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    Clinical Trial Results:
    CONFIDENCE: A Multinational, Multicenter, Randomized, Parallel Group, Open-Label Study to Assess Medication Satisfaction in Patients with Relapsing Remitting Multiple Sclerosis (RRMS) Treated with Subcutaneous Injections of Copaxone® (Glatiramer Acetate) 40 mg/mL Three Times a Week Compared to 20 mg/mL Daily

    Summary
    EudraCT number
    2015-000922-12
    Trial protocol
    BE   AT   DE   IE   PL   FI   ES   HR   FR   IT  
    Global end of trial date
    02 Jun 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Aug 2018
    First version publication date
    18 Aug 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    TV44400-CNS-40083
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02499900
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Teva Pharmaceutical Industries, Ltd.
    Sponsor organisation address
    12 Hatrufa St., P.O. Box 8077, Sapir Industrial Zone, Netanya, Israel, 42504
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 888-483-8279 , info.era-clinical@teva.de
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 888-483-8279 , info.era-clinical@teva.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jun 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to compare patient medication satisfaction as measured by the Medication Satisfaction Questionnaire (MSQ) scores between the Copaxone 40 mg/mL three times a week (TIW) group and the Copaxone 20 mg/mL once daily (QD) group over 6 months of treatment.
    Protection of trial subjects
    For adult subjects, written informed consent signed and dated by the subject before conducting any study-related procedures; for minor subjects, written informed consent signed and dated by the parent/legal guardian and written assent signed and dated by the subject before conducting any study related procedure.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Aug 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 142
    Country: Number of subjects enrolled
    Spain: 39
    Country: Number of subjects enrolled
    Croatia: 88
    Country: Number of subjects enrolled
    Austria: 30
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Finland: 5
    Country: Number of subjects enrolled
    France: 95
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 109
    Country: Number of subjects enrolled
    Argentina: 10
    Country: Number of subjects enrolled
    Mexico: 39
    Country: Number of subjects enrolled
    Puerto Rico: 4
    Country: Number of subjects enrolled
    Russian Federation: 198
    Country: Number of subjects enrolled
    Turkey: 22
    Country: Number of subjects enrolled
    United States: 61
    Worldwide total number of subjects
    861
    EEA total number of subjects
    527
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    846
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 876 patients with RRMS were screened for enrollment into this study. Of the 876 patients screened, 861 patients at 88 centers in Russian Federation, Poland, Italy, France, Croatia, US, Mexico, Spain, Austria, Turkey, Belgium, Argentina, Germany, Finland, & Puerto Rico met entry criteria and were considered to be eligible for enrollment.

    Pre-assignment
    Screening details
    Of the 15 patients who were not enrolled, 2 patients were excluded on the basis of inclusion criteria not met, 4 patients were excluded on the basis of exclusion criteria met, 7 patients withdrew consent, and 2 patients were lost to follow-up before the baseline visit.

    Period 1
    Period 1 title
    Core Study Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Copaxone® 20 mg/mL QD
    Arm description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Arm title
    Copaxone® 40 mg/mL TIW
    Arm description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Number of subjects in period 1
    Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
    Started
    430
    431
    Safety Analysis Set
    427
    430
    Completed
    395
    399
    Not completed
    35
    32
         Death
    -
    1
         Protocol deviation
    3
    -
         Adverse event
    18
    14
         Pregnancy
    1
    -
         Not specified
    1
    4
         Consent withdrawn by subject
    11
    10
         Per sponsor request
    -
    1
         Lost to follow-up
    1
    2
    Period 2
    Period 2 title
    Completed Core, Continued Into Extension
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Copaxone® 20 mg/mL QD
    Arm description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Arm title
    Copaxone® 40 mg/mL TIW
    Arm description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled injector
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Number of subjects in period 2
    Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
    Started
    395
    399
    Completed
    392
    397
    Not completed
    3
    2
         Did not wish to take injectable drugs
    1
    -
         Physician decision
    1
    -
         Personal motivation
    1
    -
         Consent withdrawn by subject
    -
    2
    Period 3
    Period 3 title
    Extension Study Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Copaxone® 20 mg/mL QD
    Arm description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Arm title
    Copaxone® 40 mg/mL TIW
    Arm description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Arm type
    Experimental

    Investigational medicinal product name
    Copaxone®
    Investigational medicinal product code
    Other name
    glatiramer acetate
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients administered Copaxone at home at the required frequency and according to the appropriate product instructions.

    Number of subjects in period 3
    Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
    Started
    392
    397
    Completed
    380
    377
    Not completed
    12
    20
         Physician decision
    2
    5
         Adverse event
    2
    4
         Pregnancy
    1
    2
         Not specified
    -
    2
         Consent withdrawn by subject
    5
    2
         Lost to follow-up
    2
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Copaxone® 20 mg/mL QD
    Reporting group description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Reporting group title
    Copaxone® 40 mg/mL TIW
    Reporting group description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Reporting group values
    Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW Total
    Number of subjects
    430 431 861
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    40.1 ± 10.67 41.0 ± 11.15 -
    Gender categorical
    Units: Subjects
        Female
    307 288 595
        Male
    123 143 266
    Race/Ethnicity, Customized
    Units: Subjects
        White
    363 359 722
        Black or African American
    4 3 7
        American Indian or Alaskan Native
    1 0 1
        Other
    59 63 122
        Missing
    3 6 9
    Weight
    n=425, 424; some subjects were missing a baseline weight.
    Units: kg
        arithmetic mean (standard deviation)
    70.49 ± 16.471 71.85 ± 16.265 -
    Body Mass Index (BMI)
    n=425, 424; due to the missing baseline weight assessments, BMI could not be calculated for those subjects.
    Units: kg/m^2
        arithmetic mean (standard deviation)
    24.62 ± 5.272 24.93 ± 4.879 -
    Height
    n=425, 425; some subjects were missing baseline height data.
    Units: cm
        arithmetic mean (standard deviation)
    168.6 ± 9.24 169.4 ± 8.56 -

    End points

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    End points reporting groups
    Reporting group title
    Copaxone® 20 mg/mL QD
    Reporting group description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Reporting group title
    Copaxone® 40 mg/mL TIW
    Reporting group description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Reporting group title
    Copaxone® 20 mg/mL QD
    Reporting group description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Reporting group title
    Copaxone® 40 mg/mL TIW
    Reporting group description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.
    Reporting group title
    Copaxone® 20 mg/mL QD
    Reporting group description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Reporting group title
    Copaxone® 40 mg/mL TIW
    Reporting group description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12.

    Subject analysis set title
    Full Analysis Set: Copaxone® 20 mg/mL QD
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subcutaneous injections of 20 mg/mL QD for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12. The full analysis set included those patients in the intention to treat (ITT) analysis set [all randomized subjects] who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment.

    Subject analysis set title
    Full Analysis Set: Copaxone® 40 mg/mL TIW
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subcutaneous injections of 40 mg/mL TIW for the core period, which lasted 6 months. In the extension period, patients were administered Copaxone® 40 mg/mL for Months 7 - 12. The full analysis set included those patients in the ITT analysis set [all randomized subjects] who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment.

    Subject analysis set title
    Safety Analysis Set: Copaxone® 20 mg/mL QD (Core)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subcutaneous injections of Copaxone 20 mg/mL QD for the core period from Day 1 to Month 6. The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Subject analysis set title
    Safety Analysis Set: Copaxone® 40 mg/mL TIW (Core)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subcutaneous injections of Copaxone 40 mg/mL TIW for the core period from Day 1 to Month 6. The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Subject analysis set title
    Safety Analysis Set:Copaxone® 40 mg/mL TIW (Switch- Extension)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subjects who were administered daily Copaxone 20 mg/mL daily injections during the core period, and were switched to 40 mg/mL TIW injections for the extension period (Months 7-12). The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Subject analysis set title
    Safety Analysis Set: Copaxone® 40 mg/mL TIW (Extension)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subjects who were administered Copaxone 40 mg/mL TIW injections during the core period, and continued Copaxone at that same dosage for the extension period (Months 7-12). The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Primary: Change From Baseline in the MSQ to Month 6 Using a Repeated Measures Analysis of Covariance (ANCOVA)

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    End point title
    Change From Baseline in the MSQ to Month 6 Using a Repeated Measures Analysis of Covariance (ANCOVA)
    End point description
    Patient satisfaction with the study medication was assessed using the MSQ, a 1-item, global, patient-rated scale. Patients were asked to respond on a 7-point scale, ranging from extremely dissatisfied (1) to extremely satisfied (7), to the following: “Overall, how satisfied are you with your current medication?”. Positive change from baseline score indicates greater satisfaction with the medication. Estimates and p-value are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: MSQ=baseline MSQ score+treatment+visit+treatment by visit interaction.
    End point type
    Primary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    221 [1]
    235 [2]
    Units: units on a scale
        least squares mean (standard error)
    5.396 ± 0.0889
    5.717 ± 0.0879
    Notes
    [1] - Treatment naïve patients do not have a MSQ score at baseline so are not included.
    [2] - Treatment naïve patients do not have a MSQ score at baseline so are not included.
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Estimates and p-value are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: MSQ=baseline MSQ core+treatment+visit+treatment by visit interaction. Treatment-naïve patients are not included in this analysis as MSQ is not measured at baseline for these patients.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    456
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [3]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.321
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.1615
         upper limit
    0.4814
    Notes
    [3] - 0.05 level of significance

    Secondary: Change From Baseline in the Treatment Satisfaction Questionnaire for Medication 9-item Version (TSQM-9) Convenience Score to Month 6 Using a Repeated Measures ANCOVA

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    End point title
    Change From Baseline in the Treatment Satisfaction Questionnaire for Medication 9-item Version (TSQM-9) Convenience Score to Month 6 Using a Repeated Measures ANCOVA
    End point description
    Convenience perception was measured by the 3 convenience items (items 4 to 6) within the validated TSQM-9. The responses to each of the 3 convenience items are reported on a 1-to-7 scale. The TSQM-9 convenience scale is computed, for each subject, by adding the 3 items loading on each response with the lowest possible total score (1*3 on the 3 items) subtracted from this composite score, and divided by the greatest possible score (3*7) minus the lowest possible score (3), i.e., 21-3=18. This provides a transformed score between 0 and 1 that was multiplied by 100. The final scale is 0 (Extremely Difficult/Inconvenient) to 100 (Extremely Easy/Convenient). If more than one item is missing, then the convenience scale was considered invalid for that patient. Estimates and p-value are obtained from baseline-adjusted repeated measures ANCOVA with treatment, visit, and Country/Geographical Region as main factors, visit by treatment as the interaction term, and baseline score as the covariate.
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    216 [4]
    223 [5]
    Units: units on a scale
        least squares mean (standard error)
    69.740 ± 1.1999
    79.189 ± 1.2347
    Notes
    [4] - Treatment naïve patients do not have TSQM-9 convenience scores at baseline and are not included.
    [5] - Treatment naïve patients do not have TSQM-9 convenience scores at baseline and are not included.
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Estimates and p-value are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: TSQM-9 convenience score=baseline TSQM-9 convenience score+treatment+CGR+treatment by visit interaction. Treatment-naïve patients are not included in this analysis as TSQM-9 is not measured at baseline for these patients.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    439
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [6]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    9.448
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.9538
         upper limit
    11.9429
    Notes
    [6] - 0.05 level of significance

    Secondary: Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA

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    End point title
    Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA
    End point description
    MFIS is a modified form of the Fatigue Impact Scale based on items derived from interviews with MS patients concerning how fatigue impacts their lives. It is a structured, self-report questionnaire consisting of 21 items assessing the effects of fatigue. All 21 items are scaled 0 to 4, with higher scores indicating a greater impact of fatigue on patient's activities. The Total MFIS score ranges from 0 to 84, the Physical Subscale from 0 to 36, the Cognitive Subscale from 0 to 40, and the Psychosocial Subscale from 0 to 8. A score of 0 indicates fatigue has no impact on activities and the high-end score indicates fatigue has extreme impact on activities. Negative change from baseline values indicate improvement in the effects of fatigue. Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MFIS score=baseline MFIS score+treatment+visit +Country/Geographical Region+treatment by visit interaction.
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    422 [7]
    425 [8]
    Units: units on a scale
    least squares mean (standard error)
        MFIS Total Score
    -2.811 ± 0.5166
    -3.613 ± 0.5052
        MFIS Physical Subscale
    -1.483 ± 0.2599
    -1.714 ± 0.2535
        MFIS Cognitive Subscale
    -0.965 ± 0.2553
    -1.604 ± 0.2503
        MFIS Psychosocial Subscale
    -0.306 ± 0.0704
    -0.204 ± 0.0685
    Notes
    [7] - The subject was considered invalid for MFIS if any of the items were missing.
    [8] - The subject was considered invalid for MFIS if any of the items were missing.
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    MFIS Total Score Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MFIS score=baseline MFIS score+treatment+visit +country/geographical region (CGR)+treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    847
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.208 [9]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.802
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.05
         upper limit
    0.4461
    Notes
    [9] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    MFIS Physical Subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MFIS score=baseline MFIS score+treatment+visit +CGR+treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 40 mg/mL TIW v Full Analysis Set: Copaxone® 20 mg/mL QD
    Number of subjects included in analysis
    847
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.47 [10]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.231
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8588
         upper limit
    0.3962
    Notes
    [10] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    MFIS Cognitive Subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MFIS score=baseline MFIS score+treatment+visit +CGR+treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    847
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.043 [11]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.639
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2564
         upper limit
    -0.0214
    Notes
    [11] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    MFIS Psychosocial Subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MFIS score=baseline MFIS score+treatment+visit +CGR+treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    847
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.237 [12]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.102
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.0672
         upper limit
    0.2711
    Notes
    [12] - 0.05 level of significance

    Secondary: Change From Baseline in the Mental Health Index (MHI) Total Score and Anxiety and Depression Subscales to Month 6 Using a Repeated Measures ANCOVA

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    End point title
    Change From Baseline in the Mental Health Index (MHI) Total Score and Anxiety and Depression Subscales to Month 6 Using a Repeated Measures ANCOVA
    End point description
    The MHI consists of 18 items and provides an assessment of 4 subscales of mental health, including Anxiety (5 items), Depression (4 items), Behavioral Control (4 items), and Positive Affect (4 items), and 1 Total Score. The subscales and Total Score for analyses range from 0 to 100 each, with 0 indicating not mentally healthy and 100 indicating superior mental health. Positive change from baseline scores indicate improved mental health. Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction. If a participant skipped x items of y items, the scale was not computed: MHI Total Score, 9 of 19; Anxiety subscale, 2 of 5; Depression subscale, 2 of 4; Behavioral Control subscale, 2 of 4; MHI Positive Affect subscale, 2 of 4.
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    422 [13]
    426 [14]
    Units: units on a scale
    least squares mean (standard deviation)
        MHI Total Score
    3.136 ± 0.5381
    3.842 ± 0.5249
        Anxiety subscale
    5.468 ± 0.6861
    5.609 ± 0.6695
        Depression subscale
    3.773 ± 0.6433
    4.253 ± 0.6270
    Notes
    [13] - subjects with an assessment
    [14] - subjects with an assessment
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Total Score Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    848
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.287 [15]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.706
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5947
         upper limit
    1.0074
    Notes
    [15] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Anxiety subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    848
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.868 [16]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.141
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5179
         upper limit
    1.7991
    Notes
    [16] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Depression subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI depression subscale=baseline MHI depression subscale+treatment+visit+CGR+treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    848
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.544 [17]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.481
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.0734
         upper limit
    2.0348
    Notes
    [17] - 0.05 level of significance

    Secondary: Change From Baseline in the MHI Behavioral Control and Positive Affect Subscales to Month 6 Using a Repeated Measures ANCOVA

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    End point title
    Change From Baseline in the MHI Behavioral Control and Positive Affect Subscales to Month 6 Using a Repeated Measures ANCOVA
    End point description
    The MHI consists of 18 items and provides an assessment of 4 subscales of mental health, including Anxiety (5 items), Depression (4 items), Behavioral Control (4 items), and Positive Affect (4 items), and 1 Total Score. The subscales and Total Score for analyses range from 0 to 100 each, with 0 indicating not mentally healthy and 100 indicating superior mental health. Positive change from baseline scores indicate improved mental health. Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction. If a participant skipped x items of y items, the scale was not computed: MHI Total Score, 9 of 19; Anxiety subscale, 2 of 5; Depression subscale, 2 of 4; Behavioral Control subscale, 2 of 4; MHI Positive Affect subscale, 2 of 4.
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    423 [18]
    426 [19]
    Units: units on a scale
    least squares mean (standard error)
        Behavioral Control
    0.659 ± 0.6133
    2.526 ± 0.6000
        MHI Positive Affect
    3.024 ± 0.7306
    2.932 ± 0.7126
    Notes
    [18] - subjects with an assessment
    [19] - subjects with an assessment
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Behavioral Control subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    849
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014 [20]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.867
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3843
         upper limit
    3.3487
    Notes
    [20] - 0.05 level of significance
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Behavioral Control subscale Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline MHI score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    849
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.919 [21]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.092
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8565
         upper limit
    1.6728
    Notes
    [21] - 0.05 level of significance

    Secondary: Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA

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    End point title
    Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA
    End point description
    Depressive symptoms were measured by the BDI-II, a 21-item, self-reported rating inventory that measures characteristic attitudes and symptoms of depression. The BDI-II assesses mood, pessimism, sense of failure, self dissatisfaction, guilt, punishment, self-dislike, self-accusation, suicidal ideas, sadness, crying, irritability, social withdrawal, body image, work difficulties, insomnia, fatigue, appetite, weight loss, bodily preoccupation, and loss of libido. Each of the 21 items is rated on a 4-point scale ranging from 0 to 3. BDI-II Total Score indicates the severity of depression and has a total range of 0 to 63. For those clinically diagnosed, scores from 0-13 represent minimal depressive symptoms, scores of 14-19 indicate mild depression, scores of 20-28 indicate moderate depression, and scores of 30-63 indicate severe depression. Negative change from baseline scores indicate improvement.
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0), Months 1, 3 and 6
    End point values
    Full Analysis Set: Copaxone® 20 mg/mL QD Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects analysed
    422 [22]
    426 [23]
    Units: units on a scale
        least squares mean (standard error)
    -1.525 ± 0.2560
    -1.585 ± 0.2495
    Notes
    [22] - subjects with an assessment
    [23] - subjects with an assessment
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Estimates and p-values are obtained from baseline-adjusted repeated measures ANCOVA model with visit as a repeated effect: change from baseline BDI-II total score=baseline BDIII total score+treatment+visit+country/geographic region +treatment by visit interaction.
    Comparison groups
    Full Analysis Set: Copaxone® 20 mg/mL QD v Full Analysis Set: Copaxone® 40 mg/mL TIW
    Number of subjects included in analysis
    848
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.851 [24]
    Method
    Repeated Measures ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.059
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6777
         upper limit
    0.5592
    Notes
    [24] - 0.05 level of significance

    Secondary: Subjects With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods

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    End point title
    Subjects With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods
    End point description
    An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. The investigator determined relation to study drug. A severe AE is defined as an inability to carry out usual activities. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories.
    End point type
    Secondary
    End point timeframe
    Core: Day 1 to Month 6; Extension: Month 7 to Month 12
    End point values
    Safety Analysis Set: Copaxone® 20 mg/mL QD (Core) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Core) Safety Analysis Set:Copaxone® 40 mg/mL TIW (Switch- Extension) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Extension)
    Number of subjects analysed
    427
    430
    392
    396
    Units: subjects
        >= 1 TEAE
    219
    231
    132
    129
        >= 1 serious TEAE
    8
    13
    3
    2
        >= 1 serious fatal TEAE
    0
    0
    0
    0
        >= 1 serious and related TEAE
    1
    2
    0
    0
        >= 1 Severe TEAE
    4
    3
    1
    0
        >= 1 injection-related TEAE
    149
    146
    38
    25
        >=1 TEAE leading to withdrawal
    18
    13
    2
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Core study period: Day 1 to Month 6; Extension study period: Month 7 to Month 12
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Safety Analysis Set: Copaxone® 20 mg/mL QD (Core)
    Reporting group description
    Subcutaneous injections of Copaxone 20 mg/mL QD for the core period from Day 1 to Month 6. The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Reporting group title
    Safety Analysis Set: Copaxone® 40 mg/mL TIW (Core)
    Reporting group description
    Subcutaneous injections of Copaxone 40 mg/mL TIW for the core period from Day 1 to Month 6. The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Reporting group title
    Safety Analysis Set:Copaxone® 40 mg/mL TIW (Switch- Extension)
    Reporting group description
    Subjects who were administered daily Copaxone 20 mg/mL daily injections during the core period, and were switched to 40 mg/mL TIW injections for the extension period (Months 7-12). The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Reporting group title
    Safety Analysis Set: Copaxone® 40 mg/mL TIW (Extension)
    Reporting group description
    Subjects who were administered Copaxone 40 mg/mL TIW injections during the core period, and continued Copaxone at that same dosage for the extension period (Months 7-12). The Safety Analysis Set included all randomized patients who received at least 1 dose of Copaxone, based on the treatment patients actually received regardless of the treatment to which they were randomized.

    Serious adverse events
    Safety Analysis Set: Copaxone® 20 mg/mL QD (Core) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Core) Safety Analysis Set:Copaxone® 40 mg/mL TIW (Switch- Extension) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Extension)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 427 (1.87%)
    13 / 430 (3.02%)
    3 / 392 (0.77%)
    2 / 396 (0.51%)
         number of deaths (all causes)
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 427 (0.00%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiomyopathy
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 427 (0.00%)
    0 / 430 (0.00%)
    1 / 392 (0.26%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Sciatica
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    1 / 392 (0.26%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 427 (0.00%)
    2 / 430 (0.47%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    1 / 392 (0.26%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Pituitary hyperplasia
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    1 / 427 (0.23%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    0 / 392 (0.00%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 427 (0.00%)
    1 / 430 (0.23%)
    1 / 392 (0.26%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 427 (0.00%)
    0 / 430 (0.00%)
    0 / 392 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Safety Analysis Set: Copaxone® 20 mg/mL QD (Core) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Core) Safety Analysis Set:Copaxone® 40 mg/mL TIW (Switch- Extension) Safety Analysis Set: Copaxone® 40 mg/mL TIW (Extension)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    121 / 427 (28.34%)
    117 / 430 (27.21%)
    22 / 392 (5.61%)
    15 / 396 (3.79%)
    General disorders and administration site conditions
    Injection site swelling
         subjects affected / exposed
    34 / 427 (7.96%)
    32 / 430 (7.44%)
    1 / 392 (0.26%)
    1 / 396 (0.25%)
         occurrences all number
    34
    32
    1
    1
    Injection site pain
         subjects affected / exposed
    84 / 427 (19.67%)
    89 / 430 (20.70%)
    10 / 392 (2.55%)
    5 / 396 (1.26%)
         occurrences all number
    92
    109
    11
    6
    Injection site erythema
         subjects affected / exposed
    71 / 427 (16.63%)
    61 / 430 (14.19%)
    10 / 392 (2.55%)
    4 / 396 (1.01%)
         occurrences all number
    75
    65
    10
    4
    Injection site pruritus
         subjects affected / exposed
    58 / 427 (13.58%)
    37 / 430 (8.60%)
    5 / 392 (1.28%)
    4 / 396 (1.01%)
         occurrences all number
    61
    40
    5
    4
    Injection site bruising
         subjects affected / exposed
    24 / 427 (5.62%)
    17 / 430 (3.95%)
    5 / 392 (1.28%)
    4 / 396 (1.01%)
         occurrences all number
    24
    17
    5
    4
    Injection site haemorrhage
         subjects affected / exposed
    20 / 427 (4.68%)
    22 / 430 (5.12%)
    2 / 392 (0.51%)
    3 / 396 (0.76%)
         occurrences all number
    23
    26
    2
    3

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Sep 2015
    The primary reason for this amendment was to revise inclusion criterion (e) regarding birth control methods, in accordance with the Clinical Trial Facilitation Group “Recommendations related to contraception and pregnancy testing in clinical trials” (dated 15 September 2014).

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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