Clinical trial NCT01568112: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Keywords: BG00012
gastrointestinal events
flushing events
dose titration
pre-medication
aspirin
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2012-04-02
Enrollment: 173
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)
timeFrame: Day 1 to Week 8
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS
timeFrame: Week 1 to Week 4
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS
timeFrame: Week 5 to Week 8
measure: Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS
timeFrame: Day 1 to Week 4
measure: Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS
timeFrame: Week 5 to Week 8
measure: Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
timeFrame: Day 2 to Week 8
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS
timeFrame: Day 2 to Week 4
measure: Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS
timeFrame: Week 5 to Week 8
measure: Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)
timeFrame: Day 1 to Week 8
measure: Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
timeFrame: Day 1 to Week 4
measure: Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
timeFrame: Week 5 to Week 8
measure: Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
timeFrame: Day 1 to Week 4
measure: Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
timeFrame: Week 5 to Week 8
measure: Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
timeFrame: Day 1 to Week 8
measure: Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
timeFrame: Week 1 to Week 4
measure: Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
timeFrame: Week 5 to Week 8
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)
timeFrame: Day 1 up to end of Safety Follow-up (9 weeks)
measure: Clinical Laboratory Shifts From Baseline in Reported Values: Hematology
timeFrame: Day 1 to Week 8
measure: Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
timeFrame: Day 1 to Week 8
measure: Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis
timeFrame: Day 1 to Week 8
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: Day 1 to Week 8
measure: Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
timeFrame: Day 1 to Week 8
measure: Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
timeFrame: Day 1 to Week 8
measure: Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS
timeFrame: Week 1 to Week 4
measure: Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS
timeFrame: Week 5 to Week 8
measure: Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS
timeFrame: Day 1 to Week 8
measure: Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS
timeFrame: Week 1 to Week 4
measure: Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS
timeFrame: Week 5 to Week 8
Other outcomes:
Locations:
city: St Paul
country: United States
facility: Research Site
state: Minnesota
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
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.