Study of Montelukast on Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera (MITIGATE)

March 20, 2020 updated by: Biogen

A Multicenter, Double- Blind, Placebo- Controlled Study of Montelukast on Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera® (Dimethyl Fumarate) Delayed Release Capsules

The primary objective of this study is to evaluate whether montelukast can reduce the severity of gastrointestinal (GI) events, measured by the Gastrointestinal Symptom Rating Scale (GSRS), after oral administration of dimethyl fumarate (DMF) in participants with relapsing forms of Multiple Sclerosis (MS). The secondary objectives of this study are as follows: To evaluate whether montelukast after oral administration of DMF in participants with relapsing forms of MS decreases discontinuations due to GI events and reduces the number of participants taking symptomatic therapies for GI events; To investigate the effect of montelukast on the incidence of flushing events after oral administration of 240 mg DMF in participants with relapsing forms of MS.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • Research Site
    • California
      • Carmichael, California, United States, 95608
        • Research Site
      • La Jolla, California, United States, 92037
        • Research Site
      • La Mesa, California, United States, 91942
        • Research Site
      • Pomona, California, United States, 91767
        • Research Site
      • Simi Valley, California, United States, 93065
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
      • Colorado Springs, Colorado, United States, 80907
        • Research Site
    • Connecticut
      • Fairfield, Connecticut, United States, 06824
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Research Site
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Research Site
      • Naples, Florida, United States, 34102
        • Research Site
      • Ormond Beach, Florida, United States, 32174-3102
        • Research Site
      • Sunrise, Florida, United States, 33351
        • Research Site
    • Georgia
      • Rome, Georgia, United States, 30165-1625
        • Research Site
      • Smyrna, Georgia, United States, 30269
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Research Site
      • Flossmoor, Illinois, United States, 60422
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46256
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Research Site
    • Maine
      • Scarborough, Maine, United States, 04074
        • Research Site
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Research Site
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Research Site
      • Kansas City, Missouri, United States, 64111
        • Research Site
      • Saint Louis, Missouri, United States, 63104
        • Research Site
    • New Jersey
      • Freehold, New Jersey, United States, 07728
        • Research Site
    • New York
      • Amherst, New York, United States, 14226
        • Research Site
      • New York, New York, United States, 10029
        • Research Site
      • Patchogue, New York, United States, 11772
        • Research Site
    • North Carolina
      • Hendersonville, North Carolina, United States, 28792
        • Research Site
      • Raleigh, North Carolina, United States, 27607-6010
        • Research Site
      • Sanford, North Carolina, United States, 27330
        • Research Site
      • Winston-Salem, North Carolina, United States, 27103
        • Research Site
    • Ohio
      • Dayton, Ohio, United States, 45417
        • Research Site
      • Dayton, Ohio, United States, 45459
        • Research Site
      • Uniontown, Ohio, United States, 44685
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73109
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97225
        • Research Site
      • Tualatin, Oregon, United States, 97062
        • Research Site
    • Pennsylvania
      • Dickson City, Pennsylvania, United States, 18519
        • Research Site
      • Greensburg, Pennsylvania, United States, 15601
        • Research Site
      • Hershey, Pennsylvania, United States, 17033
        • Research Site
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37215
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75214
        • Research Site
      • Round Rock, Texas, United States, 78681
        • Research Site
    • Virginia
      • Alexandria, Virginia, United States, 22310
        • Research Site
      • Newport News, Virginia, United States, 23601
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98122
        • Research Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Reside in the United States and have a confirmed diagnosis of a relapsing form of MS and satisfy the therapeutic indication as described in the local label
  • As perceived by the Investigator, have the ability to comply with all requirements of the study protocol and to operate the eDiary required to record GI-related events
  • Female participants of childbearing potential who are not surgically sterile must practice effective contraception during their participation in the study and be willing and able to continue contraception for 30 days after they complete or withdraw from the study. All men must practice effective contraception, and they should not donate sperm throughout the study and for at least 90 days after their last dose of study treatment.

Key Exclusion Criteria:

  • History of significant GI disease (for example, irritable bowel disease, peptic ulcer disease, history of major GI surgery, eosinophilic GI disease, or food allergies)
  • Chronic use (≥7 consecutive days) of bismuth subsalicylate, simethicone, calcium carbonate, loperamide, proton-pump inhibitors, or ondansetron within 1 month prior to the Screening Visit
  • Use of the following medications: montelukast, immunotherapy, mast cell stabilizers, or parenteral, inhaled, or oral steroids up to 1 month prior to the Screening Visit. Use of these medications is also not permitted for the duration of the study (except for the use of montelukast as per study protocol) and will lead to discontinuation
  • Have one or more major comorbidities that, in the opinion of the Investigator, may affect the outcome of the study
  • History of malignancy (except for basal cell carcinoma that had been completely excised prior to study entry), severe allergic or anaphylactic reactions or known drug hypersensitivity, abnormal laboratory results indicative of any significant disease, and/or a major disease that would preclude participation in a clinical study

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: DMF plus montelukast
DMF as described in the United States Prescribing Information (USPI) plus 10mg montelukast tablet once daily according to the prevailing product label (Singulair)
Drug: dimethyl fumarate
Starting dose of 120 mg twice daily orally After 7 days, maintenance dose of 240 mg twice daily orally
Other Names:
  • BG00012
  • DMF
  • Tecfidera
Drug: montelukast
As described in the treatment arm
Other Names:
  • Singulair
Experimental: DMF plus placebo
DMF as described in the USPI plus matched placebo
Drug: Placebo
Matched placebo
Drug: dimethyl fumarate
Starting dose of 120 mg twice daily orally After 7 days, maintenance dose of 240 mg twice daily orally
Other Names:
  • BG00012
  • DMF
  • Tecfidera

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10
Time Frame: Baseline (Day 0), Day 10 (10 days after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Worsening in severity was defined as a positive average change from baseline (Day 0) to Day 10 in the GSRS score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Average change is the sum of changes from baseline in GSRS score over the first 10 days divided by the total of days with a GSRS score.
Baseline (Day 0), Day 10 (10 days after Day 0)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10
Time Frame: Baseline (Day 0), Day 1 (1 day after Day 0), Day 10 (10 days after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased.
Baseline (Day 0), Day 1 (1 day after Day 0), Day 10 (10 days after Day 0)
Average Change From Baseline in GSRS Overall Score at Day 1 to Week 10
Time Frame: Baseline (Day 0), Day 1 (1 day after Day 0), Week 10 (10 weeks after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and Week 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased.
Baseline (Day 0), Day 1 (1 day after Day 0), Week 10 (10 weeks after Day 0)
Time to First Worsening From Baseline in GSRS Overall Score at Day 1 to Day 10
Time Frame: Baseline (Day 0), Day 1 (1 day after Day 0) to Day 10 (10 days after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose.. Time to the first worsening was defined as the number of days from Day 1 to the first date with a worsened GSRS score. Censoring occurred at Day 10.
Baseline (Day 0), Day 1 (1 day after Day 0) to Day 10 (10 days after Day 0)
Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8
Time Frame: Baseline (Day 0), Day 1 (1 Day after Day 0) to Week 8 (8 weeks after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Recovery was defined as a GSRS score less than or equal to the Day 0 score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Time to recovery was defined as the date of recovery minus the date of the last occurrence of the worst score.
Baseline (Day 0), Day 1 (1 Day after Day 0) to Week 8 (8 weeks after Day 0)
Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8
Time Frame: Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and the specified time point. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased.
Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0)
Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment
Time Frame: Baseline (Day 0), Day 3 (72 hours after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 3. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 is the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased.
Baseline (Day 0), Day 3 (72 hours after Day 0)
Percentage of Participants Who Required GI Symptomatic Therapy During the Study
Time Frame: Day 10 to Week 10
Symptomatic therapies were not permitted during the first 10 days after starting montelukast or placebo. From Day 10 onward, participants were allowed to use the following symptomatic therapies to treat DMF-related GI events: bismuth subsalicylate, simethicone, calcium carbonate, loperamide, proton-pump inhibitors and ondansetron.
Day 10 to Week 10
Percentage of Participants Who Discontinued DMF Therapy Due to GI-Related Adverse Events (AEs) From Day 0 to Week 10
Time Frame: Day 0 to Week 10
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Participants used an electronic diary to record GI-related events. GI-related AEs included diarrhea, nausea, upper abdominal pain, abdominal pain, and dyspepsia.
Day 0 to Week 10
Percentage of Participants Who Experienced AEs Related to Flushing
Time Frame: Day of first DMF dose (up to 27 days before Day 0) to Week 10
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Flushing-related AEs included flushing and hot flush. Only events with an onset date on or after the date of first DMF dose (up to 27 days before Day 0) are presented. This includes events present before and subsequently worsened after the first dose of DMF.
Day of first DMF dose (up to 27 days before Day 0) to Week 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 12, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 16, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 27, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 109MS414

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Sclerosis

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings