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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

Sponsor
Biogen (Industry)
Overall Status
Completed
CT.gov ID
NCT01568112
Collaborator
(none)
173
Enrollment
1
Location
4
Arms
6
Duration (Months)
28.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: BG00012 (dimethyl fumarate)
  • Drug: BG00012 placebo
  • Drug: ASA
  • Drug: ASA placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
173 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
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 Start Date :
Apr 1, 2012
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Oct 1, 2012

Arms and Interventions

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.

Drug: BG00012 (dimethyl fumarate)
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:
  • BG-12
  • oral fumarate
  • DMF

    • Drug: BG00012 placebo
    Placebo matching BG00012

    Drug: ASA placebo
    Placebo matching aspirin
    Placebo Comparator: Placebo

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

    Drug: BG00012 placebo
    Placebo matching BG00012

    Drug: ASA placebo
    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.

    Drug: BG00012 (dimethyl fumarate)
    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:
  • BG-12
  • oral fumarate
  • DMF

    • Drug: BG00012 placebo
    Placebo matching BG00012

    Drug: ASA
    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.

    Drug: BG00012 (dimethyl fumarate)
    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:
  • BG-12
  • oral fumarate
  • DMF

    • Drug: BG00012 placebo
    Placebo matching BG00012

    Drug: ASA placebo
    Placebo matching aspirin

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS) [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).

    2. Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS [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).

    3. Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS [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).

    4. Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS [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).

    5. Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS [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).

    6. Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS) [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.

    7. Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS [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.

    8. Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS [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.

    9. Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS) [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.

    10. Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS [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.

    11. Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS [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.

    12. Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS [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.

    13. Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS [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.

    14. Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS) [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.

    15. Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS) [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.

    16. Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS) [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.

    Secondary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs) [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.

    2. Clinical Laboratory Shifts From Baseline in Reported Values: Hematology [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

    3. Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry [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.

    4. Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis [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.

    5. Number of Participants With Abnormalities in Vital Signs [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

    6. Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results [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.'

    7. Duration of Flushing Events During the Overall Treatment Period, Based on MFSS [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.

    8. Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS [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.

    9. Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS [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.

    10. Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS [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.

    11. Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS [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.

    12. Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site St Paul Minnesota United States

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT01568112
    Other Study ID Numbers:
    • 109HV321
    First Posted:
    Apr 2, 2012
    Last Update Posted:
    Jun 13, 2016
    Last Verified:
    May 1, 2016
    Keywords provided by Biogen
    BG00012
    gastrointestinal events
    flushing events
    dose titration
    pre-medication
    aspirin
    Additional relevant MeSH terms:
    Flushing
    Aspirin
    Dimethyl Fumarate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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.
    Period Title: Overall Study
    STARTED 44 44 43 42
    COMPLETED 39 36 36 30
    NOT COMPLETED 5 8 7 12

    Baseline Characteristics

    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration Total
    Arm/Group Description 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 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. Total of all reporting groups
    Overall Participants 44 43 43 42 172
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    35.5
    (8.78)
    39.0
    (9.61)
    38.1
    (10.29)
    36.2
    (9.33)
    37.2
    (9.54)
    Age, Customized (participants) [Number]
    25 to 34 years
    22
    50%
    19
    44.2%
    17
    39.5%
    21
    50%
    79
    45.9%
    35 to 44 years
    13
    29.5%
    7
    16.3%
    13
    30.2%
    10
    23.8%
    43
    25%
    45 to 55 years
    9
    20.5%
    17
    39.5%
    13
    30.2%
    11
    26.2%
    50
    29.1%
    Sex: Female, Male (Count of Participants)
    Female
    14
    31.8%
    21
    48.8%
    17
    39.5%
    20
    47.6%
    72
    41.9%
    Male
    30
    68.2%
    22
    51.2%
    26
    60.5%
    22
    52.4%
    100
    58.1%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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.
    Measure Participants 44 43 43 42
    Overall flushing events
    41
    93.2%
    91
    211.6%
    81
    188.4%
    98
    233.3%
    Overall redness events
    27
    61.4%
    86
    200%
    77
    179.1%
    90
    214.3%
    Overall warmth events
    41
    93.2%
    93
    216.3%
    84
    195.3%
    98
    233.3%
    Overall tingling events
    23
    52.3%
    88
    204.7%
    67
    155.8%
    86
    204.8%
    Overall itching events
    20
    45.5%
    86
    200%
    72
    167.4%
    98
    233.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -9
    Confidence Interval (2-Sided) 95%
    -30.8 to 12.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 7
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -9
    Confidence Interval (2-Sided) 95%
    -30.8 to 12.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 4
    Confidence Interval (2-Sided) 95%
    -16.4 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -21
    Confidence Interval (2-Sided) 95%
    -41.7 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -3
    Confidence Interval (2-Sided) 95%
    -23.3 to 18.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -14
    Confidence Interval (2-Sided) 95%
    -35.2 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 12
    Confidence Interval (2-Sided) 95%
    -9.5 to 32.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -9
    Confidence Interval (2-Sided) 95%
    -30.8 to 12.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 5
    Confidence Interval (2-Sided) 95%
    -16.4 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Overall flushing events
    41
    93.2%
    86
    200%
    72
    167.4%
    98
    233.3%
    Overall redness events
    25
    56.8%
    81
    188.4%
    63
    146.5%
    88
    209.5%
    Overall warmth events
    41
    93.2%
    88
    204.7%
    67
    155.8%
    95
    226.2%
    Overall tingling events
    23
    52.3%
    84
    195.3%
    51
    118.6%
    83
    197.6%
    Overall itching events
    16
    36.4%
    77
    179.1%
    56
    130.2%
    95
    226.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -14
    Confidence Interval (2-Sided) 95%
    -35.2 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 12
    Confidence Interval (2-Sided) 95%
    -9.5 to 32.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -19
    Confidence Interval (2-Sided) 95%
    -39.6 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 7
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -21
    Confidence Interval (2-Sided) 95%
    -41.7 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 7
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -33
    Confidence Interval (2-Sided) 95%
    -52.2 to -10.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0
    Confidence Interval (2-Sided) 95%
    -21.0 to 21.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -21
    Confidence Interval (2-Sided) 95%
    -41.7 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18
    Confidence Interval (2-Sided) 95%
    -2.4 to 38.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    3. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Overall flushing events
    24
    54.5%
    86
    200%
    72
    167.4%
    85
    202.4%
    Overall redness events
    15
    34.1%
    78
    181.4%
    64
    148.8%
    79
    188.1%
    Overall warmth events
    17
    38.6%
    86
    200%
    75
    174.4%
    82
    195.2%
    Overall tingling events
    15
    34.1%
    81
    188.4%
    64
    148.8%
    70
    166.7%
    Overall itching events
    22
    50%
    78
    181.4%
    58
    134.9%
    61
    145.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -14
    Confidence Interval (2-Sided) 95%
    -35.6 to 9.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2
    Confidence Interval (2-Sided) 95%
    -24.7 to 21.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -14
    Confidence Interval (2-Sided) 95%
    -35.6 to 9.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0
    Confidence Interval (2-Sided) 95%
    -22.9 to 23.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -11
    Confidence Interval (2-Sided) 95%
    -33.0 to 11.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -5
    Confidence Interval (2-Sided) 95%
    -27.5 to 18.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -17
    Confidence Interval (2-Sided) 95%
    -38.1 to 6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -11
    Confidence Interval (2-Sided) 95%
    -34.2 to 12.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -20
    Confidence Interval (2-Sided) 95%
    -40.6 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -18
    Confidence Interval (2-Sided) 95%
    -40.2 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    4. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Overall flushing
    1.2
    (1.70)
    4.4
    (2.68)
    2.4
    (2.26)
    5.6
    (2.24)
    Redness
    0.7
    (1.33)
    3.8
    (2.76)
    1.6
    (1.75)
    5.1
    (2.93)
    Warmth
    1.2
    (1.76)
    4.0
    (2.55)
    2.3
    (2.17)
    5.2
    (2.37)
    Tingling
    0.5
    (1.00)
    3.4
    (2.21)
    1.6
    (2.13)
    4.0
    (2.62)
    Itching
    0.5
    (1.21)
    3.2
    (2.45)
    1.3
    (1.72)
    4.3
    (2.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.0 to -0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    0.2 to 2.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -3.2 to -1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.50
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012 + ASA, BG00012 Slow Titration
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    0.1 to 2.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.62
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -2.8 to -0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.51
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012 + ASA, BG00012 Slow Titration
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    0.1 to 2.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -2.7 to -0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012 + ASA, BG00012 Slow Titration
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -0.4 to 1.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.52
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -2.8 to -1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012 + ASA, BG00012 Slow Titration
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    0.2 to 2.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.50
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    5. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Overall flushing
    0.9
    (1.67)
    3.8
    (2.48)
    3.3
    (2.78)
    3.1
    (2.26)
    Redness
    0.4
    (1.14)
    3.6
    (2.73)
    2.9
    (2.67)
    2.9
    (2.30)
    Warmth
    0.8
    (1.79)
    3.9
    (2.53)
    3.1
    (2.50)
    2.9
    (2.15)
    Tingling
    0.3
    (0.82)
    3.3
    (2.50)
    2.3
    (2.36)
    2.2
    (1.96)
    Itching
    0.7
    (1.58)
    3.1
    (2.71)
    2.3
    (2.52)
    1.8
    (2.04)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.7 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.62
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.8 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.57
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.63
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Redness events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.9 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.61
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Warmth events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.1 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.56
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -2.2 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.57
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Tingling events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.2 to -0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.1 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.61
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Itching events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -2.4 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.58
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    6. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 42 42
    Number [percentage of participants]
    43
    97.7%
    86
    200%
    74
    172.1%
    93
    221.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -12
    Confidence Interval (2-Sided) 95%
    -32.2 to 9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Overall flushing events
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 7
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    7. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 42 42
    Number [percentage of participants]
    41
    93.2%
    84
    195.3%
    62
    144.2%
    90
    214.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -22
    Confidence Interval (2-Sided) 95%
    -41.0 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 7
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    8. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Number [percentage of participants]
    24
    54.5%
    86
    200%
    67
    155.8%
    85
    202.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -20
    Confidence Interval (2-Sided) 95%
    -40.6 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2
    Confidence Interval (2-Sided) 95%
    -24.7 to 21.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    9. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Number [percentage of participants]
    73
    165.9%
    81
    188.4%
    81
    188.4%
    86
    204.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0
    Confidence Interval (2-Sided) 95%
    -22.0 to 22.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 4
    Confidence Interval (2-Sided) 95%
    -16.4 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    10. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Number [percentage of participants]
    66
    150%
    81
    188.4%
    79
    183.7%
    79
    188.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2
    Confidence Interval (2-Sided) 95%
    -24.2 to 19.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -3
    Confidence Interval (2-Sided) 95%
    -23.3 to 18.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    11. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Number [percentage of participants]
    41
    93.2%
    59
    137.2%
    53
    123.3%
    61
    145.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -7
    Confidence Interval (2-Sided) 95%
    -29.4 to 17.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 1
    Confidence Interval (2-Sided) 95%
    -22.1 to 24.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    12. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Nausea
    0.7
    (1.59)
    1.6
    (2.41)
    1.6
    (2.54)
    1.5
    (2.09)
    Diarrhea
    1.0
    (1.97)
    1.8
    (2.47)
    1.5
    (2.76)
    1.0
    (1.67)
    Upper abdominal pain
    0.8
    (1.38)
    1.1
    (2.16)
    1.7
    (2.71)
    1.4
    (2.47)
    Lower abdominal pain
    0.5
    (1.21)
    1.4
    (2.14)
    1.3
    (2.32)
    1.2
    (2.12)
    Vomiting
    0.2
    (0.75)
    0.3
    (1.28)
    0.3
    (1.63)
    0.2
    (1.10)
    Indigestion
    0.7
    (1.29)
    0.9
    (1.83)
    0.6
    (1.26)
    0.9
    (1.97)
    Constipation
    0.4
    (1.45)
    0.9
    (2.23)
    0.6
    (1.45)
    0.9
    (1.85)
    Bloating
    0.5
    (1.17)
    1.1
    (1.96)
    1.3
    (2.08)
    1.0
    (1.88)
    Flatulence
    1.3
    (1.73)
    1.3
    (2.03)
    1.4
    (1.76)
    1.6
    (2.20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.1 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.49
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.4 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.57
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.7 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -0.5 to 1.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.7 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.50
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.48
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.26
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.44
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -0.7 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.4
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.9 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.42
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -0.7 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    13. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Nausea
    0.4
    (1.51)
    0.9
    (1.79)
    0.8
    (1.94)
    0.9
    (1.65)
    Diarrhea
    1.0
    (2.01)
    1.4
    (2.29)
    0.8
    (2.13)
    0.7
    (1.42)
    Upper abdominal pain
    0.6
    (1.69)
    0.5
    (1.50)
    0.4
    (1.21)
    0.6
    (1.56)
    Lower abdominal pain
    0.6
    (1.48)
    0.4
    (1.42)
    0.5
    (1.38)
    0.9
    (1.72)
    Vomiting
    0.2
    (1.41)
    0.1
    (0.82)
    0.1
    (0.83)
    0.0
    (0.00)
    Indigestion
    0.4
    (1.26)
    0.5
    (1.32)
    0.5
    (1.38)
    0.4
    (1.06)
    Constipation
    0.4
    (1.20)
    0.1
    (0.59)
    0.6
    (1.63)
    0.3
    (1.05)
    Bloating
    0.5
    (1.23)
    0.7
    (1.61)
    0.7
    (1.55)
    0.8
    (1.52)
    Flatulence
    0.8
    (1.65)
    1.2
    (2.04)
    0.4
    (1.08)
    0.9
    (1.54)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.44
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.7 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.52
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.7 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -0.2 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.19
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -0.1 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.20
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.44
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    14. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 42 42
    Number [percentage of participants]
    59
    134.1%
    70
    162.8%
    79
    183.7%
    79
    188.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 9
    Confidence Interval (2-Sided) 95%
    -11.8 to 30.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 9
    Confidence Interval (2-Sided) 95%
    -11.8 to 30.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    15. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 42 42
    Number [percentage of participants]
    57
    129.5%
    65
    151.2%
    67
    155.8%
    71
    169%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 2
    Confidence Interval (2-Sided) 95%
    -18.8 to 23.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 6
    Confidence Interval (2-Sided) 95%
    -14.1 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    16. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication and who had at least 1 diary entry of the relevant questionnaire data during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 41 37 36 33
    Number [percentage of participants]
    34
    77.3%
    59
    137.2%
    50
    116.3%
    58
    138.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -9
    Confidence Interval (2-Sided) 95%
    -32.1 to 14.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2
    Confidence Interval (2-Sided) 95%
    -25.0 to 21.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    17. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo).
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Any event
    24
    54.5%
    24
    55.8%
    26
    60.5%
    26
    61.9%
    Moderate or severe event
    10
    22.7%
    13
    30.2%
    12
    27.9%
    11
    26.2%
    Severe event
    0
    0%
    4
    9.3%
    4
    9.3%
    1
    2.4%
    Related event
    8
    18.2%
    17
    39.5%
    16
    37.2%
    18
    42.9%
    Serious event
    0
    0%
    1
    2.3%
    0
    0%
    0
    0%
    Discontinuation of treatment due to an event
    2
    4.5%
    4
    9.3%
    6
    14%
    3
    7.1%
    Withdrawal from study due to an event
    2
    4.5%
    4
    9.3%
    6
    14%
    3
    7.1%
    18. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo); n=number of participants whose baseline value was not low (or high) and who had at least 1 post-baseline value.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    White blood cells: shift to low; n=43, 43, 43, 41
    0
    0%
    2
    4.7%
    0
    0%
    0
    0%
    White blood cells: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    Neutrophils abs: shift to low; n=42, 42, 42, 41
    3
    6.8%
    6
    14%
    2
    4.7%
    2
    4.8%
    Neutrophils abs: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    Lymphocytes abs: shift to low; n=43, 43, 43, 41
    1
    2.3%
    5
    11.6%
    2
    4.7%
    3
    7.1%
    Lymphocytes abs: shift to high; n=44, 43, 42, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Monocytes abs: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Monocytes abs: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Eosinophils abs: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Eosinophils abs: shift to high; n=44, 43, 43, 42
    0
    0%
    5
    11.6%
    6
    14%
    6
    14.3%
    Basophils abs: shift to high; n=44, 43, 43, 42
    0
    0%
    1
    2.3%
    1
    2.3%
    0
    0%
    Red blood cells: shift to low; n=44, 43, 43, 40
    0
    0%
    2
    4.7%
    0
    0%
    0
    0%
    Red blood cells: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hemoglobin: shift to low; n=43, 41, 43, 42
    1
    2.3%
    3
    7%
    1
    2.3%
    0
    0%
    Hemoglobin: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hematocrit: shift to low; n=44, 43, 43, 42
    0
    0%
    2
    4.7%
    0
    0%
    0
    0%
    Hematocrit: shift to high; n=43, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    Platelets: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Platelets: shift to high; n=44, 41, 43, 42
    0
    0%
    0
    0%
    1
    2.3%
    1
    2.4%
    19. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo); n=number of participants whose baseline value was not low (or high) and who had at least 1 post-baseline value.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 44 43
    ALP: shift to high; n=44, 42, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ALT: shift to high; n=44, 42, 43, 42
    1
    2.3%
    2
    4.7%
    5
    11.6%
    2
    4.8%
    AST: shift to high; n=44, 43, 43, 41
    2
    4.5%
    3
    7%
    4
    9.3%
    1
    2.4%
    GGT: shift to high; n=44, 41, 43, 42
    0
    0%
    0
    0%
    2
    4.7%
    0
    0%
    LDH: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    LDH: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    Total bilirubin: shift to high; n=44, 42, 42, 40
    1
    2.3%
    1
    2.3%
    0
    0%
    1
    2.4%
    BUN: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    BUN: shift to high; n=44, 43, 41, 42
    1
    2.3%
    0
    0%
    1
    2.3%
    1
    2.4%
    Creatinine: shift to low; n=44, 43, 43, 42
    0
    0%
    1
    2.3%
    0
    0%
    0
    0%
    Creatinine: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Uric Acid: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Uric Acid: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sodium: shift to low; n=44, 43, 43, 42
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    Sodium: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    Potassium: shift to low: n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Potassium: shift to high: n=44, 42, 42, 41
    1
    2.3%
    1
    2.3%
    1
    2.3%
    0
    0%
    Chloride: shift to low; n=44, 43, 43, 42
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    Chloride: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Bicarbonate: shift to low; n=44, 43, 43, 42
    1
    2.3%
    1
    2.3%
    1
    2.3%
    0
    0%
    Bicarbonate: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Calcium: shift to low; n=44, 42, 43, 42
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    Calcium: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Glucose: shift to low; n=43, 43, 41, 41
    3
    6.8%
    1
    2.3%
    1
    2.3%
    2
    4.8%
    Glucose: shift to high; n=44, 43, 43, 42
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    Magnesium: shift to low; n=44, 43, 43, 42
    1
    2.3%
    0
    0%
    0
    0%
    1
    2.4%
    Magnesium: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Phosphorus: shift to low; n=44, 43, 43, 41
    0
    0%
    1
    2.3%
    0
    0%
    0
    0%
    Phosphorus: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    Albumin: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Albumin: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Direct bilirubin: shift to high; n=44, 43, 43, 40
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Total protein: shift to low; n=44, 41, 43, 41
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    Total protein: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo); n=number of participants whose baseline value was not low (or high or positive) and who had at least 1 post-baseline value.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Specific gravity: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Specific gravity: shift to high; n=44, 42, 43, 42
    0
    0%
    0
    0%
    2
    4.7%
    0
    0%
    pH: shift to low; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    pH: shift to high; n=44, 43, 43, 42
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Blood: shift to positive; n=42, 39, 39, 42
    3
    6.8%
    6
    14%
    1
    2.3%
    2
    4.8%
    Color: shift to positive; n=41, 43, 41, 39
    2
    4.5%
    1
    2.3%
    4
    9.3%
    5
    11.9%
    Glucose: shift to positive; n=44, 43, 43, 41
    0
    0%
    2
    4.7%
    1
    2.3%
    0
    0%
    Ketones: shift to positive; n=44, 43, 43, 42
    1
    2.3%
    7
    16.3%
    9
    20.9%
    6
    14.3%
    Protein: shift to positive; n=44, 41, 43, 41
    0
    0%
    1
    2.3%
    1
    2.3%
    1
    2.4%
    Microscopic RBC; n=44, 40, 40, 41
    3
    6.8%
    4
    9.3%
    1
    2.3%
    2
    4.8%
    Microscopic WBC; n=43, 40, 41, 42
    4
    9.1%
    9
    20.9%
    3
    7%
    3
    7.1%
    21. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo); n=number of participants who had a baseline value and had at least 1 post-baseline value.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Temperature >38°C + ↑ from BL of ≥1°C
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Pulse >120 bpm or ↑ from BL of >20 bpm
    8
    18.2%
    10
    23.3%
    20
    46.5%
    17
    40.5%
    Pulse <50 bpm or ↓ from BL of >20 bpm
    11
    25%
    4
    9.3%
    3
    7%
    4
    9.5%
    SBP >180 mm Hg or ↑ from BL of >40 mm Hg
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    SBP <90 mm Hg or ↓ from BL of >30 mm Hg
    1
    2.3%
    2
    4.7%
    1
    2.3%
    1
    2.4%
    DBP >105 mm Hg or ↑ from BL of >30 mm Hg
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    DBP <50 mm Hg or ↓ from BL of >20 mm Hg
    1
    2.3%
    3
    7%
    0
    0%
    1
    2.4%
    Respiration rate >25 b/m or ↑ from BL of ≥50%
    1
    2.3%
    2
    4.7%
    3
    7%
    3
    7.1%
    Respiration rate 10 b/m or ↓ from BL of ≥50%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    22. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety population: participants who received at least 1 dose of study treatment (BG00012/BG00012 placebo); n=number of participants whose baseline value was not abnormal and who had at least 1 post-baseline value.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Shift to abnormal, not adverse event
    2
    4.5%
    3
    7%
    2
    4.7%
    4
    9.5%
    Shift to abnormal, adverse event
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    23. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants with a flushing event.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 18 39 35 41
    Mean (Standard Deviation) [minutes]
    98.4
    (92.04)
    63.2
    (34.55)
    69.8
    (78.09)
    68.9
    (52.82)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.6
    Confidence Interval (2-Sided) 95%
    -20.9 to 34.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 13.79
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.8
    Confidence Interval (2-Sided) 95%
    -14.2 to 25.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 10.03
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    24. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants with a flushing event.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 18 37 31 41
    Mean (Standard Deviation) [minutes]
    117.6
    (143.90)
    67.6
    (43.83)
    89.8
    (140.67)
    69.2
    (53.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 22.2
    Confidence Interval (2-Sided) 95%
    -26.5 to 70.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 24.40
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    -20.5 to 23.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 11.08
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    25. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants with a flushing event.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 10 32 26 28
    Mean (Standard Deviation) [minutes]
    113.2
    (160.82)
    55.7
    (32.37)
    73.2
    (66.34)
    56.0
    (35.79)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 17.5
    Confidence Interval (2-Sided) 95%
    -9.2 to 44.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 13.32
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -17.2 to 18.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.80
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    26. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the safety population who have at least 1 diary entry of the relevant questionnaire data during the visit interval; n=number of participants with the given GI episode during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Nausea; n=12, 21, 21, 22
    9.74
    (17.008)
    7.05
    (10.498)
    10.01
    (18.283)
    2.98
    (3.247)
    Diarrhea; n=20, 20 17, 15
    5.57
    (10.037)
    2.92
    (3.329)
    14.66
    (32.686)
    4.97
    (9.687)
    Upper abdominal pain; n=17, 14, 19, 19
    19.08
    (46.873)
    6.67
    (16.916)
    15.88
    (25.307)
    3.83
    (5.712)
    Lower abdominal pain; n=12, 19, 17, 16
    6.65
    (5.307)
    13.93
    (26.850)
    10.84
    (16.312)
    7.75
    (10.456)
    Vomiting; n=3, 3, 3, 2
    5.87
    (5.033)
    10.08
    (8.755)
    1.88
    (2.717)
    0.75
    (0.707)
    Indigestion; n=12, 13, 12, 12
    4.76
    (8.203)
    16.49
    (28.865)
    3.80
    (2.543)
    4.91
    (8.263)
    Constipation; n=6, 8, 13, 11
    20.49
    (12.040)
    28.20
    (35.425)
    14.26
    (9.783)
    20.90
    (18.060)
    Bloating; n=14, 14, 21, 12
    9.50
    (9.066)
    16.91
    (27.128)
    9.68
    (10.108)
    77.24
    (125.961)
    Flatulence; n=23, 20, 22, 20
    16.41
    (44.149)
    9.06
    (9.626)
    68.93
    (290.248)
    63.84
    (180.597)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.96
    Confidence Interval (2-Sided) 95%
    -6.34 to 12.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.601
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.07
    Confidence Interval (2-Sided) 95%
    -8.81 to 0.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.347
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.74
    Confidence Interval (2-Sided) 95%
    -3.15 to 26.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.335
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.05
    Confidence Interval (2-Sided) 95%
    -2.67 to 6.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.321
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.21
    Confidence Interval (2-Sided) 95%
    -6.72 to 25.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.812
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.84
    Confidence Interval (2-Sided) 95%
    -11.31 to 5.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.152
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.09
    Confidence Interval (2-Sided) 95%
    -18.36 to 12.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.516
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.18
    Confidence Interval (2-Sided) 95%
    -20.71 to 8.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.141
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.21
    Confidence Interval (2-Sided) 95%
    -22.90 to 6.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.292
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.33
    Confidence Interval (2-Sided) 95%
    -30.13 to 11.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.536
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.69
    Confidence Interval (2-Sided) 95%
    -30.02 to 4.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.376
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.58
    Confidence Interval (2-Sided) 95%
    -29.48 to 6.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.654
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.93
    Confidence Interval (2-Sided) 95%
    -35.44 to 7.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 10.274
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.29
    Confidence Interval (2-Sided) 95%
    -33.39 to 18.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.369
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.24
    Confidence Interval (2-Sided) 95%
    -20.40 to 5.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.472
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 60.33
    Confidence Interval (2-Sided) 95%
    -10.78 to 131.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 34.455
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 59.87
    Confidence Interval (2-Sided) 95%
    -71.51 to 191.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 65.007
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 54.78
    Confidence Interval (2-Sided) 95%
    -27.09 to 136.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 40.440
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    27. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the safety population who have at least 1 diary entry of the relevant questionnaire data during the visit interval; n=number of participants with the given GI episode during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Nausea; n=10, 18, 18, 20
    10.47
    (18.678)
    7.23
    (10.916)
    11.18
    (19.568)
    2.86
    (3.359)
    Diarrhea; n=13, 20, 14, 14
    5.20
    (11.309)
    2.53
    (3.013)
    16.04
    (35.945)
    4.97
    (10.074)
    Upper abdominal pain; n=14, 14, 17, 15
    21.37
    (51.620)
    6.81
    (16.876)
    17.65
    (26.294)
    4.31
    (6.350)
    Lower abdominal pain; n=9, 18, 14, 13
    5.40
    (4.658)
    14.20
    (27.637)
    12.51
    (17.621)
    6.30
    (6.080)
    Vomiting; n=2, 2, 2, 2
    4.31
    (5.999)
    5.63
    (5.834)
    2.53
    (3.500)
    0.75
    (0.707)
    Indigestion; n=11, 11, 9, 11
    5.08
    (8.552)
    29.00
    (48.416)
    3.93
    (2.873)
    5.05
    (8.665)
    Constipation; n=4, 8, 11, 11
    17.05
    (7.452)
    27.61
    (35.177)
    15.12
    (7.761)
    21.28
    (19.298)
    Bloating; n=9, 14, 19, 11
    6.70
    (6.792)
    13.81
    (25.321)
    11.07
    (10.631)
    95.69
    (186.884)
    Flatulence; n=21, 17, 22, 19
    12.83
    (27.948)
    9.34
    (12.946)
    35.86
    (134.748)
    61.13
    (168.572)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.95
    Confidence Interval (2-Sided) 95%
    -6.79 to 14.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.281
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.37
    Confidence Interval (2-Sided) 95%
    -9.57 to 0.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.563
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 13.51
    Confidence Interval (2-Sided) 95%
    -2.84 to 29.86
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.024
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.44
    Confidence Interval (2-Sided) 95%
    -2.41 to 7.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.379
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.84
    Confidence Interval (2-Sided) 95%
    -5.81 to 27.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.143
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.50
    Confidence Interval (2-Sided) 95%
    -12.08 to 7.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.671
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.69
    Confidence Interval (2-Sided) 95%
    -19.03 to 15.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.488
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.91
    Confidence Interval (2-Sided) 95%
    -23.93 to 8.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.832
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.10
    Confidence Interval (2-Sided) 95%
    -23.80 to 17.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.811
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Vomiting
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.88
    Confidence Interval (2-Sided) 95%
    -22.75 to 13.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.155
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -25.08
    Confidence Interval (2-Sided) 95%
    -59.20 to 9.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 16.243
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -23.95
    Confidence Interval (2-Sided) 95%
    -54.89 to 6.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 14.830
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.49
    Confidence Interval (2-Sided) 95%
    -35.38 to 10.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 10.847
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.33
    Confidence Interval (2-Sided) 95%
    -32.79 to 20.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.542
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.73
    Confidence Interval (2-Sided) 95%
    -15.87 to 10.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.442
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 81.89
    Confidence Interval (2-Sided) 95%
    -22.04 to 185.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 50.239
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 26.52
    Confidence Interval (2-Sided) 95%
    -40.13 to 93.18
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 32.896
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 51.78
    Confidence Interval (2-Sided) 95%
    -31.65 to 135.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 41.055
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    28. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the safety population who have at least 1 diary entry of the relevant questionnaire data during the visit interval; n=number of participants with the given GI episode during the visit interval.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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 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.
    Measure Participants 44 43 43 42
    Nausea; n=4, 9, 6, 9
    3.96
    (3.668)
    4.34
    (6.256)
    2.66
    (1.390)
    2.34
    (1.904)
    Diarrhea; n=12, 13, 6, 8
    4.50
    (6.389)
    6.62
    (12.782)
    7.05
    (8.002)
    2.14
    (2.007)
    Upper abdominal pain; n=6, 5, 5, 5
    5.29
    (5.785)
    1.12
    (0.965)
    1.86
    (1.491)
    1.73
    (1.440)
    Lower abdominal pain; n=7, 5, 5, 9
    6.63
    (7.739)
    3.98
    (3.516)
    2.84
    (1.477)
    22.54
    (61.180)
    Vomiting; n=1, 1, 1, 0
    9.00
    (NA)
    19.00
    (NA)
    0.58
    (NA)
    NA
    (NA)
    Indigestion; n=6, 7, 7, 5
    2.43
    (1.569)
    2.57
    (2.586)
    5.02
    (6.944)
    1.63
    (1.101)
    Constipation; n=5, 2, 4, 4
    23.35
    (17.110)
    15.47
    (21.143)
    21.30
    (23.181)
    18.24
    (8.644)
    Bloating; n=7, 8, 7, 8
    12.49
    (10.595)
    18.52
    (25.682)
    4.16
    (3.018)
    85.64
    (115.872)
    Flatulence; n=9, 13, 7, 10
    44.67
    (112.426)
    7.21
    (10.051)
    105.86
    (275.125)
    18.48
    (26.347)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.68
    Confidence Interval (2-Sided) 95%
    -7.35 to 3.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.626
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Nausea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.00
    Confidence Interval (2-Sided) 95%
    -6.62 to 2.62
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.180
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.43
    Confidence Interval (2-Sided) 95%
    -11.64 to 12.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.717
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Diarrhea
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.48
    Confidence Interval (2-Sided) 95%
    -14.11 to 5.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.597
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    -1.10 to 2.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.794
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Upper abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.61
    Confidence Interval (2-Sided) 95%
    -1.17 to 2.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.775
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.14
    Confidence Interval (2-Sided) 95%
    -5.08 to 2.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.705
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Lower abdominal pain
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 18.56
    Confidence Interval (2-Sided) 95%
    -42.19 to 79.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 27.886
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.46
    Confidence Interval (2-Sided) 95%
    -3.65 to 8.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.801
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Indigestion
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.94
    Confidence Interval (2-Sided) 95%
    -3.71 to 1.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.242
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.83
    Confidence Interval (2-Sided) 95%
    -48.73 to 60.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 19.649
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Constipation
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.76
    Confidence Interval (2-Sided) 95%
    -28.38 to 33.91
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 11.219
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.36
    Confidence Interval (2-Sided) 95%
    -35.56 to 6.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.811
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Bloating
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 67.12
    Confidence Interval (2-Sided) 95%
    -22.88 to 157.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 41.961
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 + ASA
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 98.65
    Confidence Interval (2-Sided) 95%
    -58.01 to 255.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 74.566
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection BG00012, BG00012 Slow Titration
    Comments Flatulence
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.27
    Confidence Interval (2-Sided) 95%
    -5.22 to 27.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.928
    Estimation Comments Reference arm is BG00012 240 mg BID; negative values means reduced side effect.

    Adverse Events

    Time Frame AEs: from the administration of the first dose of study treatment to the Safety Follow-up (approximately 9 weeks). SAEs: from signing of informed consent to the Safety Follow-up (up to approximately 13 weeks).
    Adverse Event Reporting Description Flushing and GI events/symptoms captured separately in the eDiary were not recorded on the AE eCRF unless the events/symptoms led to discontinuation or withdrawal from the study, were classified as SAEs, or were ongoing at the final eDiary entry.
    Arm/Group Title Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Arm/Group Description 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 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.
    All Cause Mortality
    Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 1/43 (2.3%) 0/43 (0%) 0/42 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Ovarian germ cell teratoma stage I 0/44 (0%) 1/43 (2.3%) 0/43 (0%) 0/42 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo BG00012 BG00012 + ASA BG00012 Slow Titration
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/44 (11.4%) 12/43 (27.9%) 15/43 (34.9%) 12/42 (28.6%)
    Blood and lymphatic system disorders
    Eosinophilia 0/44 (0%) 1/43 (2.3%) 3/43 (7%) 2/42 (4.8%)
    Gastrointestinal disorders
    Abdominal pain 0/44 (0%) 0/43 (0%) 3/43 (7%) 0/42 (0%)
    Diarrhoea 0/44 (0%) 2/43 (4.7%) 5/43 (11.6%) 0/42 (0%)
    Vomiting 0/44 (0%) 2/43 (4.7%) 3/43 (7%) 0/42 (0%)
    Infections and infestations
    Upper respiratory tract infection 1/44 (2.3%) 3/43 (7%) 7/43 (16.3%) 1/42 (2.4%)
    Nervous system disorders
    Headache 4/44 (9.1%) 9/43 (20.9%) 2/43 (4.7%) 9/42 (21.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

    Results Point of Contact

    Name/Title Biogen Study Medical Director
    Organization Biogen
    Phone
    Email clinicaltrials@biogen.com
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT01568112
    Other Study ID Numbers:
    • 109HV321
    First Posted:
    Apr 2, 2012
    Last Update Posted:
    Jun 13, 2016
    Last Verified:
    May 1, 2016