Relapsing-Remitting Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, flushing, aspirin
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.
Interventions
DRUGdimethyl fumarate
DRUGacetylsalicylic acid
enteric-coated capsule
DRUGASA-Placebo
matched placebo
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Participant-reported flushing events during the first 4 weeks treatment, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score. |
| 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 | Participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
| Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS | Day 2 to Week 4 | Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score. |
| Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Day 1 to Week 4 | Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS | Day 1 to Week 12 | Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
| Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Day 1 to Week 12 | Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). For participants with more than 1 flushing event during a visit interval, the average duration for the visit interval was used. |
| Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48 | Week 13 to Week 48 | Participant-reported flushing events (which include redness, warmth, tingling, and/or itching of the skin) during Weeks 13 to 48 of treatment were recorded in the CRF. |
| 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 | AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. |
| Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Week 13 to Week 48 | AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. |
| Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Day 1 to Week 12 | A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin. |
| Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Week 13 to Week 48 | A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin. |
| 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 | Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
| 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) | Baseline, Week 24, Week 48 or ET | SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning). |
| 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 | Baseline, Week 24, Week 48 or ET | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Baseline, Week 24, Week 48 or ET | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Baseline, Week 24, Week 48 or ET | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Baseline, Week 24, Week 48 or ET | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Baseline, Week 24, Week 48 or ET | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement. |
| Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Baseline, Week 24, Week 48 or ET | For the EQ-VAS, the participant was instructed to draw a line on a 20-cm vertical scale at the point that best describes his or her own health, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. |
| 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) | Baseline, Week 24, Week 48 or early termination (ET) | SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning). |
| Percentage 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 | Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
| Worst 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 | Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
| Worst 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 | Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). |
Countries
Ireland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DMF + ASA-Placebo BID DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA was prohibited; between Weeks 9 and 48, ASA was allowed as needed.) | 81 |
| DMF + ASA 75 mg QAM DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 75 mg QAM and ASA-Placebo in the evening from Day 1 through Week 4. (Between Weeks 5 and 8, ASA was prohibited; between Weeks 9 and 48, ASA was allowed as needed.) | 80 |
| DMF + ASA 150 mg BID DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 150 mg BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA was prohibited; between Weeks 9 and 48, ASA was allowed as needed.) | 80 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 15 | 20 |
| Overall Study | Flushing event | 2 | 0 | 1 |
| Overall Study | Investigator Decision | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Other | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | DMF + ASA-Placebo BID | DMF + ASA 75 mg QAM | DMF + ASA 150 mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 40.17 years STANDARD_DEVIATION 10.63 | 39.48 years STANDARD_DEVIATION 8.48 | 40.16 years STANDARD_DEVIATION 8.23 | 39.94 years STANDARD_DEVIATION 9.15 |
| Gender Female | 59 Participants | 62 Participants | 60 Participants | 181 Participants |
| Gender Male | 22 Participants | 18 Participants | 20 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 77 / 81 | 76 / 80 | 76 / 80 |
| serious Total, serious adverse events | 4 / 81 | 8 / 80 | 5 / 80 |
Outcome results
Primary
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
Participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Day 1 to Week 4
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall tingling events | 81.3 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall warmth events | 92.5 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall flushing events | 91.3 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall redness events | 90.0 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall itching events | 87.5 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall warmth events | 97.4 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall flushing events | 96.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall redness events | 88.5 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall tingling events | 87.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall itching events | 79.5 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall itching events | 76.3 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall tingling events | 86.3 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall flushing events | 96.3 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall warmth events | 97.5 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS) | Overall redness events | 88.8 percentage of participants |
Comparison: Overall itching events95% CI: [-23.1, 0.6]
Comparison: Overall flushing events95% CI: [-2.6, 12.4]
Comparison: Overall flushing events95% CI: [-2.5, 12.5]
Comparison: Overall redness events95% CI: [-11.2, 8.1]
Comparison: Overall redness events95% CI: [-10.8, 8.3]
Comparison: Overall warmth events95% CI: [-1.8, 11.7]
Comparison: Overall warmth events95% CI: [-1.7, 11.7]
Comparison: Overall tingling events95% CI: [-5.4, 17.3]
Comparison: Overall tingling events95% CI: [-6.4, 16.4]
Comparison: Overall itching events95% CI: [-19.5, 3.5]
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)
Participant-reported flushing events during the first 4 weeks treatment, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.
Time frame: Day 2 to Week 4
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants evaluable at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 3; n=74, 74, 76 | 73.0 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 2; n=77, 76, 79 | 76.6 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Weeks 1-4 combined; n=80, 79, 80 | 90.0 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 1; n=80, 77, 80 | 83.8 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 4; n=72, 71, 71 | 59.7 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 2; n=77, 76, 79 | 61.8 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Weeks 1-4 combined; n=80, 79, 80 | 92.4 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 1; n=80, 77, 80 | 85.7 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 3; n=74, 74, 76 | 55.4 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 4; n=72, 71, 71 | 54.9 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 4; n=72, 71, 71 | 54.9 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 3; n=74, 74, 76 | 53.9 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Weeks 1-4 combined; n=80, 79, 80 | 88.8 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 2; n=77, 76, 79 | 69.6 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) | Week 1; n=80, 77, 80 | 83.8 percentage of participants |
Comparison: Weeks 1-4 combined95% CI: [-6.4, 11.2]
Comparison: Weeks 1-4 combined95% CI: [-10.8, 8.3]
Comparison: Week 195% CI: [-9.3, 13.2]
Comparison: Week 195% CI: [-11.4, 11.4]
Comparison: Week 295% CI: [-29.2, -0.3]
Comparison: Week 295% CI: [-20.9, 6.9]
Comparison: Week 395% CI: [-32.8, -2.4]
Comparison: Week 395% CI: [-34.1, -3.9]
Comparison: Week 495% CI: [-21, 11.4]
Comparison: Week 495% CI: [-21, 11.4]
Primary
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Day 1 to Week 4
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Tingling | 3.31 units on a scale | Standard Deviation 2.38 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Warmth | 5.03 units on a scale | Standard Deviation 2.54 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Overall flushing | 4.84 units on a scale | Standard Deviation 2.77 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Redness | 4.83 units on a scale | Standard Deviation 2.69 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Itching | 3.7 units on a scale | Standard Deviation 2.55 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Warmth | 4.88 units on a scale | Standard Deviation 2.38 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Overall flushing | 4.73 units on a scale | Standard Deviation 2.43 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Redness | 4.65 units on a scale | Standard Deviation 2.73 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Tingling | 3.62 units on a scale | Standard Deviation 2.53 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Itching | 3.64 units on a scale | Standard Deviation 2.76 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Itching | 3.23 units on a scale | Standard Deviation 2.66 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Tingling | 3.3 units on a scale | Standard Deviation 2.3 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Overall flushing | 4.78 units on a scale | Standard Deviation 2.53 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Warmth | 4.9 units on a scale | Standard Deviation 2.46 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS | Redness | 4.34 units on a scale | Standard Deviation 2.67 |
Primary
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.
Time frame: Day 2 to Week 4
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS | 4.36 units on a scale | Standard Deviation 2.66 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS | 3.99 units on a scale | Standard Deviation 2.63 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS | 3.93 units on a scale | Standard Deviation 2.47 |
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)
SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning).
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | 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) | Change at Week 24; n=68, 63, 61 | -0.139 units on a scale | Standard Deviation 11.66 |
| DMF + ASA-Placebo BID | 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) | Baseline; n=81, 80, 80 | 47.413 units on a scale | Standard Deviation 8.772 |
| DMF + ASA-Placebo BID | 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) | Change at Week 48/ET; n=68, 65, 64 | -0.976 units on a scale | Standard Deviation 13.759 |
| DMF + ASA 75 mg QAM | 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) | Change at Week 24; n=68, 63, 61 | -0.893 units on a scale | Standard Deviation 10.059 |
| DMF + ASA 75 mg QAM | 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) | Baseline; n=81, 80, 80 | 45.048 units on a scale | Standard Deviation 10.531 |
| DMF + ASA 75 mg QAM | 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) | Change at Week 48/ET; n=68, 65, 64 | -2.081 units on a scale | Standard Deviation 13.733 |
| DMF + ASA 150 mg BID | 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) | Baseline; n=81, 80, 80 | 46.496 units on a scale | Standard Deviation 10.812 |
| DMF + ASA 150 mg BID | 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) | Change at Week 48/ET; n=68, 65, 64 | -2.82 units on a scale | Standard Deviation 15.465 |
| DMF + ASA 150 mg BID | 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) | Change at Week 24; n=68, 63, 61 | -0.312 units on a scale | Standard Deviation 12.251 |
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)
SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning).
Time frame: Baseline, Week 24, Week 48 or early termination (ET)
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | 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) | Change at Week 24; n=68, 63, 61 | -0.014 units on a scale | Standard Deviation 9.154 |
| DMF + ASA-Placebo BID | 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) | Baseline; n=81, 80, 80 | 44.627 units on a scale | Standard Deviation 10.822 |
| DMF + ASA-Placebo BID | 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) | Change at Week 48/ET; n=68, 65, 64 | -1.008 units on a scale | Standard Deviation 10.31 |
| DMF + ASA 75 mg QAM | 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) | Change at Week 24; n=68, 63, 61 | 0.551 units on a scale | Standard Deviation 8.473 |
| DMF + ASA 75 mg QAM | 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) | Baseline; n=81, 80, 80 | 41.99 units on a scale | Standard Deviation 10.966 |
| DMF + ASA 75 mg QAM | 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) | Change at Week 48/ET; n=68, 65, 64 | -1.449 units on a scale | Standard Deviation 10.964 |
| DMF + ASA 150 mg BID | 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) | Baseline; n=81, 80, 80 | 43.16 units on a scale | Standard Deviation 11.438 |
| DMF + ASA 150 mg BID | 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) | Change at Week 48/ET; n=68, 65, 64 | -2.989 units on a scale | Standard Deviation 14.22 |
| DMF + ASA 150 mg BID | 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) | Change at Week 24; n=68, 63, 61 | -1.471 units on a scale | Standard Deviation 7.754 |
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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 48/ET; n=67, 63, 63 | 0.03 units on a scale | Standard Deviation 0.953 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 24; n=67, 63, 60 | -0.06 units on a scale | Standard Deviation 0.903 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Baseline; n=81, 79, 80 | 1.642 units on a scale | Standard Deviation 0.763 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 24; n=67, 63, 60 | -0.19 units on a scale | Standard Deviation 1.293 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Baseline; n=81, 79, 80 | 1.848 units on a scale | Standard Deviation 0.893 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 48/ET; n=67, 63, 63 | -0.127 units on a scale | Standard Deviation 1.184 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Baseline; n=81, 79, 80 | 1.763 units on a scale | Standard Deviation 0.917 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 48/ET; n=67, 63, 63 | -0.032 units on a scale | Standard Deviation 0.842 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression | Change at Week 24; n=67, 63, 60 | 0 units on a scale | Standard Deviation 0.803 |
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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 24; n=67, 63, 60 | -0.104 units on a scale | Standard Deviation 0.699 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Baseline; n=81, 79, 80 | 2 units on a scale | Standard Deviation 0.88 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 48/ET; n=67, 64, 63 | -0.09 units on a scale | Standard Deviation 0.712 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 24; n=67, 63, 60 | 0 units on a scale | Standard Deviation 1.032 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Baseline; n=81, 79, 80 | 2.038 units on a scale | Standard Deviation 0.869 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 48/ET; n=67, 64, 63 | 0.078 units on a scale | Standard Deviation 1.117 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Baseline; n=81, 79, 80 | 1.975 units on a scale | Standard Deviation 0.941 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 48/ET; n=67, 64, 63 | -0.127 units on a scale | Standard Deviation 0.707 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort | Change at Week 24; n=67, 63, 60 | 0.1 units on a scale | Standard Deviation 0.573 |
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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 24; n=67, 63, 60 | -0.045 units on a scale | Standard Deviation 0.442 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Baseline; n=81, 79, 80 | 1.321 units on a scale | Standard Deviation 0.668 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 48/ET; n=67, 64, 63 | -0.045 units on a scale | Standard Deviation 0.367 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 24; n=67, 63, 60 | -0.079 units on a scale | Standard Deviation 1.182 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Baseline; n=81, 79, 80 | 1.38 units on a scale | Standard Deviation 0.722 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 48/ET; n=67, 64, 63 | -0.109 units on a scale | Standard Deviation 1.143 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Baseline; n=81, 79, 80 | 1.363 units on a scale | Standard Deviation 0.621 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 48/ET; n=67, 64, 63 | 0.079 units on a scale | Standard Deviation 0.604 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care | Change at Week 24; n=67, 63, 60 | 0.017 units on a scale | Standard Deviation 0.567 |
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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 24; n=67, 63, 60 | -0.06 units on a scale | Standard Deviation 0.694 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Baseline; n=81, 79, 80 | 1.827 units on a scale | Standard Deviation 0.891 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 48/ET; n=67, 64, 63 | 0.149 units on a scale | Standard Deviation 0.783 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 24; n=67, 63, 60 | 0 units on a scale | Standard Deviation 1.244 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Baseline; n=81, 79, 80 | 1.975 units on a scale | Standard Deviation 0.947 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 48/ET; n=67, 64, 63 | -0.016 units on a scale | Standard Deviation 1.105 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Baseline; n=81, 79, 80 | 2.025 units on a scale | Standard Deviation 0.993 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 48/ET; n=67, 64, 63 | 0.063 units on a scale | Standard Deviation 0.896 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities | Change at Week 24; n=67, 63, 60 | -0.017 units on a scale | Standard Deviation 0.725 |
Secondary
Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS
For the EQ-VAS, the participant was instructed to draw a line on a 20-cm vertical scale at the point that best describes his or her own health, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 24; n=66, 63, 60 | -2.318 units on a scale | Standard Deviation 12.579 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Baseline; n=80, 80, 80 | 78.288 units on a scale | Standard Deviation 16.442 |
| DMF + ASA-Placebo BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 48/ET; n=66, 64, 63 | -3.061 units on a scale | Standard Deviation 18.053 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 24; n=66, 63, 60 | -0.587 units on a scale | Standard Deviation 17.24 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Baseline; n=80, 80, 80 | 69.6 units on a scale | Standard Deviation 19.535 |
| DMF + ASA 75 mg QAM | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 48/ET; n=66, 64, 63 | -0.438 units on a scale | Standard Deviation 17.834 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Baseline; n=80, 80, 80 | 73.438 units on a scale | Standard Deviation 16.38 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 48/ET; n=66, 64, 63 | -1.476 units on a scale | Standard Deviation 13.201 |
| DMF + ASA 150 mg BID | Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS | Change at Week 24; n=66, 63, 60 | -2.95 units on a scale | Standard Deviation 16.326 |
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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 24, Week 48 or ET
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | 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 | Change at Week 24; n=67, 63, 60 | -0.104 units on a scale | Standard Deviation 0.606 |
| DMF + ASA-Placebo BID | 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 | Baseline; n=81, 79, 80 | 1.877 units on a scale | Standard Deviation 0.967 |
| DMF + ASA-Placebo BID | 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 | Change at Week 48/ET; n=67, 63, 63 | 0.03 units on a scale | Standard Deviation 0.627 |
| DMF + ASA 75 mg QAM | 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 | Change at Week 24; n=67, 63, 60 | 0.095 units on a scale | Standard Deviation 1.214 |
| DMF + ASA 75 mg QAM | 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 | Baseline; n=81, 79, 80 | 1.785 units on a scale | Standard Deviation 0.887 |
| DMF + ASA 75 mg QAM | 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 | Change at Week 48/ET; n=67, 63, 63 | 0.079 units on a scale | Standard Deviation 1.021 |
| DMF + ASA 150 mg BID | 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 | Baseline; n=81, 79, 80 | 1.888 units on a scale | Standard Deviation 0.928 |
| DMF + ASA 150 mg BID | 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 | Change at Week 48/ET; n=67, 63, 63 | 0.095 units on a scale | Standard Deviation 0.56 |
| DMF + ASA 150 mg BID | 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 | Change at Week 24; n=67, 63, 60 | -0.05 units on a scale | Standard Deviation 0.467 |
Secondary
Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS
Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). For participants with more than 1 flushing event during a visit interval, the average duration for the visit interval was used.
Time frame: Day 1 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug). n=number of evaluable participants at given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 9-12 combined; n=45, 45, 51 | 0.66 hours | Standard Deviation 0.52 |
| DMF + ASA-Placebo BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 5-8 combined; n=57, 58, 59 | 1.06 hours | Standard Deviation 2.12 |
| DMF + ASA-Placebo BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 1-4 combined; n=73, 75, 77 | 0.69 hours | Standard Deviation 0.44 |
| DMF + ASA 75 mg QAM | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 5-8 combined; n=57, 58, 59 | 0.73 hours | Standard Deviation 0.52 |
| DMF + ASA 75 mg QAM | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 1-4 combined; n=73, 75, 77 | 0.8 hours | Standard Deviation 0.59 |
| DMF + ASA 75 mg QAM | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 9-12 combined; n=45, 45, 51 | 0.69 hours | Standard Deviation 0.59 |
| DMF + ASA 150 mg BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 1-4 combined; n=73, 75, 77 | 1.11 hours | Standard Deviation 1.16 |
| DMF + ASA 150 mg BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 9-12 combined; n=45, 45, 51 | 0.79 hours | Standard Deviation 0.94 |
| DMF + ASA 150 mg BID | Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS | Weeks 5-8 combined; n=57, 58, 59 | 1.08 hours | Standard Deviation 1.18 |
Comparison: Weeks 1-4 combined95% CI: [-0.414, 0.125]
Comparison: Weeks 1-4 combined95% CI: [-0.656, -0.128]
Comparison: Weeks 1-4 combined95% CI: [-0.507, 0.012]
Comparison: Weeks 5-8 combined95% CI: [-0.193, 0.945]
Comparison: Weeks 5-8 combined95% CI: [-0.498, 0.635]
Comparison: Weeks 5-8 combined95% CI: [-0.867, 0.251]
Comparison: Weeks 9-12 combined95% CI: [-0.308, 0.355]
Comparison: Weeks 9-12 combined95% CI: [-0.374, 0.254]
Comparison: Weeks 9-12 combined95% CI: [-0.4, 0.232]
Secondary
Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS
Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Day 1 to Week 12
Population: Although designated as a secondary endpoint, the duration of flushing events based on MGFSS could not be calculated because specific flushing events with start and end times was not captured in the MGFSS.
Secondary
Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks
A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin.
Time frame: Day 1 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing treatment | 0 participants |
| DMF + ASA-Placebo BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing study | 0 participants |
| DMF + ASA 75 mg QAM | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing treatment | 0 participants |
| DMF + ASA 75 mg QAM | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing study | 0 participants |
| DMF + ASA 150 mg BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing treatment | 2 participants |
| DMF + ASA 150 mg BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks | Discontinuing study | 2 participants |
Secondary
Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48
A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin.
Time frame: Week 13 to Week 48
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing treatment | 2 participants |
| DMF + ASA-Placebo BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing study | 2 participants |
| DMF + ASA 75 mg QAM | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing treatment | 0 participants |
| DMF + ASA 75 mg QAM | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing study | 0 participants |
| DMF + ASA 150 mg BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing treatment | 0 participants |
| DMF + ASA 150 mg BID | Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48 | Discontinuing study | 0 participants |
Secondary
Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug.
Time frame: Day 1 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Related event | 35 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued treatment due to event | 5 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued study due to event | 5 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Moderate or severe event | 24 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Serious event | 1 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Severe event | 3 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Any event | 66 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Serious event | 1 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Severe event | 5 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued treatment due to event | 9 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Any event | 68 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Moderate or severe event | 38 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued study due to event | 9 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Related event | 38 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued study due to event | 13 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Related event | 40 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Serious event | 2 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Any event | 63 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Moderate or severe event | 26 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Severe event | 8 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks | Discontinued treatment due to event | 12 participants |
Secondary
Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug.
Time frame: Week 13 to Week 48
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Moderate or severe event | 40 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Serious event | 3 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Related event | 45 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Any event | 66 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued study due to event | 9 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued treatment due to event | 9 participants |
| DMF + ASA-Placebo BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Severe event | 5 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Related event | 42 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Any event | 68 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Moderate or severe event | 50 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Severe event | 12 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Serious event | 7 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued treatment due to event | 6 participants |
| DMF + ASA 75 mg QAM | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued study due to event | 6 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Serious event | 3 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Moderate or severe event | 51 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued study due to event | 10 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Discontinued treatment due to event | 10 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Related event | 49 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Severe event | 12 participants |
| DMF + ASA 150 mg BID | Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48 | Any event | 66 participants |
Secondary
Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48
Participant-reported flushing events (which include redness, warmth, tingling, and/or itching of the skin) during Weeks 13 to 48 of treatment were recorded in the CRF.
Time frame: Week 13 to Week 48
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DMF + ASA-Placebo BID | Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48 | 36 participants |
| DMF + ASA 75 mg QAM | Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48 | 35 participants |
| DMF + ASA 150 mg BID | Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48 | 42 participants |
Secondary
Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS
Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Week 5 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 80.3 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 66.2 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 77.5 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 70.6 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 80.3 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 70.6 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 57.7 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 54.4 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 54.9 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 48.5 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 64.3 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 82.9 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 70.8 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 80.0 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 69.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 52.3 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 49.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 75.7 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 55.7 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 61.5 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 61.5 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 73.8 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 82.9 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 75.4 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 64.3 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 71.4 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 84.3 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 56.9 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 78.5 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 81.4 percentage of participants |
Comparison: Overall flushing, Weeks 5-8 combined95% CI: [-10.2, 15.4]
Comparison: Overall flushing, Weeks 5-8 combined95% CI: [-8.6, 16.6]
Comparison: Overall flushing, Weeks 9-12 combined95% CI: [-12.8, 18.9]
Comparison: Overall flushing, Weeks 9-12 combined95% CI: [-2.8, 27.3]
Comparison: Redness, Weeks 5-8 combined95% CI: [-15.7, 12.2]
Comparison: Redness, Weeks 5-8 combined95% CI: [-9.4, 17.3]
Comparison: Redness, Weeks 9-12 combined95% CI: [-25.1, 7]
Comparison: Redness, Weeks 9-12 combined95% CI: [-12, 18.5]
Comparison: Warmth, Weeks 5-8 combined95% CI: [-13.5, 12.9]
Comparison: Warmth, Weeks 5-8 combined95% CI: [-10.2, 15.4]
Comparison: Warmth, Weeks 9-12 combined95% CI: [-15.3, 15.7]
Comparison: Warmth, Weeks 9-12 combined95% CI: [-10.3, 19.9]
Comparison: Tingling, Weeks 5-8 combined95% CI: [-18.4, 14.3]
Comparison: Tingling, Weeks 5-8 combined95% CI: [-1.9, 29.3]
Comparison: Tingling, Weeks 9-12 combined95% CI: [-22.1, 11.8]
Comparison: Tingling, Weeks 9-12 combined95% CI: [-9.6, 23.9]
Comparison: Itching, Weeks 5-8 combined95% CI: [-6.8, 25.5]
Comparison: Itching, Weeks 5-895% CI: [-6.8, 25.5]
Comparison: Itching, Weeks 9-12 combined95% CI: [-13.2, 20.8]
Comparison: Itching, Weeks 9-12 combined95% CI: [-8.5, 25.3]
Secondary
Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Week 5 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug). n=number of evaluable participants at given time period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 74.6 percentage of participants |
| DMF + ASA-Placebo BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 9-12 combined; n=67, 62, 65 | 61.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 73.2 percentage of participants |
| DMF + ASA 75 mg QAM | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 9-12 combined; n=67, 62, 65 | 67.7 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 80.0 percentage of participants |
| DMF + ASA 150 mg BID | Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS | Weeks 9-12 combined; n=67, 62, 65 | 76.9 percentage of participants |
Comparison: Weeks 5-8 combined95% CI: [-15.8, 13]
Comparison: Weeks 5-8 combined95% CI: [-8.4, 19.1]
Comparison: Weeks 9-12 combined95% CI: [-9.9, 23]
Comparison: Weeks 9-12 combined95% CI: [0.2, 31.3]
Secondary
Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS
Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Week 5 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug). n=number of evaluable participants at given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 3.37 units on a scale | Standard Deviation 2.8 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 2.5 units on a scale | Standard Deviation 2.65 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 3.27 units on a scale | Standard Deviation 2.9 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 2.57 units on a scale | Standard Deviation 2.55 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 3.3 units on a scale | Standard Deviation 2.71 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 2.66 units on a scale | Standard Deviation 2.52 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 2.03 units on a scale | Standard Deviation 2.41 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 1.71 units on a scale | Standard Deviation 2.17 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 1.92 units on a scale | Standard Deviation 2.35 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 1.51 units on a scale | Standard Deviation 2.04 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 2.17 units on a scale | Standard Deviation 2.32 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 3.24 units on a scale | Standard Deviation 2.57 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 3.06 units on a scale | Standard Deviation 2.97 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 3.11 units on a scale | Standard Deviation 2.45 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 3.15 units on a scale | Standard Deviation 2.98 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 1.69 units on a scale | Standard Deviation 2.15 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 1.78 units on a scale | Standard Deviation 2.43 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 2.83 units on a scale | Standard Deviation 2.54 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 2.07 units on a scale | Standard Deviation 2.5 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 2.75 units on a scale | Standard Deviation 3.13 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 9-12 combined; n=68, 65, 65 | 2.54 units on a scale | Standard Deviation 2.69 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 9-12 combined; n=68, 65, 65 | 3.4 units on a scale | Standard Deviation 2.93 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 5-8 combined; n=71, 70, 70 | 3.49 units on a scale | Standard Deviation 2.54 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Warmth, Weeks 9-12 combined; n=68, 65, 65 | 3.45 units on a scale | Standard Deviation 2.85 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 5-8 combined; n=71, 70, 70 | 2.64 units on a scale | Standard Deviation 2.59 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Tingling, Weeks 5-8 combined; n=71, 70, 70 | 2.79 units on a scale | Standard Deviation 2.56 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 5-8 combined; n=71, 70, 70 | 3.57 units on a scale | Standard Deviation 2.45 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Itching, Weeks 9-12 combined; n=68, 65, 65 | 2.17 units on a scale | Standard Deviation 2.52 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Overall Flushing, Weeks 9-12 combined;n=68, 65, 65 | 3.45 units on a scale | Standard Deviation 2.74 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS | Redness, Weeks 5-8 combined; n=71, 70, 70 | 3.51 units on a scale | Standard Deviation 2.58 |
Secondary
Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS
Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Time frame: Week 5 to Week 12
Population: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug). n=number of evaluable participants at given time period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 3.00 units on a scale | Standard Deviation 2.61 |
| DMF + ASA-Placebo BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 9 to 12 combined; n=67, 62, 65 | 2.43 units on a scale | Standard Deviation 2.72 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 2.83 units on a scale | Standard Deviation 2.4 |
| DMF + ASA 75 mg QAM | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 9 to 12 combined; n=67, 62, 65 | 2.81 units on a scale | Standard Deviation 2.76 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 5-8 combined; n=71, 71, 70 | 3.47 units on a scale | Standard Deviation 2.64 |
| DMF + ASA 150 mg BID | Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS | Weeks 9 to 12 combined; n=67, 62, 65 | 2.95 units on a scale | Standard Deviation 2.5 |