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

NCT01568112 | Completed Phase 3 Results

• 1 other identifier: 109HV321
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

BG00012; gastrointestinal events; flushing events; dose titration; pre-medication; aspirin

Outcome Measures

Primary Outcomes (16)

• 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).

  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).

  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).

  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).

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Week 5 to Week 8

Secondary Outcomes (12)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)

  Day 1 up to end of Safety Follow-up (9 weeks)

• Clinical Laboratory Shifts From Baseline in Reported Values: Hematology

  Day 1 to Week 8

• Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry

  Day 1 to Week 8

• Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis

  Day 1 to Week 8

• Number of Participants With Abnormalities in Vital Signs

  Day 1 to Week 8

Study Arms (4)

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.

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.

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.

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.

Drug: BG00012 (dimethyl fumarate); Drug: BG00012 placebo; Drug: ASA placebo

Interventions

BG00012 (dimethyl fumarate) DRUG

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.

Also known as: BG-12, oral fumarate, DMF

BG00012; BG00012 + ASA; BG00012 Slow Titration

BG00012 placebo DRUG

Placebo matching BG00012

BG00012; BG00012 + ASA; BG00012 Slow Titration; Placebo

ASA DRUG

325 mg microcoated aspirin (ASA)

Also known as: acetylsalicylic acid, aspirin

BG00012 + ASA

ASA placebo DRUG

Placebo matching aspirin

BG00012; BG00012 Slow Titration; Placebo

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Research Site

Saint Paul, Minnesota, United States

Location

Related Publications (1)

• 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.

  PMID: 25999183 RESULT

MeSH Terms

Interventions

Dimethyl Fumarate; Fumarates; Aspirin

Intervention Hierarchy (Ancestors)

Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 2, 2012
• Study Start: April 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: June 13, 2016
• Results First Posted: June 13, 2016

Record last verified: 2016-05

Locations

US (1)