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

Primary Purpose

Healthy

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
BG00012 (dimethyl fumarate)
BG00012 placebo
ASA
ASA placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Healthy focused on measuring BG00012, gastrointestinal events, flushing events, dose titration, pre-medication, aspirin

Eligibility Criteria

25 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria:

  • 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:

  • 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.

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

BG00012

Placebo

BG00012 + ASA

BG00012 Slow Titration

Arm Description

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.

Participants received BG00012 placebo for 8 weeks and premedication with ASA placebo during the first 4 weeks.

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.

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.

Outcomes

Primary Outcome Measures

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).
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).
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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
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
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.
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.
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
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.'
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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 29, 2012
Last Updated
May 4, 2016
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01568112
Brief Title
Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl Fumarate
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
Keywords
BG00012, gastrointestinal events, flushing events, dose titration, pre-medication, aspirin

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
173 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BG00012
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received BG00012 placebo for 8 weeks and premedication with ASA placebo during the first 4 weeks.
Arm Title
BG00012 + ASA
Arm Type
Experimental
Arm Description
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.
Arm Title
BG00012 Slow Titration
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BG00012 (dimethyl fumarate)
Other Intervention Name(s)
BG-12, oral fumarate, DMF
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BG00012 placebo
Intervention Description
Placebo matching BG00012
Intervention Type
Drug
Intervention Name(s)
ASA
Other Intervention Name(s)
acetylsalicylic acid, aspirin
Intervention Description
325 mg microcoated aspirin (ASA)
Intervention Type
Drug
Intervention Name(s)
ASA placebo
Intervention Description
Placebo matching aspirin
Primary Outcome Measure Information:
Title
Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)
Description
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).
Time Frame
Day 1 to Week 8
Title
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS
Description
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).
Time Frame
Week 1 to Week 4
Title
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS
Description
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).
Time Frame
Week 5 to Week 8
Title
Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS
Description
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).
Time Frame
Day 1 to Week 4
Title
Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS
Description
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).
Time Frame
Week 5 to Week 8
Title
Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Description
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.
Time Frame
Day 2 to Week 8
Title
Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS
Description
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.
Time Frame
Day 2 to Week 4
Title
Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS
Description
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.
Time Frame
Week 5 to Week 8
Title
Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)
Description
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.
Time Frame
Day 1 to Week 8
Title
Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
Description
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.
Time Frame
Day 1 to Week 4
Title
Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
Description
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.
Time Frame
Week 5 to Week 8
Title
Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
Description
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.
Time Frame
Day 1 to Week 4
Title
Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
Description
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.
Time Frame
Week 5 to Week 8
Title
Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Description
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.
Time Frame
Day 1 to Week 8
Title
Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Description
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.
Time Frame
Week 1 to Week 4
Title
Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
Description
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.
Time Frame
Week 5 to Week 8
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)
Description
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.
Time Frame
Day 1 up to end of Safety Follow-up (9 weeks)
Title
Clinical Laboratory Shifts From Baseline in Reported Values: Hematology
Description
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
Time Frame
Day 1 to Week 8
Title
Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
Description
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.
Time Frame
Day 1 to Week 8
Title
Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis
Description
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.
Time Frame
Day 1 to Week 8
Title
Number of Participants With Abnormalities in Vital Signs
Description
↑=increase; ↓=decrease; BL=baseline; bpm=beats per minute; SBP=systolic blood pressure; DBP=diastolic blood pressure; b/m=breaths per minute
Time Frame
Day 1 to Week 8
Title
Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
Description
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.'
Time Frame
Day 1 to Week 8
Title
Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
Description
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.
Time Frame
Day 1 to Week 8
Title
Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS
Description
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.
Time Frame
Week 1 to Week 4
Title
Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS
Description
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.
Time Frame
Week 5 to Week 8
Title
Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS
Description
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.
Time Frame
Day 1 to Week 8
Title
Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS
Description
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.
Time Frame
Week 1 to Week 4
Title
Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS
Description
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.
Time Frame
Week 5 to Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: 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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
St Paul
State/Province
Minnesota
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25999183
Citation
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.
Results Reference
result

Learn more about this trial

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

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