Trial Outcomes & Findings for Study to Assess Medication Satisfaction in Patients With Relapsing Remitting Multiple Sclerosis Treated With Copaxone® (NCT NCT02499900)

NCT ID: NCT02499900

Last Updated: 2021-12-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 861 participants
• Primary outcome timeframe: Baseline (Month 0), Months 1, 3 and 6
• Results posted on: 2021-12-09

Participant Flow

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.

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.

Participant milestones

Measure	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.	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.
Core Study Period STARTED	430	431
Core Study Period Safety Analysis Set	427	430
Core Study Period COMPLETED	395	399
Core Study Period NOT COMPLETED	35	32
Completed Core, Continued Into Extension STARTED	395	399
Completed Core, Continued Into Extension COMPLETED	392	397
Completed Core, Continued Into Extension NOT COMPLETED	3	2
Extension Study Period STARTED	392	397
Extension Study Period Safety Analysis Set	392	396
Extension Study Period COMPLETED	380	377
Extension Study Period NOT COMPLETED	12	20

Reasons for withdrawal

Measure	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.	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.
Core Study Period Other	1	4
Core Study Period Lost to Follow-up	1	2
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
Core Study Period Adverse Event	18	14
Core Study Period Death	0	1
Completed Core, Continued Into Extension Physician Decision	1	0
Completed Core, Continued Into Extension Withdrawal by Subject	0	2
Completed Core, Continued Into Extension Did not wish to take injectables drugs	1	0
Completed Core, Continued Into Extension Personal motivation	1	0
Extension Study Period Adverse Event	2	4
Extension Study Period Withdrawal by Subject	5	2
Extension Study Period Physician Decision	2	5
Extension Study Period Pregnancy	1	2
Extension Study Period Lost to Follow-up	2	5
Extension Study Period Other	0	2

Baseline Characteristics

Some participants were missing a baseline weight

Baseline characteristics by cohort

Measure	Copaxone® 20 mg/mL QD n=430 Participants 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.	Copaxone® 40 mg/mL TIW n=431 Participants 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 n=861 Participants Total of all reporting groups
Age, Continuous	40.1 years STANDARD_DEVIATION 10.67 • n=430 Participants	41.0 years STANDARD_DEVIATION 11.15 • n=431 Participants	40.5 years STANDARD_DEVIATION 10.91 • n=861 Participants
Sex: Female, Male Female	307 Participants n=430 Participants	288 Participants n=431 Participants	595 Participants n=861 Participants
Sex: Female, Male Male	123 Participants n=430 Participants	143 Participants n=431 Participants	266 Participants n=861 Participants
Race/Ethnicity, Customized White	363 Participants n=430 Participants	359 Participants n=431 Participants	722 Participants n=861 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=430 Participants	3 Participants n=431 Participants	7 Participants n=861 Participants
Race/Ethnicity, Customized Asian	0 Participants n=430 Participants	0 Participants n=431 Participants	0 Participants n=861 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=430 Participants	0 Participants n=431 Participants	1 Participants n=861 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=430 Participants	0 Participants n=431 Participants	0 Participants n=861 Participants
Race/Ethnicity, Customized Other	59 Participants n=430 Participants	63 Participants n=431 Participants	122 Participants n=861 Participants
Race/Ethnicity, Customized Missing	3 Participants n=430 Participants	6 Participants n=431 Participants	9 Participants n=861 Participants
Weight	70.49 kg STANDARD_DEVIATION 16.471 • n=425 Participants • Some participants were missing a baseline weight	71.85 kg STANDARD_DEVIATION 16.265 • n=424 Participants • Some participants were missing a baseline weight	71.17 kg STANDARD_DEVIATION 16.373 • n=849 Participants • Some participants were missing a baseline weight
Body Mass Index	24.62 kg/m^2 STANDARD_DEVIATION 5.272 • n=425 Participants • Due to the missing baseline weight assessments, BMI could not be calculated for those participants.	24.93 kg/m^2 STANDARD_DEVIATION 4.879 • n=424 Participants • Due to the missing baseline weight assessments, BMI could not be calculated for those participants.	24.78 kg/m^2 STANDARD_DEVIATION 5.079 • n=849 Participants • Due to the missing baseline weight assessments, BMI could not be calculated for those participants.
Height	168.6 cm STANDARD_DEVIATION 9.24 • n=425 Participants • Some participants were missing baseline height data.	169.4 cm STANDARD_DEVIATION 8.56 • n=425 Participants • Some participants were missing baseline height data.	169.0 cm STANDARD_DEVIATION 8.91 • n=850 Participants • Some participants were missing baseline height data.

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=221 Participants 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.	Copaxone® 40 mg/mL TIW n=235 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) 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)	Copaxone® 40 mg/mL TIW (Extension) 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)
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	5.717 units on a scale Standard Error 0.0879	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=216 Participants 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.	Copaxone® 40 mg/mL TIW n=223 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) 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)	Copaxone® 40 mg/mL TIW (Extension) 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)
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	79.189 units on a scale Standard Error 1.2347	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=427 Participants 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.	Copaxone® 40 mg/mL TIW n=428 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) 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)	Copaxone® 40 mg/mL TIW (Extension) 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)
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	-3.613 units on a scale Standard Error 0.5052	—	—
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	-1.714 units on a scale Standard Error 0.2535	—	—
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	-1.604 units on a scale Standard Error 0.2503	—	—
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	-0.204 units on a scale Standard Error 0.0685	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0), Months 1, 3 and 6

Population: Full analysis set.

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

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=427 Participants 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.	Copaxone® 40 mg/mL TIW n=428 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) 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)	Copaxone® 40 mg/mL TIW (Extension) 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)
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	2.526 units on a scale Standard Error 0.6000	—	—
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	3.842 units on a scale Standard Error 0.5249	—	—
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	5.609 units on a scale Standard Error 0.6695	—	—
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	4.253 units on a scale Standard Error 0.6270	—	—
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	2.932 units on a scale Standard Error 0.7126	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0), Months 1, 3 and 6

Population: Full analysis set.

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.

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=422 Participants 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.	Copaxone® 40 mg/mL TIW n=426 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) 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)	Copaxone® 40 mg/mL TIW (Extension) 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)
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 0.2560	-1.585 units on a scale Standard Error 0.2495	—	—

SECONDARY outcome

Timeframe: Core: Day 1 to Month 6 Extension: Month 7 to Month 12

Population: Safety population

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.

Outcome measures

Measure	Copaxone® 20 mg/mL QD n=427 Participants 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.	Copaxone® 40 mg/mL TIW n=430 Participants 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.	Copaxone® 40 mg/mL TIW (Switch-Extension) n=392 Participants 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)	Copaxone® 40 mg/mL TIW (Extension) n=396 Participants 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)
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >= 1 serious TEAE	8 Participants	13 Participants	3 Participants	2 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 TEAE leading to withdrawal	18 Participants	13 Participants	2 Participants	3 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 TEAE	219 Participants	231 Participants	132 Participants	129 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 serious fatal TEAE	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 serious and related TEAE	1 Participants	2 Participants	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 Severe TEAE	4 Participants	3 Participants	1 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) During Both the Core Period and Extension Periods >=1 injection-related TEAE	149 Participants	146 Participants	38 Participants	25 Participants

Adverse Events

Copaxone® 20 mg/mL QD (Core)

Serious events: 8 serious events

Other events: 121 other events

Deaths: 0 deaths

Copaxone® 40 mg/mL TIW (Core)

Serious events: 13 serious events

Other events: 117 other events

Deaths: 1 deaths

Copaxone® 40 mg/mL TIW (Switch-Extension)

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Copaxone® 40 mg/mL TIW (Extension)

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Copaxone® 20 mg/mL QD (Core) n=427 participants at risk Subcutaneous injections of Copaxone 20 mg/mL daily (QD) for the core period from Day 1 to Month 6.	Copaxone® 40 mg/mL TIW (Core) n=430 participants at risk Subcutaneous injections of Copaxone 40 mg/mL three times a week (TIW) for the core period from Day 1 to Month 6.	Copaxone® 40 mg/mL TIW (Switch-Extension) n=392 participants at risk 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)	Copaxone® 40 mg/mL TIW (Extension) n=396 participants at risk 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)
Blood and lymphatic system disorders Leukocytosis	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Cardiac disorders Atrial fibrillation	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Cardiac disorders Cardiomyopathy	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Cardiac disorders Coronary artery disease	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.26% 1/392 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Endocrine disorders Pituitary hyperplasia	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Infections and infestations Erysipelas	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Infections and infestations Escherichia sepsis	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Infections and infestations Pneumonia	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Infections and infestations Pyelonephritis	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.25% 1/396 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Infections and infestations Urinary tract infection	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.26% 1/392 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Fall	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Joint dislocation	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Rib fracture	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.25% 1/396 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Nervous system disorders Multiple sclerosis	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Nervous system disorders Multiple sclerosis relapse	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.26% 1/392 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Nervous system disorders Sciatica	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Psychiatric disorders Depression	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Psychiatric disorders Suicide attempt	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Renal and urinary disorders Acute kidney injury	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.47% 2/430 • Number of events 2 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Renal and urinary disorders Nephrolithiasis	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.26% 1/392 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Renal and urinary disorders Urinary tract obstruction	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Reproductive system and breast disorders Dysfunctional uterine bleeding	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Reproductive system and breast disorders Uterine polyp	0.23% 1/427 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/430 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/427 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.23% 1/430 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/392 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.00% 0/396 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12

Other adverse events

Measure	Copaxone® 20 mg/mL QD (Core) n=427 participants at risk Subcutaneous injections of Copaxone 20 mg/mL daily (QD) for the core period from Day 1 to Month 6.	Copaxone® 40 mg/mL TIW (Core) n=430 participants at risk Subcutaneous injections of Copaxone 40 mg/mL three times a week (TIW) for the core period from Day 1 to Month 6.	Copaxone® 40 mg/mL TIW (Switch-Extension) n=392 participants at risk 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)	Copaxone® 40 mg/mL TIW (Extension) n=396 participants at risk 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)
General disorders Injection site bruising	5.6% 24/427 • Number of events 24 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	4.0% 17/430 • Number of events 17 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.3% 5/392 • Number of events 5 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.0% 4/396 • Number of events 4 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
General disorders Injection site erythema	16.6% 71/427 • Number of events 75 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	14.2% 61/430 • Number of events 65 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	2.6% 10/392 • Number of events 10 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.0% 4/396 • Number of events 4 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
General disorders Injection site haemorrhage	4.7% 20/427 • Number of events 23 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	5.1% 22/430 • Number of events 26 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.51% 2/392 • Number of events 2 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.76% 3/396 • Number of events 3 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
General disorders Injection site pain	19.7% 84/427 • Number of events 92 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	20.7% 89/430 • Number of events 109 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	2.6% 10/392 • Number of events 11 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.3% 5/396 • Number of events 6 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
General disorders Injection site pruritus	13.6% 58/427 • Number of events 61 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	8.6% 37/430 • Number of events 40 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.3% 5/392 • Number of events 5 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	1.0% 4/396 • Number of events 4 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12
General disorders Injection site swelling	8.0% 34/427 • Number of events 34 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	7.4% 32/430 • Number of events 32 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.26% 1/392 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12	0.25% 1/396 • Number of events 1 • - Core study period: Day 1 to Month 6 - Extension study period: Month 7 to Month 12

Additional Information

Director, Clinical Research

Teva Pharmaceutical Industries Ltd.

Phone: +01 215-591-3000

Email: USMedInfo@tevapharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER