Gastrointestinal Tolerability Study Of Dimethyl Fumarate In Participants With Relapsing-Remitting Multiple Sclerosis In Germany

NCT02125604 | Completed Phase 4 Results

• 2 other identifiers: 109MS4072013-001486-17
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 19

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.

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Gastrointestinal event

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to Week 12

• 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.

  Up to Week 12

• 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.

  Up to Week 12

• 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.

  Up to Week 12

• 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.

  Up to Week 12

• 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.

  Up to Week 12

Secondary Outcomes (5)

• Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12

  Week 4, Week 8, Week 12

• Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category

  Up to Week 12

• Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category

  Up to Week 12

• Percentage of Participants Who Required Dimethyl Fumarate Dose Reduction In Response To Gastrointestinal-Related Events

  Up to Week 12

• Percentage of Participants Who Discontinued Dimethyl Fumarate Due To Gastrointestinal-Related Treatment-Emergent Adverse Events

  Up to Week 12

Study Arms (1)

Dimethyl Fumarate

EXPERIMENTAL

Dimethyl fumarate administered orally at 120 mg twice daily (BID) for the first 7 days and 240 mg BID thereafter for a total of 12 weeks.

Drug: dimethyl fumarate

Interventions

dimethyl fumarate DRUG

capsules administered according to the prevailing product label

Also known as: BG00012, Tecfidera, DMF

Dimethyl Fumarate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (19)

Research Site

Augsburg, Germany

Location

Research Site

Bamburg, Germany

Location

Research Site

Bayreuth, Germany

Location

Research Site

Berlin, Germany

Location

Research Site

Bochum, Germany

Location

Research Site

Bonn, Germany

Location

Research Site

Erbach im Odenwald, Germany

Location

Research Site

Erlangen, Germany

Location

Research Site

Freiburg im Breisgau, Germany

Location

Research Site

Hamburg, Germany

Location

Research Site

Leipzig, Germany

Location

Research Site

Marburg, Germany

Location

Research Site

Minden, Germany

Location

Research Site

Mittweida, Germany

Location

Research Site

München, Germany

Location

Research Site

Münster, Germany

Location

Research Site

Osnabrück, Germany

Location

Research Site

Potsdam, Germany

Location

Research Site

Siegen, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2014
• First Posted: April 29, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 18, 2017
• Results First Posted: April 18, 2017

Record last verified: 2017-03

Locations

DE (19)