2.568 |
Secondary
Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category
Symptomatic therapies were classified into 10 categories: anti-acid production (eg, pantoprazole, omeprazole, esomeprazole, ranitidine); anti-bloating/anti-constipation agents (eg, hyoscine butylbromide, sodium picosulfate, Agiolax, dimeticone, lactulose, Movicol, simethicone); multitarget/herbal agents (eg, Iberogast, Gaviscon, amaratropfen, Wikalin, Gaviscon & Iberogast, Iberogast & Wikalin); anti-diarrheal (anti-peristaltic; loperamide, racecadotril); analgesic (NSAID; ibuprofen, paracetamol, metamizole); anti-emetic (central; dimenhydrinate, domperidone); anti-emetic (pro-kinetic; metoclopramide); anti-acid (calcium carbonate, magaldrate, sodium hydrogen carbonate, sodium hydroxide/aluminium oxide, Talcid); other (Saccharomyces boulardii, carbon tablet, Lactobacillus acidophilus); laxative (pro-kinetic; bisacodyl). If a participant had multiple different therapies on the same day, the days on symptomatic therapy was calculated as 1 day in 'All therapies'.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy; n=participants with an evaluable assessment during given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: All therapies; n=84 | 13.15 days | Standard Deviation 19.21 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-acid production; n=50 | 16.62 days | Standard Deviation 22.21 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-bloating/anti-constipation agent; n=26 | 2.42 days | Standard Deviation 1.81 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Multi-target/herbal agents; n=20 | 9.40 days | Standard Deviation 13.95 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-diarrheal (anti-peristaltic); n=16 | 3.13 days | Standard Deviation 2.53 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Analgesic (NSAID); n=10 | 3.10 days | Standard Deviation 1.73 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-emetic (central); n=8 | 3.25 days | Standard Deviation 4.43 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-emetic (pro-kinetic); n=6 | 1.83 days | Standard Deviation 0.98 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Antacid; n=5 | 3.60 days | Standard Deviation 4.22 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Other; n=3 | 1.67 days | Standard Deviation 0.58 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Laxative (pro-kinetic); n=2 | 1.00 days | Standard Deviation 0 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: All therapies; n=73 | 6.03 days | Standard Deviation 6.12 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-acid production; n=44 | 7.07 days | Standard Deviation 6.73 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-bloating/anti-constipation; n=23 | 2.30 days | Standard Deviation 1.89 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Multi-target/herbal agents; n=18 | 3.78 days | Standard Deviation 3.06 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-diarrheal (anti-peristaltic); n=13 | 2.62 days | Standard Deviation 1.45 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Analgesic (NSAID); n=9 | 2.11 days | Standard Deviation 0.93 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-emetic (central); n=6 | 3.17 days | Standard Deviation 3.92 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-emetic (pro-kinetic); n=6 | 1.67 days | Standard Deviation 0.82 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Antacid; n=5 | 1.80 days | Standard Deviation 1.3 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Other; n=3 | 1.67 days | Standard Deviation 0.58 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: All therapies; n=38 | 10.08 days | Standard Deviation 10.56 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-acid production; n=23 | 13.00 days | Standard Deviation 11.14 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Multi-target/herbal agents; n=8 | 8.50 days | Standard Deviation 10.45 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Analgesic (NSAID); n=3 | 2.00 days | Standard Deviation 1 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-bloating/anti-constipation; n=3 | 1.33 days | Standard Deviation 0.58 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-diarrheal (anti-peristaltic); n=3 | 4.00 days | Standard Deviation 3.61 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-emetic (central); n=3 | 2.33 days | Standard Deviation 1.15 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Antacid; n=2 | 2.50 days | Standard Deviation 2.12 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Laxative (pro-kinetic); n=2 | 1.00 days | Standard Deviation 0 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-emetic (prokinetic); n=1 | 1.00 days | — |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: All therapies; n=29 | 9.72 days | Standard Deviation 10.31 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-acid production; n=15 | 14.73 days | Standard Deviation 10.91 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Multi-target/herbal agents; n=6 | 8.67 days | Standard Deviation 8.57 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-diarrheal (anti-peristaltic); n=4 | 1.00 days | Standard Deviation 0 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-bloating/anti-constipation; n=3 | 2.00 days | Standard Deviation 1 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Analgesic (NSAID); n=2 | 3.00 days | Standard Deviation 0 |
| Dimethyl Fumarate | Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Antacid; n=2 | 2.00 days | Standard Deviation 1.41 |
Secondary
Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category
Symptomatic therapies were classified into 10 main categories: anti-acid production (eg, pantoprazole, omeprazole, esomeprazole, ranitidine); anti-bloating/anti-constipation agents (eg, hyoscine butylbromide, sodium picosulfate, Agiolax, dimeticone, lactulose, Movicol, simethicone); multitarget/herbal agents (includes Iberogast, Gaviscon, amaratropfen, Wikalin, Gaviscon & Iberogast, Iberogast & Wikalin); anti-diarrheal (anti-peristaltic; loperamide, racecadotril); analgesic (non-steroidal anti-inflammatory drug \[NSAID\]; ibuprofen, paracetamol, metamizole); anti-emetic (central; dimenhydrinate, domperidone); anti-emetic (pro-kinetic; metoclopramide); anti-acid (calcium carbonate, magaldrate, sodium hydrogen carbonate, sodium hydroxide/aluminium oxide, Talcid); other (Saccharomyces boulardii, carbon tablet, Lactobacillus acidophilus); laxative (pro-kinetic; bisacodyl). Participants may have taken \> 1 symptomatic therapy but were counted only once for the 'All therapies' summary.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: All therapies | 38 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Overall treatment period (OTP): All therapies | 84 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-acid production | 50 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-bloating/anti-constipation agent | 26 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Multi-target/herbal agents | 20 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-diarrheal (anti-peristaltic) | 16 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Analgesic (NSAID) | 10 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-emetic (central) | 8 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Anti-emetic (pro-kinetic) | 6 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Antacid | 5 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Other | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | OTP: Laxative (pro-kinetic) | 2 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: All therapies | 73 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-acid production | 44 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-bloating/anti-constipation agent | 23 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Multi-target/herbal agents | 18 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-diarrheal (anti-peristaltic) | 13 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Analgesic (NSAID) | 9 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-emetic (central) | 6 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Anti-emetic (pro-kinetic) | 6 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Antacid | 5 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 1-4: Other | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-acid production | 23 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Multi-target/herbal agents | 8 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Analgesic (NSAID) | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-bloating/anti-constipation agent | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-diarrheal (anti-peristaltic) | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-emetic (central) | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Antacid | 2 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Laxative (pro-kinetic) | 2 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 5-8: Anti-emetic (pro-kinetic) | 1 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: All therapies | 29 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-acid production | 15 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Multi-target/herbal agents | 6 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-diarrheal (anti-peristaltic) | 4 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Anti-bloating.anti-constipation agent | 3 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Analgesic (NSAID) | 2 participants |
| Dimethyl Fumarate | Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category | Week 9-12: Antacid | 2 participants |
Secondary
Percentage of Participants Who Discontinued Dimethyl Fumarate Due To Gastrointestinal-Related Treatment-Emergent Adverse Events
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimethyl Fumarate | Percentage of Participants Who Discontinued Dimethyl Fumarate Due To Gastrointestinal-Related Treatment-Emergent Adverse Events | 6.6 percentage of participants |
Secondary
Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12
The cumulative percentage of dimethyl fumarate-treated participants with relapsing-remitting multiple sclerosis who required symptomatic therapy up to Week 4, Week 8, and Week 12 were estimated using the Kaplan-Meier method.
Time frame: Week 4, Week 8, Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate and used symptomatic therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimethyl Fumarate | Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12 | Week 4 | 35.3 percentage of participants |
| Dimethyl Fumarate | Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12 | Week 8 | 38.4 percentage of participants |
| Dimethyl Fumarate | Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12 | Week 12 | 41.1 percentage of participants |
Secondary
Percentage of Participants Who Required Dimethyl Fumarate Dose Reduction In Response To Gastrointestinal-Related Events
Dose reductions are defined as participants who take any dimethyl fumarate 120 mg or 0 mg since initiation of dimethyl fumarate 240 mg.
Time frame: Up to Week 12
Population: Safety Population: all participants who received at least 1 dose of dimethyl fumarate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimethyl Fumarate | Percentage of Participants Who Required Dimethyl Fumarate Dose Reduction In Response To Gastrointestinal-Related Events | 34.6 percentage of participants |