NCT02410278

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
102

participants targeted

Target at P50-P75 for phase_4 multiple-sclerosis

Timeline
Completed

Started Mar 2015

Geographic Reach
1 country

50 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 12, 2015

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

April 2, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 7, 2015

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 16, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 27, 2017

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

July 24, 2018

Completed
Last Updated

March 31, 2020

Status Verified

March 1, 2020

Enrollment Period

1.9 years

First QC Date

April 2, 2015

Results QC Date

April 27, 2018

Last Update Submit

March 20, 2020

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10

    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 Outcomes (9)

  • Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10

    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

    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

    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

    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

    Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0)

  • +4 more secondary outcomes

Study Arms (2)

DMF plus montelukast

EXPERIMENTAL

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 fumarateDrug: montelukast

DMF plus placebo

EXPERIMENTAL

DMF as described in the USPI plus matched placebo

Drug: dimethyl fumarateDrug: Placebo

Interventions

Starting dose of 120 mg twice daily orally After 7 days, maintenance dose of 240 mg twice daily orally

Also known as: BG00012, Tecfidera, DMF
DMF plus montelukastDMF plus placebo

As described in the treatment arm

Also known as: Singulair
DMF plus montelukast

Matched placebo

DMF plus placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (50)

Research Site

Jonesboro, Arkansas, 72401, United States

Location

Research Site

Carmichael, California, 95608, United States

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Research Site

La Jolla, California, 92037, United States

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Research Site

La Mesa, California, 91942, United States

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Research Site

Pomona, California, 91767, United States

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Research Site

Simi Valley, California, 93065, United States

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Research Site

Aurora, Colorado, 80045, United States

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Research Site

Colorado Springs, Colorado, 80907, United States

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Research Site

Fairfield, Connecticut, 06824, United States

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Research Site

Washington D.C., District of Columbia, 20057, United States

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Research Site

Jacksonville, Florida, 32216, United States

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Research Site

Naples, Florida, 34102, United States

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Research Site

Ormond Beach, Florida, 32174-3102, United States

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Research Site

Sunrise, Florida, 33351, United States

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Research Site

Rome, Georgia, 30165-1625, United States

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Research Site

Smyrna, Georgia, 30269, United States

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Research Site

Chicago, Illinois, 60612, United States

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Research Site

Flossmoor, Illinois, 60422, United States

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Research Site

Indianapolis, Indiana, 46256, United States

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Research Site

Louisville, Kentucky, 40207, United States

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Research Site

Scarborough, Maine, 04074, United States

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Research Site

Farmington Hills, Michigan, 48334, United States

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Research Site

Chesterfield, Missouri, 63017, United States

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Research Site

Kansas City, Missouri, 64111, United States

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Research Site

St Louis, Missouri, 63104, United States

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Research Site

Freehold, New Jersey, 07728, United States

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Research Site

Amherst, New York, 14226, United States

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Research Site

New York, New York, 10029, United States

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Research Site

Patchogue, New York, 11772, United States

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Research Site

Hendersonville, North Carolina, 28792, United States

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Research Site

Raleigh, North Carolina, 27607-6010, United States

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Research Site

Sanford, North Carolina, 27330, United States

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Research Site

Winston-Salem, North Carolina, 27103, United States

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Research Site

Dayton, Ohio, 45417, United States

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Research Site

Dayton, Ohio, 45459, United States

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Research Site

Uniontown, Ohio, 44685, United States

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Research Site

Oklahoma City, Oklahoma, 73109, United States

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Research Site

Portland, Oregon, 97225, United States

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Research Site

Tualatin, Oregon, 97062, United States

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Research Site

Dickson City, Pennsylvania, 18519, United States

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Research Site

Greensburg, Pennsylvania, 15601, United States

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Research Site

Hershey, Pennsylvania, 17033, United States

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Research Site

Wilkes-Barre, Pennsylvania, 18711, United States

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Research Site

Nashville, Tennessee, 37215, United States

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Research Site

Dallas, Texas, 75214, United States

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Research Site

Round Rock, Texas, 78681, United States

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Research Site

Alexandria, Virginia, 22310, United States

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Research Site

Newport News, Virginia, 23601, United States

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Research Site

Seattle, Washington, 98122, United States

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Research Site

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Dimethyl Fumaratemontelukast

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

FumaratesDicarboxylic AcidsAcids, AcyclicCarboxylic AcidsOrganic Chemicals

Results Point of Contact

Title
Biogen Study Medical Director
Organization
Biogen

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
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2015

First Posted

April 7, 2015

Study Start

March 12, 2015

Primary Completion

February 16, 2017

Study Completion

April 27, 2017

Last Updated

March 31, 2020

Results First Posted

July 24, 2018

Record last verified: 2020-03

Locations