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

Multiple Sclerosis Clinical Trial

— MITIGATE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02410278
• Other study ID #: 109MS414
• Status: Completed
• Phase: Phase 4
• Start date: March 12, 2015
• Est. completion date: April 27, 2017

Study information

• Verified date: March 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: April 27, 2017
• Est. primary completion date: February 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• dimethyl fumarate
Starting dose of 120 mg twice daily orally After 7 days, maintenance dose of 240 mg twice daily orally
• montelukast
As described in the treatment arm
• Placebo
Matched placebo

Locations

Country	Name	City	State
United States	Research Site	Alexandria	Virginia
United States	Research Site	Amherst	New York
United States	Research Site	Aurora	Colorado
United States	Research Site	Carmichael	California
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Chicago	Illinois
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Dayton	Ohio
United States	Research Site	Dickson City	Pennsylvania
United States	Research Site	Fairfield	Connecticut
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Flossmoor	Illinois
United States	Research Site	Freehold	New Jersey
United States	Research Site	Greensburg	Pennsylvania
United States	Research Site	Hendersonville	North Carolina
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	Kansas City	Missouri
United States	Research Site	La Jolla	California
United States	Research Site	La Mesa	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Naples	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Newport News	Virginia
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Patchogue	New York
United States	Research Site	Pomona	California
United States	Research Site	Portland	Oregon
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rome	Georgia
United States	Research Site	Round Rock	Texas
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Sanford	North Carolina
United States	Research Site	Scarborough	Maine
United States	Research Site	Seattle	Washington
United States	Research Site	Simi Valley	California
United States	Research Site	Smyrna	Georgia
United States	Research Site	Sunrise	Florida
United States	Research Site	Tualatin	Oregon
United States	Research Site	Uniontown	Ohio
United States	Research Site	Washington	District of Columbia
United States	Research Site	Wilkes-Barre	Pennsylvania
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Average Change From Baseline in GSRS Overall Score at Day 1 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). 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)
Secondary	Average Change From Baseline in GSRS Overall Score at Day 1 to Week 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). 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)
Secondary	Time to First Worsening From Baseline in GSRS Overall Score at Day 1 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). 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)
Secondary	Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8	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)
Secondary	Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8	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)
Secondary	Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment	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)
Secondary	Percentage of Participants Who Required GI Symptomatic Therapy During the Study	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
Secondary	Percentage of Participants Who Discontinued DMF Therapy Due to GI-Related Adverse Events (AEs) From 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
Secondary	Percentage of Participants Who Experienced AEs Related to Flushing	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