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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 BG0001

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.

Detailed Summary:
Sponsor: Biogen

Current 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 effe

    Original Primary Outcome:

    • The incidence and severity of flushing events using the modified flushing scale and the modified global flushing scale [ Time Frame: An estimated duration of 8 weeks ]
    • Number of Participants with Adverse Events as a measure of safety and tolerability [ Time Frame: An estimated duration of 9 weeks ]
    • The incidence and severity of gastrointestinal events by using modified acute gastrointestinal scale and modified overall gastrointestinal symptom scale [ Time Frame: An estimated duration of 8 weeks ]


    Current Secondary Outcome:

    • 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.
    • 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
    • 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.
    • 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.
    • 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
    • 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.'
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.

      Original Secondary Outcome:

      Information By: Biogen

      Dates:
      Date Received: March 29, 2012
      Date Started: April 2012
      Date Completion:
      Last Updated: May 4, 2016
      Last Verified: May 2016