Multiple Sclerosis
Conditions
Brief summary
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 time a week (TIW) group and the Copaxone 20 mg/mL once daily (QD) group over 6 months of treatment.
Interventions
DRUGCopaxone®
Subcutaneous Injections
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women at least 18 years of age or older. 2. Patients must have a confirmed and documented RRMS diagnosis 3. Patients must be ambulatory with a Kurtzke EDSS score of 0 to 5.5 at screening visit. 4. Patients must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment 30 days prior to randomization. 5. Women of child-bearing potential must have a negative urine pregnancy test at screening visit and must practice an acceptable method of birth 6. Patients must be able to sign and date a written informed consent prior to entering the study. 7. Patients must be willing and able to comply with the protocol requirements for the duration of the study.
Exclusion criteria
1. Patient had any contraindication to Copaxone therapy. 2. Previous use of Copaxone 40 mg/mL three times per week. 3. Patients with progressive forms of MS. 4. Patients with neuromyelitis optica. 5. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening. 6. Patients who have been treated with; immunosuppressive medications, immunoglobulins and/or monoclonal antibodies, alemtuzumab, cladribine, cyclophosphamide or mitoxantrone at any time 7. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit. 8. Pregnancy or breastfeeding. 9. Clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation 10. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals * other criteria may apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Medication Satisfaction Questionnaire (MSQ) to Month 6 Using a Repeated Measures ANCOVA | Baseline (Month 0), Months 1, 3 and 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Month 0), Months 1, 3 and 6 | 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. |
| Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Baseline (Month 0), Months 1, 3 and 6 | 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 |
| Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Baseline (Month 0), Months 1, 3 and 6 | 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 |
| Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA | Baseline (Month 0), Months 1, 3 and 6 | 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. |
| Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | Core: Day 1 to Month 6 Extension: Month 7 to Month 12 | 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. |
Countries
Argentina, Austria, Belgium, Croatia, Finland, France, Germany, Ireland, Italy, Mexico, Poland, Puerto Rico, Russia, Spain, Turkey (Türkiye), United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Copaxone® 20 mg/mL QD 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. | 430 |
| Copaxone® 40 mg/mL TIW 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. | 431 |
| Total | 861 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Core, Continued Into Extension | Did not wish to take injectables drugs | 1 | 0 |
| Completed Core, Continued Into Extension | Personal motivation | 1 | 0 |
| Completed Core, Continued Into Extension | Physician Decision | 1 | 0 |
| Completed Core, Continued Into Extension | Withdrawal by Subject | 0 | 2 |
| Core Study Period | Adverse Event | 18 | 14 |
| Core Study Period | Death | 0 | 1 |
| Core Study Period | Lost to Follow-up | 1 | 2 |
| Core Study Period | Other | 1 | 4 |
| Core Study Period | Per sponsor request | 0 | 1 |
| Core Study Period | Pregnancy | 1 | 0 |
| Core Study Period | Protocol Violation | 3 | 0 |
| Core Study Period | Withdrawal by Subject | 11 | 10 |
| Extension Study Period | Adverse Event | 2 | 4 |
| Extension Study Period | Lost to Follow-up | 2 | 5 |
| Extension Study Period | Other | 0 | 2 |
| Extension Study Period | Physician Decision | 2 | 5 |
| Extension Study Period | Pregnancy | 1 | 2 |
| Extension Study Period | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Copaxone® 40 mg/mL TIW | Total | Copaxone® 20 mg/mL QD |
|---|---|---|---|
| Age, Continuous | 41.0 years STANDARD_DEVIATION 11.15 | 40.5 years STANDARD_DEVIATION 10.91 | 40.1 years STANDARD_DEVIATION 10.67 |
| Body Mass Index | 24.93 kg/m^2 STANDARD_DEVIATION 4.879 | 24.78 kg/m^2 STANDARD_DEVIATION 5.079 | 24.62 kg/m^2 STANDARD_DEVIATION 5.272 |
| Height | 169.4 cm STANDARD_DEVIATION 8.56 | 169.0 cm STANDARD_DEVIATION 8.91 | 168.6 cm STANDARD_DEVIATION 9.24 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized Missing | 6 Participants | 9 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 63 Participants | 122 Participants | 59 Participants |
| Race/Ethnicity, Customized White | 359 Participants | 722 Participants | 363 Participants |
| Sex: Female, Male Female | 288 Participants | 595 Participants | 307 Participants |
| Sex: Female, Male Male | 143 Participants | 266 Participants | 123 Participants |
| Weight | 71.85 kg STANDARD_DEVIATION 16.265 | 71.17 kg STANDARD_DEVIATION 16.373 | 70.49 kg STANDARD_DEVIATION 16.471 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 427 | 1 / 430 | 0 / 392 | 0 / 396 |
| other Total, other adverse events | 121 / 427 | 117 / 430 | 22 / 392 | 15 / 396 |
| serious Total, serious adverse events | 8 / 427 | 13 / 430 | 3 / 392 | 2 / 396 |
Outcome results
Primary
Change From Baseline in the Medication Satisfaction Questionnaire (MSQ) to Month 6 Using a Repeated Measures ANCOVA
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Copaxone® 20 mg/mL QD | Change From Baseline in the Medication Satisfaction Questionnaire (MSQ) to Month 6 Using a Repeated Measures ANCOVA | 5.396 units on a scale | Standard Error 0.0889 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Medication Satisfaction Questionnaire (MSQ) to Month 6 Using a Repeated Measures ANCOVA | 5.717 units on a scale | Standard Error 0.0879 |
Comparison: 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.p-value: <0.00195% CI: [0.1615, 0.4814]Repeated Measures ANCOVA
Secondary
Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA
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
Population: Full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Copaxone® 20 mg/mL QD | Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA | -1.525 units on a scale | Standard Error 0.256 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Beck Depression Inventory II (BDI-II) Total Score to Month 6 Using a Repeated Measures ANCOVA | -1.585 units on a scale | Standard Error 0.2495 |
Comparison: 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.p-value: 0.85195% CI: [-0.6777, 0.5592]Repeated Measures ANCOVA
Secondary
Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA
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
Population: Full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Copaxone® 20 mg/mL QD | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MHI Total Score | 3.136 units on a scale | Standard Error 0.5381 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Behavioral Control subscale | 0.659 units on a scale | Standard Error 0.6133 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Depression subscale | 3.773 units on a scale | Standard Error 0.6433 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MHI Positive Affect subscale | 3.024 units on a scale | Standard Error 0.7306 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Anxiety subscale | 5.468 units on a scale | Standard Error 0.6861 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MHI Positive Affect subscale | 2.932 units on a scale | Standard Error 0.7126 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MHI Total Score | 3.842 units on a scale | Standard Error 0.5249 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Depression subscale | 4.253 units on a scale | Standard Error 0.627 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Behavioral Control subscale | 2.526 units on a scale | Standard Error 0.6 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Mental Health Index (MHI) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | Anxiety subscale | 5.609 units on a scale | Standard Error 0.6695 |
Comparison: 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.p-value: 0.28795% CI: [-0.5947, 1.0074]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.86895% CI: [-1.5179, 1.7991]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.54495% CI: [-1.0734, 2.0348]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.01495% CI: [0.3843, 3.3487]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.91995% CI: [-1.8565, 1.6728]Repeated Measures ANCOVA
Secondary
Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA
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
Population: Full analysis set (FAS). The participant was considered invalid if any of the items were missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Copaxone® 20 mg/mL QD | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Total Score | -2.811 units on a scale | Standard Error 0.5166 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Physical Subscale | -1.483 units on a scale | Standard Error 0.2599 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Cognitive Subscale | -0.965 units on a scale | Standard Error 0.2553 |
| Copaxone® 20 mg/mL QD | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Psychosocial Subscale | -0.306 units on a scale | Standard Error 0.0704 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Psychosocial Subscale | -0.204 units on a scale | Standard Error 0.0685 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Total Score | -3.613 units on a scale | Standard Error 0.5052 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Cognitive Subscale | -1.604 units on a scale | Standard Error 0.2503 |
| Copaxone® 40 mg/mL TIW | Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Total Score and Subscales to Month 6 Using a Repeated Measures ANCOVA | MFIS Physical Subscale | -1.714 units on a scale | Standard Error 0.2535 |
Comparison: 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.p-value: 0.20895% CI: [-2.05, 0.4461]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.4795% CI: [-0.8588, 0.3962]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.04395% CI: [-1.2564, -0.0214]Repeated Measures ANCOVA
Comparison: 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.p-value: 0.23795% CI: [-0.0672, 0.2711]Repeated Measures ANCOVA
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
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Copaxone® 20 mg/mL QD | 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 | 69.740 units on a scale | Standard Error 1.1999 |
| Copaxone® 40 mg/mL TIW | 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 | 79.189 units on a scale | Standard Error 1.2347 |
Comparison: 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.p-value: <0.00195% CI: [6.9538, 11.9429]Repeated Measures ANCOVA
Secondary
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods
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
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE | 219 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 injection-related TEAE | 149 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 Severe TEAE | 4 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >= 1 serious TEAE | 8 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE leading to withdrawal | 18 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious fatal TEAE | 0 Participants |
| Copaxone® 20 mg/mL QD | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious and related TEAE | 1 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 injection-related TEAE | 146 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious and related TEAE | 2 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious fatal TEAE | 0 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 Severe TEAE | 3 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE leading to withdrawal | 13 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >= 1 serious TEAE | 13 Participants |
| Copaxone® 40 mg/mL TIW | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE | 231 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious and related TEAE | 0 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE | 132 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >= 1 serious TEAE | 3 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious fatal TEAE | 0 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 Severe TEAE | 1 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 injection-related TEAE | 38 Participants |
| Copaxone® 40 mg/mL TIW (Switch-Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE leading to withdrawal | 2 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious fatal TEAE | 0 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE leading to withdrawal | 3 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 injection-related TEAE | 25 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >= 1 serious TEAE | 2 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 TEAE | 129 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 Severe TEAE | 0 Participants |
| Copaxone® 40 mg/mL TIW (Extension) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods | >=1 serious and related TEAE | 0 Participants |