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

May 4, 2016 updated by: Biogen

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

173

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • St Paul, Minnesota, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BG00012
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.
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.
Other Names:
  • DMF
  • BG-12
  • oral fumarate
Placebo matching BG00012
Placebo matching aspirin
Placebo Comparator: Placebo
Participants received BG00012 placebo for 8 weeks and premedication with ASA placebo during the first 4 weeks.
Placebo matching BG00012
Placebo matching aspirin
Experimental: BG00012 + ASA
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.
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.
Other Names:
  • DMF
  • BG-12
  • oral fumarate
Placebo matching BG00012
325 mg microcoated aspirin (ASA)
Other Names:
  • acetylsalicylic acid
  • aspirin
Experimental: BG00012 Slow Titration
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.
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.
Other Names:
  • DMF
  • BG-12
  • oral fumarate
Placebo matching BG00012
Placebo matching aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Day 1 to Week 8
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).
Week 1 to Week 4
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).
Week 5 to Week 8
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).
Day 1 to Week 4
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).
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)
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.
Day 2 to Week 8
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.
Day 2 to Week 4
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.
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)
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.
Day 1 to Week 8
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.
Day 1 to Week 4
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.
Week 5 to Week 8
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.
Day 1 to Week 4
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.
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)
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.
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)
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.
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)
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.
Week 5 to Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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
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
Day 1 to Week 8
Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
Time Frame: Day 1 to Week 8
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.
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 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.
Day 1 to Week 8
Number of Participants With Abnormalities in Vital Signs
Time Frame: Day 1 to Week 8
↑=increase; ↓=decrease; BL=baseline; bpm=beats per minute; SBP=systolic blood pressure; DBP=diastolic blood pressure; b/m=breaths per minute
Day 1 to Week 8
Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
Time Frame: Day 1 to Week 8
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.'
Day 1 to Week 8
Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
Time Frame: Day 1 to Week 8
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.
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
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.
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
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.
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 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.
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 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.
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
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.
Week 5 to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

March 29, 2012

First Submitted That Met QC Criteria

March 30, 2012

First Posted (Estimate)

April 2, 2012

Study Record Updates

Last Update Posted (Estimate)

June 13, 2016

Last Update Submitted That Met QC Criteria

May 4, 2016

Last Verified

May 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Healthy

Clinical Trials on BG00012 (dimethyl fumarate)

3
Subscribe