Phase 4
Completed N=241
Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Treated Participants With Relapsing-Remitting Multiple Sclerosis
Source: ClinicalTrials.gov NCT02090413 ↗Enrolled (actual)
241
Serious AEs
7.0%
Results posted
Dec 2016
Primary outcomePrimary: Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) — 90.0; 92.4; 88.8; 83.8 percentage of participants
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) |
90.0; 92.4; 88.8; 83.8; 85.7; 83.8 | — |
| PRIMARY Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) |
91.3; 96.2; 96.3; 90.0; 88.5; 88.8 | — |
| PRIMARY Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS |
4.36; 3.99; 3.93 | — |
| PRIMARY Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS |
4.84; 4.73; 4.78; 4.83; 4.65; 4.34 | — |
| SECONDARY Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS |
74.6; 73.2; 80.0; 61.2; 67.7; 76.9 | — |
| SECONDARY Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS |
80.3; 82.9; 84.3; 66.2; 69.2; 78.5 | — |
| SECONDARY Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS |
3.00; 2.83; 3.47; 2.43; 2.81; 2.95 | — |
| SECONDARY Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS |
3.37; 3.24; 3.57; 2.5; 3.15; 3.45 | — |
| SECONDARY Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS |
— | — |
| SECONDARY Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS |
0.69; 0.8; 1.11; 1.06; 0.73; 1.08 | — |
| SECONDARY Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48 |
36; 35; 42 | — |
| SECONDARY Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks |
66; 68; 63; 24; 38; 26 | — |
| SECONDARY Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 |
66; 68; 66; 40; 50; 51 | — |
| SECONDARY Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks |
0; 0; 2; 0; 0; 2 | — |
| SECONDARY Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 |
2; 0; 0; 2; 0; 0 | — |
| SECONDARY 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) |
44.627; 41.99; 43.16; -0.014; 0.551; -1.471 | — |
| SECONDARY 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) |
47.413; 45.048; 46.496; -0.139; -0.893; -0.312 | — |
| SECONDARY 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 |
1.877; 1.785; 1.888; -0.104; 0.095; -0.05 | — |
| SECONDARY Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care |
1.321; 1.38; 1.363; -0.045; -0.079; 0.017 | — |
| SECONDARY Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities |
1.827; 1.975; 2.025; -0.06; 0; -0.017 | — |
| SECONDARY Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort |
2; 2.038; 1.975; -0.104; 0; 0.1 | — |
| SECONDARY Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression |
1.642; 1.848; 1.763; -0.06; -0.19; 0 | — |
| SECONDARY Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS |
78.288; 69.6; 73.438; -2.318; -0.587; -2.95 | — |
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
Data sourced from ClinicalTrials.gov (NCT02090413). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.