Phase 4 Study of Effect of Aspirin on Flushing in Dimethy... | NCT02090413

ID	Type	Description	Link
2013-001895-40	EudraCT Number

Label	Type	Description	Intervention Names
DMF + ASA 150 mg BID	Experimental	DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 150 mg is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)	Drug: dimethyl fumarate Drug: acetylsalicylic acid
DMF + ASA 75 mg QAM	Experimental	DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 75 mg is taken in the morning (QAM) and ASA-Placebo is taken in the evening (QPM) from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)	Drug: dimethyl fumarate Drug: acetylsalicylic acid Drug: ASA-Placebo
DMF + ASA-Placebo BID	Experimental	DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)	Drug: dimethyl fumarate Drug: ASA-Placebo

Name	Type	Description	Arm Group Labels	Other Names
dimethyl fumarate	Drug		DMF + ASA 150 mg BID DMF + ASA 75 mg QAM DMF + ASA-Placebo BID	BG00012

Measure	Description	Time Frame
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.	Day 2 to Week 4
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).	Day 1 to Week 4
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.	Day 2 to Week 4
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS

Measure	Description	Time Frame
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).

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Cork			Ireland
Research Site

ID	Title	Description
FG000	DMF + ASA-Placebo BID	Dimethyl fumarate (DMF) 120 mg taken twice daily (BID) for the first 7 days and 240 mg BID from Week 2 through Week 48. Acetylsalicylic acid (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.)
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Number

percentage of participants

Day 2 to Week 4

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)
OG002	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.)

Units	Counts
Participants	OG00080 OG00179 OG00280

Title

Denominators

Categories

Weeks 1-4 combined; n=80, 79, 80

Title	Measurements
	OG00090.0 OG00192.4 OG00288.8

Week 1; n=80, 77, 80

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Weeks 1-4 combined					Difference in percentage	2.4			2-Sided	95	-6.4	11.2			Two sided 95% CI of difference in proportions was constructed based on the normal approximation to the binomial distribution.	No	Superiority or Other
OG000 OG002

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).

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

percentage of participants

Day 1 to Week 4

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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.

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Mean

Standard Deviation

units on a scale

Day 2 to Week 4

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)
OG002

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).

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Mean

Standard Deviation

units on a scale

Day 1 to Week 4

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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).

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.

Posted

Number

percentage of participants

Week 5 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)
OG002

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).

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

percentage of participants

Week 5 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)

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).

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.

Posted

Mean

Standard Deviation

units on a scale

Week 5 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)
OG002

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).

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.

Posted

Mean

Standard Deviation

units on a scale

Week 5 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)

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).

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.

Posted

Day 1 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)
OG002	DMF + ASA 150 mg BID

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.

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.

Posted

Mean

Standard Deviation

hours

Day 1 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)

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.

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

participants

Week 13 to Week 48

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)
OG002	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.)

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.

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

participants

Day 1 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)

Secondary

Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

participants

Week 13 to Week 48

ID	Title	Description
OG000	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.)
OG001	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.)

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.

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

participants

Day 1 to Week 12

ID	Title	Description
OG000	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.)
OG001	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.)
OG002	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.)

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.

Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Posted

Number

participants

Week 13 to Week 48

ID	Title	Description
OG000	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.)
OG001	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.)
OG002	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.)

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).

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or early termination (ET)

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	DMF + ASA 75 mg QAM

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).

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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.

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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.

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)

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."

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, Week 48 or ET

ID	Title	Description
OG000	DMF + ASA-Placebo BID	DMF 120 mg BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo 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.)
OG001	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.)
OG002	DMF + ASA 150 mg BID

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00017 affected81 at risk EG00121 affected80 at risk EG00219 affected80 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00012 affected81 at risk EG00116 affected80 at risk EG00223 affected80 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected81 at risk EG00114 affected80 at risk EG00214 affected80 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected81 at risk EG0015 affected80 at risk EG00210 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected81 at risk EG00110 affected80 at risk EG0027 affected80 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0017 affected80 at risk EG0025 affected80 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected81 at risk EG0010 affected80 at risk EG0025 affected80 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0013 affected80 at risk EG0024 affected80 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0011 affected80 at risk EG0022 affected80 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0013 affected80 at risk EG0024 affected80 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0022 affected80 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Eructation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Flatulence	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Abdominal mass	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Faeces soft	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Toothache	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0022 affected80 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00020 affected81 at risk EG00115 affected80 at risk EG00216 affected80 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0008 affected81 at risk EG0019 affected80 at risk EG00210 affected80 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG00110 affected80 at risk EG0027 affected80 at risk
Sinusitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0025 affected80 at risk
Candida infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0013 affected80 at risk EG0022 affected80 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0022 affected80 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0013 affected80 at risk EG0022 affected80 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0024 affected80 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Oral herpes	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0013 affected80 at risk EG0020 affected80 at risk
Tooth infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Gastric infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0022 affected80 at risk
Ear infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Herpes zoster	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Infected dermal cyst	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Kidney infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Laryngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Eye infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Viral pharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected81 at risk EG00114 affected80 at risk EG00218 affected80 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG00112 affected80 at risk EG0025 affected80 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG0017 affected80 at risk EG0025 affected80 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected81 at risk EG0018 affected80 at risk EG0024 affected80 at risk
Migraine	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Balance disorder	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0023 affected80 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0012 affected80 at risk EG0024 affected80 at risk
Amnesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Memory impairment	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Dysgeusia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Dystonia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Optic neuritis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0023 affected80 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Tremor	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Uhthoff's phenomenon	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Visual field defect	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected81 at risk EG0014 affected80 at risk EG0022 affected80 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG0012 affected80 at risk EG0027 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0016 affected80 at risk EG0023 affected80 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0023 affected80 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0023 affected80 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG00111 affected80 at risk EG0024 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0024 affected80 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0011 affected80 at risk EG0022 affected80 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0022 affected80 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Xanthelasma	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected81 at risk EG0013 affected80 at risk EG0025 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0013 affected80 at risk EG0022 affected80 at risk
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0012 affected80 at risk EG0023 affected80 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0014 affected80 at risk EG0026 affected80 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected81 at risk EG00111 affected80 at risk EG0027 affected80 at risk
Influenza like illness	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0024 affected80 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0022 affected80 at risk
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0022 affected80 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0022 affected80 at risk
Feeling abnormal	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Malaise	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0022 affected80 at risk
Depressed mood	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0013 affected80 at risk EG0022 affected80 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Irritability	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Anger	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Libido decreased	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Mental disorder	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Sleep disorder	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected81 at risk EG0010 affected80 at risk EG0022 affected80 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Breast cyst	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Breast mass	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Vulvovaginal pain	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG0012 affected80 at risk EG0026 affected80 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0013 affected80 at risk EG0021 affected80 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Vaccination complication	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Vision blurred	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0022 affected80 at risk
Ocular hyperaemia	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Eye irritation	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Alanine aminotransferase abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0023 affected80 at risk
Aspartate aminotransferase abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Liver function test abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0012 affected80 at risk EG0021 affected80 at risk
Serum ferritin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Smear cervix abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Weight increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Flushing	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG00042 affected81 at risk EG00136 affected80 at risk EG00245 affected80 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Peripheral coldness	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Hearing impaired	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Palpitations	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Gout	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Fecal incontinence	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Anorectal discomfort	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Gingival swelling	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Stomach ulcer	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Hot flush	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Impetigo	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Oral candidiasis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Tonsillitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0022 affected80 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Gingivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Herpes simplex	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Infected cyst	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Labyrinthitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Lyme disease	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Periodontitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Pyuria	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Rhinitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Skin infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Tooth abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Sensory disturbance	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Neuralgia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0012 affected80 at risk EG0020 affected80 at risk
Aphasia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Aphonia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Coordination abnormal	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Dysarthria	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Hemiparesis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Hyperaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Lethargy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Motor dysfunction	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Nerve compression	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Pain	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Peroneal nerve palsy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Somnolence	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected81 at risk EG0018 affected80 at risk EG0023 affected80 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Mastication disorder	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Throat tightness	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Nail hypertrophy	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Pruritis generalised	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Rosacea	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Lymphocyte count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0005 affected81 at risk EG0015 affected80 at risk EG0025 affected80 at risk
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Blood iron decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Lymphocyte count abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Blood folate decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Haemoglobin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Neutrophil count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Vitamin B12 decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
White blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
White blood cells urine positive	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Sunburn	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Panic attack	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Gait disturbance	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0023 affected80 at risk
Adverse drug reaction	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Device failure	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Feeling hot	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Eye pain	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Colour blindness acquired	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Diplopia	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Scleritis	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Anisomastia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Menstruation irregular	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Nipple pain	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Pruritus genital	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Testicular cyst	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Testicular pain	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Food allergy	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0021 affected80 at risk
Seasonal allergy	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Dysuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Renal pain	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Cow's milk intolerance	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected81 at risk EG0010 affected80 at risk EG0020 affected80 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Burning sensation	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0010 affected80 at risk EG0021 affected80 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Disturbance in attention	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0020 affected80 at risk
Viral infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected81 at risk EG0011 affected80 at risk EG0023 affected80 at risk

ID	Term
D020529	Multiple Sclerosis, Relapsing-Remitting
D009103	Multiple Sclerosis
D005483	Flushing

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases
D012877	Skin Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D005650	Fumarates
D003998	Dicarboxylic Acids
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D012459	Salicylates
D062385	Hydroxybenzoates
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons

ID	Title	Description
BG000	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.)
BG001	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.)
BG002	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.)
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.)	4	81	77	81
EG001	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.)	8	80	76	80
EG002	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.)	5	80	76	80