HealthyPhase 3NCT01568112

Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl Fumarate

A Phase 3 study testing BG00012 (dimethyl fumarate) and ASA in people with Healthy, run by Biogen at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 25 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: BG00012 (dimethyl fumarate) and ASA
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 173 participants
Where: 1 siteUnited States
Study dates: Apr 2012to Oct 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Must give written informed consent and any authorizations required by local law
Must have a body mass index (BMI) of between 18.0 to 34.0 kg/m^2,inclusive.
Ability to complete the tolerability scales by accurately using the hand-held subject reporting device
Subjects of childbearing potential must be willing to practice effective contraception

Who cannot join

History of clinically significant diseases
History of severe allergic or anaphylactic reactions
Intolerance to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
Diarrhea, constipation, abdominal pain, flushing or nausea within 28 days prior to Day 1
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Saint Paul, Minnesota

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Phase 3b Study to Evaluate Effects of Aspirin or Dose Titration on Flushing and Gastrointestinal Events Following Oral Administration of BG00012 Dosed at 240 mg BID

The primary objective of the study is to evaluate whether premedication with 325 mg microcoated aspirin (ASA) tablet or a slow-titration dosing schedule of BG00012 reduces the incidence and severity of flushing and GI events following oral administration of BG00012 dosed at 240 mg twice a day (BID) in healthy volunteers. The secondary objective of this study is to evaluate the safety and tolerability of BG00012 when administered orally as a 240 mg BID dose regimen with and without 325 mg ASA premedication or following a slow-titration dosing schedule in healthy volunteers.

Conditions: Healthy
Being tested: BG00012 (dimethyl fumarate), BG00012 placebo, ASA, ASA placebo
Keywords: BG00012, gastrointestinal events, flushing events, dose titration, pre-medication, aspirin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BG00012 (dimethyl fumarate)Drug
Also called BG-12, oral fumarate, DMF
Each capsule contains 120 mg dimethyl fumarate (DMF). Fast titration involves taking one 120 mg capsule in the morning and one in the evening (240 mg daily) for one week, and then escalating to a dose of 480 mg daily (two capsules morning and evening) for the remainder of the study.Slow titration expands the dose escalation time to 4 weeks.
BG00012 placeboDrug
Placebo matching BG00012
ASADrug
Also called acetylsalicylic acid, aspirin
325 mg microcoated aspirin (ASA)
ASA placeboDrug
Placebo matching aspirin

Study groups in NCT01568112
Study group	Role	What they receive
BG00012	Experimental	Participants received BG00012 for 8 weeks (120 mg BID during the first week and 240 mg BID during the subsequent 7 weeks) and premedication with ASA placebo during the first 4 weeks. Receives: Drug: BG00012 (dimethyl fumarate); Drug: BG00012 placebo; Drug: ASA placebo
Placebo	Placebo comparator	Participants received BG00012 placebo for 8 weeks and premedication with ASA placebo during the first 4 weeks. Receives: Drug: BG00012 placebo; Drug: ASA placebo
BG00012 + ASA	Experimental	Participants received BG00012 for 8 weeks (120 mg BID during the first week and 240 mg BID during the subsequent 7 weeks) and premedication with ASA during the first 4 weeks. Receives: Drug: BG00012 (dimethyl fumarate); Drug: BG00012 placebo; Drug: ASA
BG00012 Slow Titration	Experimental	Participants received BG00012 for 8 weeks (120 mg once daily [QD] during Week 1, 120 mg BID during Week 2, 240 mg AM/120mg PM during Week 3, and 240 mg BID during Week 4, and 240 mg BID during Weeks 5 to 8) and premedication with ASA placebo during the first 4 weeks. Receives: Drug: BG00012 (dimethyl fumarate); Drug: BG00012 placebo; Drug: ASA placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)
Participant-reported flushing side effect events during the treatment period 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).
Measured: Day 1 to Week 8
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS
Participant-reported flushing side effect events during Weeks 1 to 4 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).
Measured: Week 1 to Week 4
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS
Participant-reported flushing side effect events during Weeks 1 to 4 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).
Measured: Week 5 to Week 8
Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS
Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, 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).
Measured: Day 1 to Week 4
Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS
Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, 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).
Measured: Week 5 to Week 8
Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Participant-reported flushing events during the overall treatment period, 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 events reported in the 24 hours after the first dose on Day 1.
Measured: Day 2 to Week 8
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS
Participant-reported flushing events during Weeks 1 to 4 of treatment (combined), 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 events reported in the 24 hours after the first dose on Day 1.
Measured: Day 2 to Week 4
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS
Participant-reported flushing events during Weeks 5 to 8 of treatment (combined), 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.
Measured: Week 5 to Week 8
Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Measured: Day 1 to Week 8
Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Measured: Day 1 to Week 4
Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Measured: Week 5 to Week 8
Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.
Measured: Day 1 to Week 4
Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.
Measured: Week 5 to Week 8
Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.
Measured: Day 1 to Week 8
Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.
Measured: Week 1 to Week 4
Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.
Measured: Week 5 to Week 8

Secondary outcomes (12)

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)
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 subject at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes. An AE was considered treatment-emergent if it occurred after the start of study treatment or was present prior to the start of study treatment but subsequently worsened.
Measured: Day 1 up to end of Safety Follow-up (9 weeks)
Clinical Laboratory Shifts From Baseline in Reported Values: Hematology
Number of participants with clinical laboratory shifts from baseline in hematology values. Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. abs=absolute
Measured: Day 1 to Week 8
Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
Number of participants with clinical laboratory shifts from baseline in blood chemistry values. Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. ALP=alkaline phosphatase, ALT=alanine aminotransferase, AST=aspartate aminotransferase, GGT=gamma-glutamyl transferase, LDH=lactate dehydrogenase, BUN=blood urea nitrogen.
Measured: Day 1 to Week 8
Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis
Number of participants with clinical laboratory shifts from baseline in urinalysis values.Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. Shift to positive includes negative to positive and unknown to positive. RBC=red blood cells, WBC=white blood cells.
Measured: Day 1 to Week 8
Number of Participants With Abnormalities in Vital Signs
↑=increase; ↓=decrease; BL=baseline; bpm=beats per minute; SBP=systolic blood pressure; DBP=diastolic blood pressure; b/m=breaths per minute
Measured: Day 1 to Week 8
Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
Shift to 'abnormal, not adverse event' includes unknown or normal to 'abnormal, not adverse event.' Shift to 'abnormal, adverse event' includes unknown or normal to 'abnormal, adverse event.'
Measured: Day 1 to Week 8
Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes.
Measured: Day 1 to Week 8
Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS
For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes.
Measured: Week 1 to Week 4
Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS
For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes.
Measured: Week 5 to Week 8
Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS
Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects.
Measured: Day 1 to Week 8
Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS
Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects.
Measured: Week 1 to Week 4
Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS
Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects.
Measured: Week 5 to Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2012Oct 2012

First posted2 Apr 2012 (estimated)
Study startApr 2012
Primary completionOct 2012
Study completionOct 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 173 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01568112
Sponsor's protocol ID: 109HV321
Status last verified: May 2016
First submitted: 29 Mar 2012
Last updated: 13 Jun 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

O'Gorman J, Russell HK, Li J, Phillips G, Kurukulasuriya NC, Viglietta V. Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl Fumarate. Clin Ther. 2015 Jul 1;37(7):1402-1419.e5. doi: 10.1016/j.clinthera.2015.03.028. Epub 2015 May 19.
PubMed 25999183

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Phase 3b Study to Evaluate Effects of Aspirin or Dose Titration on Flushing and Gastrointestinal Events Following Oral Administration of BG00012 Dosed at 240 mg BID
ClinicalTrials.gov ID: NCT01568112
Acronym / sponsor ID: 109HV321
Conditions: Healthy
Keywords: BG00012, gastrointestinal events, flushing events, dose titration, pre-medication, aspirin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 173 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: Apr 2012
Primary completion: Oct 2012 (actual)
Study completion: Oct 2012 (actual)
First posted: 2 Apr 2012 (estimated)
Results: Posted 13 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
BG00012	Experimental	Drug: BG00012 (dimethyl fumarate), Drug: BG00012 placebo, Drug: ASA placeboParticipants received BG00012 for 8 weeks (120 mg BID during the first week and 240 mg BID during the subsequent 7 weeks) and premedication with ASA placebo during the first 4 weeks.
Placebo	Placebo comparator	Drug: BG00012 placebo, Drug: ASA placeboParticipants received BG00012 placebo for 8 weeks and premedication with ASA placebo during the first 4 weeks.
BG00012 + ASA	Experimental	Drug: BG00012 (dimethyl fumarate), Drug: BG00012 placebo, Drug: ASAParticipants received BG00012 for 8 weeks (120 mg BID during the first week and 240 mg BID during the subsequent 7 weeks) and premedication with ASA during the first 4 weeks.
BG00012 Slow Titration	Experimental	Drug: BG00012 (dimethyl fumarate), Drug: BG00012 placebo, Drug: ASA placeboParticipants received BG00012 for 8 weeks (120 mg once daily [QD] during Week 1, 120 mg BID during Week 2, 240 mg AM/120mg PM during Week 3, and 240 mg BID during Week 4, and 240 mg BID during Weeks 5 to 8) and premedication with ASA placebo during the first 4 weeks.

Who may qualify

Ages: 25 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Must give written informed consent and any authorizations required by local law
Must have a body mass index (BMI) of between 18.0 to 34.0 kg/m^2,inclusive.
Ability to complete the tolerability scales by accurately using the hand-held subject reporting device
Subjects of childbearing potential must be willing to practice effective contraception

Key exclusion criteria (5 listed)

History of clinically significant diseases
History of severe allergic or anaphylactic reactions
Intolerance to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
Diarrhea, constipation, abdominal pain, flushing or nausea within 28 days prior to Day 1
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BG00012 (dimethyl fumarate)Also: BG-12, oral fumarate, DMFEach capsule contains 120 mg dimethyl fumarate (DMF). Fast titration involves taking one 120 mg capsule in the morning and one in the evening (240 mg daily) for one week, and then escalating to a dose of 480 mg daily (two capsules morning and evening) for the remainder of the study.Slow titration expands the dose escalation time to 4 weeks.	Drug	BG00012, BG00012 + ASA, BG00012 Slow Titration
BG00012 placeboPlacebo matching BG00012	Drug	BG00012, BG00012 + ASA, BG00012 Slow Titration, Placebo
ASAAlso: acetylsalicylic acid, aspirin325 mg microcoated aspirin (ASA)	Drug	BG00012 + ASA
ASA placeboPlacebo matching aspirin	Drug	BG00012, BG00012 Slow Titration, Placebo

Primary outcome

Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)
Time frame: Day 1 to Week 8
Participant-reported flushing side effect events during the treatment period 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).
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS
Time frame: Week 1 to Week 4
Participant-reported flushing side effect events during Weeks 1 to 4 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).
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS
Time frame: Week 5 to Week 8
Participant-reported flushing side effect events during Weeks 1 to 4 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 1 to 4 of Treatment (Combined), as Assessed by MFSS
Time frame: Day 1 to Week 4
Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, 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 to 8 of Treatment (Combined), as Assessed by MFSS
Time frame: Week 5 to Week 8
Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, 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).
Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Time frame: Day 2 to Week 8
Participant-reported flushing events during the overall treatment period, 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 events reported in the 24 hours after the first dose on Day 1.
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS
Time frame: Day 2 to Week 4
Participant-reported flushing events during Weeks 1 to 4 of treatment (combined), 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 events reported in the 24 hours after the first dose on Day 1.
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS
Time frame: Week 5 to Week 8
Participant-reported flushing events during Weeks 5 to 8 of treatment (combined), 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 Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)
Time frame: Day 1 to Week 8
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
Time frame: Day 1 to Week 4
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
Time frame: Week 5 to Week 8
The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence.
Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
Time frame: Day 1 to Week 4
Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.
Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
Time frame: Week 5 to Week 8
Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.
Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Time frame: Day 1 to Week 8
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.
Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Time frame: Week 1 to Week 4
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.
Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Time frame: Week 5 to Week 8
The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration.

12 secondary outcomes

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)
Time frame: Day 1 up to end of Safety Follow-up (9 weeks)
Clinical Laboratory Shifts From Baseline in Reported Values: Hematology
Time frame: Day 1 to Week 8
Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
Time frame: Day 1 to Week 8
Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis
Time frame: Day 1 to Week 8
Number of Participants With Abnormalities in Vital Signs
Time frame: Day 1 to Week 8
Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
Time frame: Day 1 to Week 8
Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
Time frame: Day 1 to Week 8
Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS
Time frame: Week 1 to Week 4
Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS
Time frame: Week 5 to Week 8
Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS
Time frame: Day 1 to Week 8
Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS
Time frame: Week 1 to Week 4
Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS
Time frame: Week 5 to Week 8

Results and safety

Results posted to the registry on 13 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	44	39
BG00012	44	36
BG00012 + ASA	43	36
BG00012 Slow Titration	42	30

Primary outcome: Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)

Time frame: Day 1 to Week 8. Number. Unit: percentage of participants

Measure	Placebo n = 44	BG00012 n = 43	BG00012 + ASA n = 43	BG00012 Slow Titration n = 42
Overall flushing events	41	91	81	98
Overall redness events	27	86	77	90
Overall warmth events	41	93	84	98
Overall tingling events	23	88	67	86
Overall itching events	20	86	72	98

BG00012 vs BG00012 + ASA: Difference in percentage: -9 (95% CI -30.8 to 12.9)
BG00012 vs BG00012 Slow Titration: Difference in percentage: 7 (95% CI -14.1 to 27.8)
BG00012 vs BG00012 + ASA: Difference in percentage: -9 (95% CI -30.8 to 12.9)

Population analysed: Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.

Primary outcome: Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS

Time frame: Week 1 to Week 4. Number. Unit: percentage of participants

Measure	Placebo n = 44	BG00012 n = 43	BG00012 + ASA n = 43	BG00012 Slow Titration n = 42
Overall flushing events	41	86	72	98
Overall redness events	25	81	63	88
Overall warmth events	41	88	67	95
Overall tingling events	23	84	51	83
Overall itching events	16	77	56	95

BG00012 vs BG00012 + ASA: Difference in percentage: -14 (95% CI -35.2 to 8.3)
BG00012 vs BG00012 Slow Titration: Difference in percentage: 12 (95% CI -9.5 to 32.2)
BG00012 vs BG00012 + ASA: Difference in percentage: -19 (95% CI -39.6 to 3.7)

Population analysed: Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.

Primary outcome: Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS

Time frame: Week 5 to Week 8. Number. Unit: percentage of participants

Measure	Placebo n = 41	BG00012 n = 37	BG00012 + ASA n = 36	BG00012 Slow Titration n = 33
Overall flushing events	24	86	72	85
Overall redness events	15	78	64	79
Overall warmth events	17	86	75	82
Overall tingling events	15	81	64	70
Overall itching events	22	78	58	61

BG00012 vs BG00012 + ASA: Difference in percentage: -14 (95% CI -35.6 to 9.2)
BG00012 vs BG00012 Slow Titration: Difference in percentage: -2 (95% CI -24.7 to 21.7)
BG00012 vs BG00012 + ASA: Difference in percentage: -14 (95% CI -35.6 to 9.2)

Population analysed: Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.

Primary outcome: Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS

Time frame: Day 1 to Week 4. Mean (Standard Deviation). Unit: units on a scale

Measure	Placebo n = 44	BG00012 n = 43	BG00012 + ASA n = 43	BG00012 Slow Titration n = 42
Overall flushing	1.2 (1.70)	4.4 (2.68)	2.4 (2.26)	5.6 (2.24)
Redness	0.7 (1.33)	3.8 (2.76)	1.6 (1.75)	5.1 (2.93)
Warmth	1.2 (1.76)	4.0 (2.55)	2.3 (2.17)	5.2 (2.37)
Tingling	0.5 (1.00)	3.4 (2.21)	1.6 (2.13)	4.0 (2.62)
Itching	0.5 (1.21)	3.2 (2.45)	1.3 (1.72)	4.3 (2.10)

BG00012 vs BG00012 + ASA: Mean difference: -1.9 (95% CI -3.0 to -0.9)
BG00012 vs BG00012 Slow Titration: Mean difference: 1.2 (95% CI 0.2 to 2.3)
BG00012 vs BG00012 + ASA: Mean difference: -2.2 (95% CI -3.2 to -1.2)

Population analysed: Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs: from the administration of the first dose of study treatment to the Safety Follow-up (approximately 9 weeks). SAEs: from signing of informed consent to the Safety Follow-up (up to approximately 13 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 44 (0%)	5 of 44 (11.4%)	Not reported
BG00012	1 of 43 (2.3%)	12 of 43 (27.9%)	Not reported
BG00012 + ASA	0 of 43 (0%)	15 of 43 (34.9%)	Not reported
BG00012 Slow Titration	0 of 42 (0%)	12 of 42 (28.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25999183O'Gorman J, Russell HK, Li J, Phillips G, Kurukulasuriya NC, Viglietta V. Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl Fumarate. Clin Ther. 2015 Jul 1;37(7):1402-1419.e5. doi: 10.1016/j.clinthera.2015.03.028. Epub 2015 May 19.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BG00012 (dimethyl fumarate) and ASA in people with Healthy, run by Biogen at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS) (time frame: Day 1 to Week 8). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01568112, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2016.