Clinical trial NCT02090413: Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Treated Participants With Relapsing-Remitting Multiple Sclerosis
Official title: A Phase 4, Randomized, Double-Blind Study With a Safety Extension Period to Evaluate the Effect of Aspirin on Flushing Events in Subjects With Relapsing-Remitting Multiple Sclerosis Treated With Tecfidera® (Dimethyl Fumarate) Delayed-Release Capsules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: multiple sclerosis
flushing
aspirin
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2014-03-18
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate whether 150 mg enteric-coated aspirin (acetylsalicylic acid \[ASA\]) taken twice a day (BID) with dimethyl fumarate (DMF) administration or 75 mg enteric-coated ASA taken once daily in the morning (QAM) with DMF administration reduces the incidence and/or severity of flushing events in subjects with relapsing-remitting multiple sclerosis (RRMS) compared with ASA-placebo administered with DMF in the clinical practice setting.

Secondary objectives of this study are: to evaluate the safety and tolerability of DMF administered with and without enteric-coated ASA in the clinical practice setting; to evaluate the impact of DMF administration on quality of life as measured by the Short Form 36 (SF-36®) and European Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L) questionnaires.


Eligibility criteria: Key Inclusion Criteria:

* Naïve to fumaric acid esters (e.g. DMF, Fumaderm, compounded fumarates)
* Diagnosed with RRMS and satisfies the approved therapeutic indication for DMF
* Participants of childbearing potential must practice effective contraception and be willing and able to continue contraception throughout the study
* Ability to complete the tolerability scales accurately using the electronic diary (eDiary) and ability to complete the paper Flushing Diaries

Key Exclusion Criteria:

* Inability or unwillingness to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation
* One or more major comorbidities that, in the opinion of the Investigator, may affect the outcome of the study or otherwise makes the subject an unsuitable candidate for study participation. The prevailing product labels for both DMF and ASA should be used as guides
* Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible)
* Chronic use (≥7 consecutive days) of ASA- or nonsteroidal anti-inflammatory drugs (NSAID)-containing products within the month prior to enrollment in the study
* A known intolerance to ASA
* Active peptic ulceration or a history of peptic ulceration, hemophilia or other clotting disorders, or gout
* Known hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) in response to ASA or NSAID administration
* Impaired hepatic or renal function, in the opinion of the investigator
* Female subject is pregnant, lactating, or will be attempting to become pregnant during the Double-Blind Period (first 12 weeks) of the study
* Currently participating in another interventional clinical trial

NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
timeFrame: Day 2 to Week 4
measure: Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
timeFrame: Day 1 to Week 4
measure: Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
timeFrame: Day 2 to Week 4
measure: Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
timeFrame: Day 1 to Week 4
Secondary outcomes:
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
timeFrame: Week 5 to Week 12
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS
timeFrame: Week 5 to Week 12
measure: Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS
timeFrame: Week 5 to Week 12
measure: Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS
timeFrame: Week 5 to Week 12
measure: Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS
timeFrame: Day 1 to Week 12
measure: Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS
timeFrame: Day 1 to Week 12
measure: Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48
timeFrame: Week 13 to Week 48
measure: Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks
timeFrame: Day 1 to Week 12
measure: Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
timeFrame: Week 13 to Week 48
measure: Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks
timeFrame: Day 1 to Week 12
measure: Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48
timeFrame: Week 13 to Week 48
measure: Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Physical Component Summary (PCS)
timeFrame: Baseline, Week 24, Week 48 or early termination (ET)
measure: Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Mental Component Summary (MCS)
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) Questionnaire: Mobility
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression
timeFrame: Baseline, Week 24, Week 48 or ET
measure: Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS
timeFrame: Baseline, Week 24, Week 48 or ET
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Basingstoke
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: