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Study to Assess Medication Satisfaction in Patients With Relapsing Remitting Multiple Sclerosis Treated With Copaxone® (CONFIDENCE)

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ClinicalTrials.gov Identifier: NCT02499900
Recruitment Status : Completed
First Posted : July 16, 2015
Results First Posted : August 20, 2018
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Pharmaceutical Industries, Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Drug: Copaxone®
Enrollment 861
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 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.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12. Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Period Title: Core Study Period
Started [1] 430 431
Safety Analysis Set 427 430
Completed [2] 395 399
Not Completed 35 32
Reason Not Completed
Not specified             1             4
Lost to Follow-up             1             2
Per sponsor request             0             1
Pregnancy             1             0
Protocol Violation             3             0
Withdrawal by Subject             11             10
Adverse Event             18             14
Death             0             1
[1]
Intent to treat
[2]
Completed core phase of the study
Period Title: Completed Core, Continued Into Extension
Started 395 399
Completed 392 397
Not Completed 3 2
Reason Not Completed
Physician Decision             1             0
Withdrawal by Subject             0             2
Did not wish to take injectables drugs             1             0
Personal motivation             1             0
Period Title: Extension Study Period
Started 392 397
Safety Analysis Set 392 396 [1]
Completed 380 377
Not Completed 12 20
Reason Not Completed
Adverse Event             2             4
Withdrawal by Subject             5             2
Physician Decision             2             5
Pregnancy             1             2
Lost to Follow-up             2             5
Not specified             0             2
[1]
One participant was not treated in the Extension Study Period
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW Total
Hide Arm/Group Description Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12. Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12. Total of all reporting groups
Overall Number of Baseline Participants 430 431 861
Hide Baseline Analysis Population Description
ITT Analysis Set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 430 participants 431 participants 861 participants
40.1  (10.67) 41.0  (11.15) 40.5  (10.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 430 participants 431 participants 861 participants
Female
307
  71.4%
288
  66.8%
595
  69.1%
Male
123
  28.6%
143
  33.2%
266
  30.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 430 participants 431 participants 861 participants
White
363
  84.4%
359
  83.3%
722
  83.9%
Black or African American
4
   0.9%
3
   0.7%
7
   0.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaskan Native
1
   0.2%
0
   0.0%
1
   0.1%
Native Hawaiian or Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
59
  13.7%
63
  14.6%
122
  14.2%
Missing
3
   0.7%
6
   1.4%
9
   1.0%
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 425 participants 424 participants 849 participants
70.49  (16.471) 71.85  (16.265) 71.17  (16.373)
[1]
Measure Analysis Population Description: Some participants were missing a baseline weight
Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 425 participants 424 participants 849 participants
24.62  (5.272) 24.93  (4.879) 24.78  (5.079)
[1]
Measure Analysis Population Description: Due to the missing baseline weight assessments, BMI could not be calculated for those participants.
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 425 participants 425 participants 850 participants
168.6  (9.24) 169.4  (8.56) 169.0  (8.91)
[1]
Measure Analysis Population Description: Some participants were missing baseline height data.
1.Primary Outcome
Title Change From Baseline in the Medication Satisfaction Questionnaire (MSQ) to Month 6 Using a Repeated Measures ANCOVA
Hide 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.
Time Frame Baseline (Month 0), Months 1, 3 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included those patients in the intent to treat (ITT) analysis set who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment. Treatment naïve patients do not have a MSQ score at baseline so are not included.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description:
Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Overall Number of Participants Analyzed 221 235
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
5.396  (0.0889) 5.717  (0.0879)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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. Treatment-naïve patients are not included in this analysis as MSQ is not measured at baseline for these patients.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.321
Confidence Interval (2-Sided) 95%
0.1615 to 0.4814
Estimation Comments [Not Specified]
2.Secondary Outcome
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
Hide 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.
Time Frame Baseline (Month 0), Months 1, 3 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included those patients in the intent to treat (ITT) analysis set who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment. Treatment naïve patients do not have TSQM-9 convenience scores at baseline and therefore are not included.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description:
Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Overall Number of Participants Analyzed 216 223
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
69.740  (1.1999) 79.189  (1.2347)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.448
Confidence Interval (2-Sided) 95%
6.9538 to 11.9429
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA
Hide 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
Time Frame Baseline (Month 0), Months 1, 3 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). The participant was considered invalid if any of the items were missing.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description:
Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Overall Number of Participants Analyzed 427 428
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
MFIS Total Score Number Analyzed 422 participants 425 participants
-2.811  (0.5166) -3.613  (0.5052)
MFIS Physical Subscale Number Analyzed 422 participants 425 participants
-1.483  (0.2599) -1.714  (0.2535)
MFIS Cognitive Subscale Number Analyzed 422 participants 425 participants
-0.965  (0.2553) -1.604  (0.2503)
MFIS Psychosocial Subscale Number Analyzed 422 participants 425 participants
-0.306  (0.0704) -0.204  (0.0685)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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 +CGR+treatment by visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.208
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.802
Confidence Interval (2-Sided) 95%
-2.0500 to 0.4461
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.470
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.231
Confidence Interval (2-Sided) 95%
-0.8588 to 0.3962
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.639
Confidence Interval (2-Sided) 95%
-1.2564 to -0.0214
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.237
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.102
Confidence Interval (2-Sided) 95%
-0.0672 to 0.2711
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA
Hide 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, 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
Time Frame Baseline (Month 0), Months 1, 3 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description:
Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Overall Number of Participants Analyzed 427 428
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
MHI Total Score Number Analyzed 427 participants 428 participants
3.136  (0.5381) 3.842  (0.5249)
Anxiety subscale Number Analyzed 427 participants 428 participants
5.468  (0.6861) 5.609  (0.6695)
Depression subscale Number Analyzed 427 participants 428 participants
3.773  (0.6433) 4.253  (0.6270)
Behavioral Control subscale Number Analyzed 423 participants 428 participants
0.659  (0.6133) 2.526  (0.6000)
MHI Positive Affect subscale Number Analyzed 423 participants 428 participants
3.024  (0.7306) 2.932  (0.7126)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.287
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.706
Confidence Interval (2-Sided) 95%
-0.5947 to 1.0074
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.868
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.141
Confidence Interval (2-Sided) 95%
-1.5179 to 1.7991
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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 score=baseline MHI Total Score +treatment +visit +country/geographic region +treatment by visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.544
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.481
Confidence Interval (2-Sided) 95%
-1.0734 to 2.0348
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.867
Confidence Interval (2-Sided) 95%
0.3843 to 3.3487
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments MHI Positive Affect 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.919
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.092
Confidence Interval (2-Sided) 95%
-1.8565 to 1.6728
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA
Hide 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.
Time Frame Baseline (Month 0), Months 1, 3 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Copaxone® 20 mg/mL QD Copaxone® 40 mg/mL TIW
Hide Arm/Group Description:
Subcutaneous Injections 20 mg/mL daily (QD) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Subcutaneous Injections 40 mg/mL three times a week (TIW) for the core period which last 6 months. In the extension period patient are administered Copaxone® 40 mg/mL for months 7 - 12.
Overall Number of Participants Analyzed 422 426
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.525  (0.2560) -1.585  (0.2495)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Copaxone® 20 mg/mL QD, Copaxone® 40 mg/mL TIW
Comments 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 BDI-II total score+treatment+visit+country/geographic region +treatment by visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.851
Comments 0.05 level of significance
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.059
Confidence Interval (2-Sided) 95%
-0.6777 to 0.5592
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods
Hide 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.
Time Frame Core: Day 1 to Month 6 Extension: Month 7 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Copaxone® 20 mg/mL QD (Core) Copaxone® 40 mg/mL TIW (Core) Copaxone® 40 mg/mL TIW (Switch-Extension) Copaxone® 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Subcutaneous injections of Copaxone 20 mg/mL daily (QD) for the core period from Day 1 to Month 6.
Subcutaneous injections of Copaxone 40 mg/mL three times a week (TIW) for the core period from Day 1 to Month 6.
Participants who were administered daily Copaxone 20 mg/mL daily injections during the core period, were switched to 40 mg/mL three times a week (TIW) injections for the extension period (Months 7-12)
Participants who were administered Copaxone 40 mg/mL three times a week (TIW) injections during the core period, continued Copaxone at that same dosage for the extension period (Months 7-12)
Overall Number of Participants Analyzed 427 430 392 396
Measure Type: Count of Participants
Unit of Measure: Participants
>=1 TEAE
219
  51.3%
231
  53.7%
132
  33.7%
129
  32.6%
>= 1 serious TEAE
8
   1.9%
13
   3.0%
3
   0.8%
2
   0.5%
>=1 serious fatal TEAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=1 serious and related TEAE
1
   0.2%
2
   0.5%
0
   0.0%
0
   0.0%
>=1 Severe TEAE
4
   0.9%
3
   0.7%
1
   0.3%
0
   0.0%
>=1 injection-related TEAE
149
  34.9%
146
  34.0%
38
   9.7%
25
   6.3%
>=1 TEAE leading to withdrawal
18
   4.2%
13
   3.0%
2
   0.5%
3
   0.8%
Time Frame - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Copaxone® 20 mg/mL QD (Core) Copaxone® 40 mg/mL TIW (Core) Copaxone® 40 mg/mL TIW (Switch-Extension) Copaxone® 40 mg/mL TIW (Extension)
Hide Arm/Group Description Subcutaneous injections of Copaxone 20 mg/mL daily (QD) for the core period from Day 1 to Month 6. Subcutaneous injections of Copaxone 40 mg/mL three times a week (TIW) for the core period from Day 1 to Month 6. Participants who were administered daily Copaxone 20 mg/mL daily injections during the core period, were switched to 40 mg/mL three times a week (TIW) injections for the extension period (Months 7-12) Participants who were administered Copaxone 40 mg/mL three times a week (TIW) injections during the core period, continued Copaxone at that same dosage for the extension period (Months 7-12)
All-Cause Mortality
Copaxone® 20 mg/mL QD (Core) Copaxone® 40 mg/mL TIW (Core) Copaxone® 40 mg/mL TIW (Switch-Extension) Copaxone® 40 mg/mL TIW (Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/427 (0.00%)      1/430 (0.23%)      0/392 (0.00%)      0/396 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Copaxone® 20 mg/mL QD (Core) Copaxone® 40 mg/mL TIW (Core) Copaxone® 40 mg/mL TIW (Switch-Extension) Copaxone® 40 mg/mL TIW (Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/427 (1.87%)      13/430 (3.02%)      3/392 (0.77%)      2/396 (0.51%)    
Blood and lymphatic system disorders         
Leukocytosis  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Cardiac disorders         
Atrial fibrillation  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Cardiomyopathy  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Coronary artery disease  1  0/427 (0.00%)  0 0/430 (0.00%)  0 1/392 (0.26%)  1 0/396 (0.00%)  0
Endocrine disorders         
Pituitary hyperplasia  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Infections and infestations         
Erysipelas  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Escherichia sepsis  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Pneumonia  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Pyelonephritis  1  0/427 (0.00%)  0 0/430 (0.00%)  0 0/392 (0.00%)  0 1/396 (0.25%)  1
Urinary tract infection  1  0/427 (0.00%)  0 1/430 (0.23%)  1 1/392 (0.26%)  1 0/396 (0.00%)  0
Injury, poisoning and procedural complications         
Clavicle fracture  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Fall  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Intentional overdose  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Joint dislocation  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Rib fracture  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Scapula fracture  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthropathy  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Intervertebral disc protrusion  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Brain neoplasm  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Malignant melanoma  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Uterine leiomyoma  1  0/427 (0.00%)  0 0/430 (0.00%)  0 0/392 (0.00%)  0 1/396 (0.25%)  1
Nervous system disorders         
Multiple sclerosis  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Multiple sclerosis relapse  1  0/427 (0.00%)  0 1/430 (0.23%)  1 1/392 (0.26%)  1 0/396 (0.00%)  0
Sciatica  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Psychiatric disorders         
Depression  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Suicide attempt  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury  1  0/427 (0.00%)  0 2/430 (0.47%)  2 0/392 (0.00%)  0 0/396 (0.00%)  0
Nephrolithiasis  1  1/427 (0.23%)  1 0/430 (0.00%)  0 1/392 (0.26%)  1 0/396 (0.00%)  0
Urinary tract obstruction  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Reproductive system and breast disorders         
Dysfunctional uterine bleeding  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Uterine polyp  1  1/427 (0.23%)  1 0/430 (0.00%)  0 0/392 (0.00%)  0 0/396 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pneumothorax  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
Pulmonary oedema  1  0/427 (0.00%)  0 1/430 (0.23%)  1 0/392 (0.00%)  0 0/396 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Copaxone® 20 mg/mL QD (Core) Copaxone® 40 mg/mL TIW (Core) Copaxone® 40 mg/mL TIW (Switch-Extension) Copaxone® 40 mg/mL TIW (Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   121/427 (28.34%)      117/430 (27.21%)      22/392 (5.61%)      15/396 (3.79%)    
General disorders         
Injection site bruising  1  24/427 (5.62%)  24 17/430 (3.95%)  17 5/392 (1.28%)  5 4/396 (1.01%)  4
Injection site erythema  1  71/427 (16.63%)  75 61/430 (14.19%)  65 10/392 (2.55%)  10 4/396 (1.01%)  4
Injection site haemorrhage  1  20/427 (4.68%)  23 22/430 (5.12%)  26 2/392 (0.51%)  2 3/396 (0.76%)  3
Injection site pain  1  84/427 (19.67%)  92 89/430 (20.70%)  109 10/392 (2.55%)  11 5/396 (1.26%)  6
Injection site pruritus  1  58/427 (13.58%)  61 37/430 (8.60%)  40 5/392 (1.28%)  5 4/396 (1.01%)  4
Injection site swelling  1  34/427 (7.96%)  34 32/430 (7.44%)  32 1/392 (0.26%)  1 1/396 (0.25%)  1
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
This study's ‘interim’ CSR covered the Core Period and used a cut-off date. The ‘final’ CSR covered the entire study. AE counts as reported here reflect the entire database and show minor differences from the interim CSR due to the cut-off date.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Pharmaceutical Industries Ltd.
Phone: +01 215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Teva Pharmaceutical Industries, Ltd. )
ClinicalTrials.gov Identifier: NCT02499900     History of Changes
Other Study ID Numbers: TV44400-CNS-40083
2015-000922-12 ( EudraCT Number )
First Submitted: July 1, 2015
First Posted: July 16, 2015
Results First Submitted: July 17, 2018
Results First Posted: August 20, 2018
Last Update Posted: October 16, 2018