Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Tr
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
What it found
Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.
What was tested
Treatment tested
- Dimethyl fumarate
Kelch-like ECH-associated protein 1 inhibitor
- Aspirin
Cyclooxygenase inhibitor
Placebo
- ASA-Placebo
Results by group
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Day 2 to Week 4
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| DMF + ASA-Placebo BID | 90.0 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 92.4 percentage of participants | 79 | |
| DMF + ASA 150 mg BID | 88.8 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 83.8 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 85.7 percentage of participants | 79 | |
| DMF + ASA 150 mg BID | 83.8 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 76.6 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 61.8 percentage of participants | 79 | |
| DMF + ASA 150 mg BID | 69.6 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 73.0 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 55.4 percentage of participants | 79 | |
| DMF + ASA 150 mg BID | 53.9 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 59.7 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 54.9 percentage of participants | 79 | |
| DMF + ASA 150 mg BID | 54.9 percentage of participants | 80 |
Difference in percentage 2.4 (95% CI -6.4–11.2)
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
Day 1 to Week 4
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| DMF + ASA-Placebo BID | 91.3 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 96.2 percentage of participants | 78 | |
| DMF + ASA 150 mg BID | 96.3 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 90.0 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 88.5 percentage of participants | 78 | |
| DMF + ASA 150 mg BID | 88.8 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 92.5 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 97.4 percentage of participants | 78 | |
| DMF + ASA 150 mg BID | 97.5 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 81.3 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 87.2 percentage of participants | 78 | |
| DMF + ASA 150 mg BID | 86.3 percentage of participants | 80 | |
| DMF + ASA-Placebo BID | 87.5 percentage of participants | 80 | |
| DMF + ASA 75 mg QAM | 79.5 percentage of participants | 78 | |
| DMF + ASA 150 mg BID | 76.3 percentage of participants | 80 |
Difference in percentage 4.9 (95% CI -2.6–12.4)
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
Day 2 to Week 4
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| DMF + ASA-Placebo BID | 4.36 units on a scale | 2.66 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 3.99 units on a scale | 2.63 (Standard Deviation) | 79 |
| DMF + ASA 150 mg BID | 3.93 units on a scale | 2.47 (Standard Deviation) | 80 |
DMF + ASA-Placebo BID
DMF + ASA 75 mg QAM
DMF + ASA 150 mg BID
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
Day 1 to Week 4
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| DMF + ASA-Placebo BID | 4.84 units on a scale | 2.77 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 4.73 units on a scale | 2.43 (Standard Deviation) | 78 |
| DMF + ASA 150 mg BID | 4.78 units on a scale | 2.53 (Standard Deviation) | 80 |
| DMF + ASA-Placebo BID | 4.83 units on a scale | 2.69 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 4.65 units on a scale | 2.73 (Standard Deviation) | 78 |
| DMF + ASA 150 mg BID | 4.34 units on a scale | 2.67 (Standard Deviation) | 80 |
| DMF + ASA-Placebo BID | 5.03 units on a scale | 2.54 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 4.88 units on a scale | 2.38 (Standard Deviation) | 78 |
| DMF + ASA 150 mg BID | 4.9 units on a scale | 2.46 (Standard Deviation) | 80 |
| DMF + ASA-Placebo BID | 3.31 units on a scale | 2.38 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 3.62 units on a scale | 2.53 (Standard Deviation) | 78 |
| DMF + ASA 150 mg BID | 3.3 units on a scale | 2.3 (Standard Deviation) | 80 |
| DMF + ASA-Placebo BID | 3.7 units on a scale | 2.55 (Standard Deviation) | 80 |
| DMF + ASA 75 mg QAM | 3.64 units on a scale | 2.76 (Standard Deviation) | 78 |
| DMF + ASA 150 mg BID | 3.23 units on a scale | 2.66 (Standard Deviation) | 80 |
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| DMF + ASA-Placebo BID | 81 | 4 (4.9%) | |
| DMF + ASA 75 mg QAM | 80 | 8 (10.0%) | |
| DMF + ASA 150 mg BID | 80 | 5 (6.3%) |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Day 2 to Week 4
SafetyPercentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
Day 1 to Week 4
SafetyWorst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
Day 2 to Week 4
SafetyWorst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
Day 1 to Week 4
SafetyThe primary endpoints are as follows:
Other measures (20)
Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
Week 5 to Week 12
SafetyPercentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS
Week 5 to Week 12
SafetyWorst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS
Week 5 to Week 12
SafetyWorst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS
Week 5 to Week 12
SafetyDuration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS
Day 1 to Week 12
SafetyDuration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS
Day 1 to Week 12
SafetyNumber of Participants With Self-Reported Flushing Events During Weeks 13 to 48
Week 13 to Week 48
Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks
Day 1 to Week 12
SafetyNumber of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
Week 13 to Week 48
SafetyNumber of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks
Day 1 to Week 12
Who could take part
Relapsing MS · 18 and over
Show the full criteria
Inclusion 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
Exclusion criteria
Not separately supplied in the registry.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Loading reviews and guidelines…
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History
Started
May 2014
Main results due
Feb 2015
Finished
Nov 2015
Results posted
Dec 2016