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Tecfidera Slow-Titration Study (TITRATION)

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ClinicalTrials.gov Identifier: NCT02428231
Recruitment Status : Terminated (Sponsor decision)
First Posted : April 28, 2015
Results First Posted : May 5, 2017
Last Update Posted : May 5, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
The primary objective of the study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the incidence of dimethyl fumarate (DMF [Tecfidera])-related gastrointestinal (GI) adverse events (AEs) in participants with multiple sclerosis (MS). The secondary objective of this study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the average severity and duration of GI symptoms over 12 weeks of DMF treatment in this study population.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: dimethyl fumarate Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Treatment-Blind Phase 3b Study to Evaluate Whether 6-Week Up-Titration in Tecfidera® Dose is Effective in Reducing the Incidence of Gastrointestinal Adverse Events in Patients With Multiple Sclerosis
Study Start Date : April 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Standard Treatment (One-Week Titration)
120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks
Drug: dimethyl fumarate
Participants will be dosed twice daily for 12 weeks.
Other Names:
  • DMF
  • Tecfidera
  • BG00012

Experimental: Slow Up-Titration (Six-Week Titration)
120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF twice daily for 6 weeks
Drug: dimethyl fumarate
Participants will be dosed twice daily for 12 weeks.
Other Names:
  • DMF
  • Tecfidera
  • BG00012




Primary Outcome Measures :
  1. Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS) [ Time Frame: from Week 2 (Baseline) to Week 14 ]
    The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.


Secondary Outcome Measures :
  1. Average Change From Baseline in GSRS Scores During DMF Treatment [ Time Frame: Week 2 (Baseline), Week 14 ]
    Average change from baseline in GSRS scores over the 12 weeks of DMF treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.

  2. Time to First Worsening From Baseline in GSRS Score [ Time Frame: Week 2 (Baseline), Week 14 ]
    The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.

  3. Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score [ Time Frame: Week 2 (Baseline), Week 14 ]
    The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.

  4. Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 14 [ Time Frame: Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14 ]
    Average change from baseline to end of DMF treatment in the GSRS. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Diagnosis of MS consistent with locally labeled indication for DMF
  • No prior treatment with DMF
  • Female subjects of childbearing potential who are not surgically sterile and male subjects must practice effective contraception during their participation in the study
  • Have had a recent complete blood count (CBC), including lymphocyte count, that does not preclude participation in the study, in the judgement of the investigator

Key Exclusion Criteria:

  • Have a recent history or ongoing GI illness (e.g., peptic ulcer, irritable bowel syndrome) or any other current condition with GI signs and symptoms (e.g., nausea, vomiting, abdominal pain, or diarrhea) that may interfere with assessment of study endpoints
  • Have other major comorbid conditions that preclude participation in the study, as determined by the investigator
  • Participant is pregnant, breastfeeding, or planning a pregnancy during the study period
  • Are receiving concomitant disease-modifying therapies for MS including, but not limited to, natalizumab, interferon beta, glatiramer acetate, fingolimod, alemtuzumab, teriflunomide, or laquinimod at screening
  • History of severe allergic or anaphylactic reactions or known drug hypersensitivity
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02428231


Locations
United States, Arizona
Research Site
Gilbert, Arizona, United States
Research Site
Phoenix, Arizona, United States
United States, California
Research Site
Long Beach, California, United States
United States, Florida
Research Site
Miami, Florida, United States
United States, Indiana
Research Site
Avon, Indiana, United States
Research Site
Franklin, Indiana, United States
United States, Kansas
Research Site
Overland Park, Kansas, United States
United States, Maine
Research Site
Lewiston, Maine, United States
United States, North Carolina
Research Site
Asheville, North Carolina, United States
Research Site
Cary, North Carolina, United States
Research Site
Charlotte, North Carolina, United States
Research Site
Wilmington, North Carolina, United States
United States, Ohio
Research Site
Cincinnati, Ohio, United States
United States, Texas
Research Site
Dallas, Texas, United States
United States, Washington
Research Site
Wenatchee, Washington, United States
Belgium
Research Site
Leuven, Belgium
Research Site
Wilrijk, Belgium
Czech Republic
Research Site
Prague, Czech Republic
Italy
Research Site
Merano, Bolzano, Italy
Research Site
Montichiari, Italy
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02428231     History of Changes
Other Study ID Numbers: 109MS416
2014-004562-22 ( EudraCT Number )
First Posted: April 28, 2015    Key Record Dates
Results First Posted: May 5, 2017
Last Update Posted: May 5, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Dimethyl Fumarate
Dermatologic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs