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Trial record 21 of 119 for:    COP1

Safety and Tolerability of Glatiramer Acetate (GLACIER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01874145
Recruitment Status : Completed
First Posted : June 10, 2013
Results First Posted : January 14, 2016
Last Update Posted : January 14, 2016
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: GA 20 mg/mL
Drug: GA 40 mg/mL
Enrollment 209
Recruitment Details  
Pre-assignment Details A total of 218 patients with a confirmed and documented RRMS diagnosis were screened for enrollment into this study. Of the 9 patients who were screened but not randomized, 3 were excluded for not meeting the inclusion criteria, 3 were excluded for meeting an exclusion criterion, and 3 were not enrolled for “other“ reason.
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Period Title: Core Period
Started 101 108
Full Analysis Set 100 108
Completed 98 101
Not Completed 3 7
Reason Not Completed
Non-compliance             1             0
Protocol Violation             1             1
Physician Decision             1             1
Adverse Event             0             1
Withdrawal by Subject             0             4
Period Title: Extension Period
Started 97 [1] 101 [2]
Full Analysis Set 95 101
Completed 91 97
Not Completed 6 4
Reason Not Completed
Adverse Event             3             2
Withdrawal by Subject             2             1
Lost to Follow-up             1             1
[1]
Switchers
[2]
Non-Switchers
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension) Total
Hide Arm/Group Description

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Total of all reporting groups
Overall Number of Baseline Participants 101 108 209
Hide Baseline Analysis Population Description
Intent to treat analysis set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 108 participants 209 participants
50.4  (9.34) 50.9  (11.01) 50.7  (10.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 108 participants 209 participants
Female
83
  82.2%
89
  82.4%
172
  82.3%
Male
18
  17.8%
19
  17.6%
37
  17.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 101 participants 108 participants 209 participants
Not Hispanic or Latino 99 107 206
Hispanic or Latino 2 0 2
Unknown 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 101 participants 108 participants 209 participants
White 96 100 196
Black 5 5 10
Asian 0 3 3
American Indian or Alaskan Native 0 0 0
Pacific Islander 0 0 0
Other 0 0 0
Tobacco user  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 101 participants 108 participants 209 participants
Current 15 8 23
Former 21 29 50
Never Smoked 65 71 136
Time to First MS Symptom  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 108 participants 209 participants
16.2  (10.95) 15.7  (11.10) 15.9  (11.00)
Time from MS Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 108 participants 209 participants
12.1  (10.04) 10.8  (8.55) 11.5  (9.30)
Number of Relapses in 1 Year Prior to Screening  
Mean (Standard Deviation)
Unit of measure:  Relapses
Number Analyzed 101 participants 108 participants 209 participants
0.2  (0.41) 0.2  (0.47) 0.2  (0.44)
Number of Relapses in 2 Years Prior to Screening  
Mean (Standard Deviation)
Unit of measure:  Relapses
Number Analyzed 101 participants 108 participants 209 participants
0.4  (0.74) 0.4  (0.64) 0.4  (0.69)
Expanded Disability Status Scale (EDSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 101 participants 108 participants 209 participants
2.4  (1.38) 2.5  (1.36) 2.4  (1.37)
[1]
Measure Description:

The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The EDSS quantifies disability in eight Functional Systems (FS):

  • pyramidal
  • cerebellar
  • brainstem
  • sensory
  • bowel and bladder
  • visual
  • cerebral
  • other

The scale is from 0 (normal neurological examination) to 10 (Death due to MS). A grade of 2.5 refers to a mild disability in one functional system or minimal disability in two functional systems.

1.Primary Outcome
Title Adjusted Mean Estimates for Injection-Related Adverse Event Rate Per Year in the Core Period
Hide Description

Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria). Rate was calculated as # IR events/the total exposure to study drug in years.

For cases in which more than 1 IR adverse event started on the same date for the same patient, these were counted as 1 IR adverse event for that patient.

Parameter statistics were generated from a Poisson regression model with natural log of treatment duration (years) as an offset variable, and adjusted for baseline EDSS score, treatment group, age, sex, number of relapses in the 2 years prior to screening, in which a contrast comparing treatment groups were constructed. Adjusted mean estimates were adjusted estimates of event rates within treatment group.

Time Frame Day 1 to Month 4
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 101 108
Mean (Standard Error)
Unit of Measure: events per year
70.403  (11.995) 35.275  (7.248)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension), GA 40 mg/mL TIW (Core and Extension)
Comments Adjusted mean estimates were adjusted estimates of event rates within treatment group. The treatment effect parameter estimate was a risk ratio of the GA 40 mg/mL TIW treatment group divided by the GA 20 mg/mL QD treatment group. The p value tested whether the risk ratio was significantly different from 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments The overall significance level for this study was 5% using 2-tailed test.
Method Poisson regression model
Comments Natural log of treatment duration was an offset variable; adjusted for baseline EDSS, treatment group, age, sex, # relapses 2 years prior to screening
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.501
Confidence Interval (2-Sided) 95%
0.338 to 0.743
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.101
Estimation Comments GA 40 mg/mL TIW treatment group / GA 20 mg/mL QD treatment group.
2.Primary Outcome
Title Injection-Related Adverse Event Rate Per Year in the Extension Period
Hide Description

Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria). Rate was calculated as # IR events/the total exposure to study drug in years.

For cases in which more than 1 IR adverse event started on the same date for the same patient, these were counted as 1 IR adverse event for that patient.

Time Frame Month 5 up to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
ITT extension analysis set of participants who had at least one injection-related AE
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 31 33
Measure Type: Number
Unit of Measure: events per year
23.1 28.0
3.Primary Outcome
Title Injection-Related Adverse Events in the Extension Period
Hide Description Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria).
Time Frame Month 5 up to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
ITT extension analysis set of participants who had at least one injection-related AE
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 31 33
Measure Type: Number
Unit of Measure: events
772 979
4.Secondary Outcome
Title Adjusted Mean Estimates for Injection Site Reaction Event Rate Per Year in the Core Period
Hide Description

This outcome includes injection-related adverse events referring to all local injection site reactions (ISR). Rate was calculated as # ISR events/the total exposure to study drug in years.

For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient.

Parameter statistics were generated from a Poisson regression model with natural log of treatment duration (years) as an offset variable, and adjusted for baseline EDSS score, treatment group, age, sex, number of relapses in the 2 years prior to screening, in which a contrast comparing treatment groups were constructed. Adjusted mean estimates were adjusted estimates of event rates within treatment group.

Time Frame Day 1 to Month 4
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 101 108
Mean (Standard Error)
Unit of Measure: events per year
70.392  (12.007) 35.200  (7.247)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension), GA 40 mg/mL TIW (Core and Extension)
Comments Adjusted mean estimates were adjusted estimates of event rates within treatment group. The treatment effect parameter estimate was a risk ratio of the GA 40 mg/mL TIW treatment group divided by the GA 20 mg/mL QD treatment group. The p value tested whether the risk ratio was significantly different from 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments The overall significance level for this study was 5% using 2-tailed test.
Method Poisson regression model
Comments Natural log of treatment duration was an offset variable; adjusted for baseline EDSS, treatment group, age, sex, # relapses 2 years prior to screening
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.500
Confidence Interval (2-Sided) 95%
0.337 to 0.742
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.101
Estimation Comments GA 40 mg/mL TIW treatment group / GA 20 mg/mL QD treatment group
5.Secondary Outcome
Title Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
Hide Description

The physical wellbeing assessment portion of the MSIS-29 is comprised of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. Negative change from baseline scores indicate improvement in physical wellbeing over time.

The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline MSIS-29 physical score, treatment group, month, treatment by month interaction.

Time Frame Month 0 (baseline), Months 1, 2, 4 (or early termination visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 85 92
Mean (Standard Error)
Unit of Measure: units on a scale
1.536  (0.868) -0.522  (0.832)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension), GA 40 mg/mL TIW (Core and Extension)
Comments

To control for type 1 errors, secondary variables were analyzed only if analysis of the primary variable was statistically significant. Gate-keeping procedures offered further control with this hierarchy:

  1. the rate of ISRs
  2. change from baseline to month 4 (change - M4) in MSIS-20 physical wellbeing
  3. change - M4 in MSIS-20 psychological wellbeing
  4. change - M4 in TSQM-9 convenience
  5. change - M4 in TSQM-9 overall satisfaction
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0897
Comments The overall significance level for this study was 5% using 2-tailed test.
Method ANCOVA
Comments In addition to treatment group, month (categorical), treatment-by-month interaction and score at baseline were used as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.058
Confidence Interval (2-Sided) 95%
-4.438 to 0.322
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.206
Estimation Comments GA 40 mg/mL TIW treatment group vs. GA 20 mg/mL QD treatment group.
6.Secondary Outcome
Title Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
Hide Description

The psychological wellbeing assessment portion of the MSIS-29 is comprised of 9 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 9-45. Negative change from baseline scores indicate improvement in psychological wellbeing over time.

The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline MSIS-29 psychological score, treatment group, month, treatment by month interaction.

Time Frame Month 0 (baseline), Months 1, 2 4 (or early termination visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 85 92
Mean (Standard Error)
Unit of Measure: units on a scale
0.738  (0.533) 0.016  (0.512)
7.Secondary Outcome
Title Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score in the Core Period
Hide Description

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on convenience items 4-6, with each question graded on a scale of 1 (extreme dissatisfaction) to 7 (extreme satisfaction). TSQM-9 participant perception of convenience score was calculated as: ([sum (Item 4 to Item 6) – 3] divided by 18) * 100. The full range was -100 to 100, with positive change from baseline indicating improvement.

The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline TSQM convenience score, treatment group, month, treatment by month interaction.

Time Frame Month 0 (baseline), Months 1, 2 4 (or early termination visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 97 105
Mean (Standard Error)
Unit of Measure: units on a scale
1.745  (1.457) 8.751  (1.399)
8.Secondary Outcome
Title Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score in the Core Period
Hide Description

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on global satisfaction, items 7-9. TSQM-9 participant perception of satisfaction score was calculated as: ([sum(Item 7 to Item 9) – 3] divided by 14) * 100. The full range was -100 to 100, with positive change from baseline indicating improvement satisfaction with medication.

The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline TSQM convenience score, treatment group, month, treatment by month interaction.

Time Frame Month 0 (baseline), Months 1, 2 4 (or early termination visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
Hide Arm/Group Description:

Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 97 105
Mean (Standard Error)
Unit of Measure: units on a scale
1.555  (1.489) 0.703  (1.431)
9.Secondary Outcome
Title Injection Site Reaction Event Rate Per Year in the Extension Period
Hide Description

This outcome includes injection-related adverse events referring to all local injection site reactions (ISR). Rate was calculated as # ISR events/the total exposure to study drug in years.

For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient.

Time Frame Month 5 up to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
ITT extension analysis set of participants who had injection site reaction AEs.
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 31 32
Measure Type: Number
Unit of Measure: events per year
22.9 28.0
10.Secondary Outcome
Title Injection Site Reaction Events in the Extension Period
Hide Description

This outcome includes injection-related adverse events referring to all local injection site reactions (ISR).

For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient.

Time Frame Month 5 up to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
ITT extension analysis set of participants who had injection site reaction AEs.
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 31 32
Measure Type: Number
Unit of Measure: events
768 976
11.Secondary Outcome
Title Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Hide Description

The physical wellbeing assessment portion of the MSIS-29 is comprised of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. Negative change from baseline scores indicate improvement in physical wellbeing.

The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.

Time Frame Month 4 (baseline for extension period), Month 8, endpoint visit
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set Extension Period
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 95 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 8 (n=49, 54) -0.6  (8.09) 0.8  (9.53)
Endpoint visit (n=95, 101) 1.1  (7.53) 0.6  (7.60)
12.Secondary Outcome
Title Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Hide Description

The psychological wellbeing assessment portion of the MSIS-29 is comprised of 9 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 9-45. Negative change from baseline scores indicate improvement in psychological wellbeing.

The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.

Time Frame Month 4 (baseline for extension period), Month 8, endpoint visit
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set Extension Period
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 95 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 8 (n=49, 54) 1.2  (4.34) 0.4  (5.78)
Endpoint visit (n=95, 101) 0.9  (5.26) 0.2  (3.83)
13.Secondary Outcome
Title Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score
Hide Description

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on convenience items 4-6, with each question graded on a scale of 1 (extreme dissatisfaction) to 7 (extreme satisfaction). TSQM-9 participant perception of convenience score was calculated as: ([sum (Item 4 to Item 6) – 3] divided by 18) * 100. The full range was -100 to 100, with positive change from baseline indicating improvement.

The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.

Time Frame Month 4 (baseline for extension period), Month 8, endpoint visit
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set Extension Period
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description:
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 95 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 8 (n=50, 54) 4.0  (18.44) -0.2  (10.41)
Endpoint visit (n=95, 101) 4.3  (17.41) -0.2  (13.10)
14.Secondary Outcome
Title Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score
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The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on global satisfaction, items 7-9. TSQM-9 participant perception of satisfaction score was calculated as: ([sum(Item 7 to Item 9) - 3] divided by 14) * 100. The full range was -100 to 100, with positive change from baseline indicating improvement satisfaction with medication.

The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.

Time Frame Month 4 (baseline for extension period), Month 8, endpoint visit
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Full analysis set Extension Period
Arm/Group Title Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
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Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
Overall Number of Participants Analyzed 95 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 8 (n=50, 54) -0.3  (14.50) -1.2  (13.58)
Endpoint visit (n=95, 101) -0.0  (14.32) -1.2  (11.11)
15.Other Pre-specified Outcome
Title Percentage of Participants With Adverse Events Other Than Injection Related Reactions During the Core Period and the Extension Period
Hide Description An adverse event was defined in the protocol as any untoward medical occurrence in a patient that developed or worsened in severity during the conduct of the clinical study of a pharmaceutical product and did not necessarily have a causal relationship to the study drug. This outcome summarizes the % of participants who had AEs other than injection related reactions. Injection-related (IR) adverse events referring to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria).
Time Frame Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
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Safety analysis set
Arm/Group Title GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension) GA 40 mg/mL TIW (Core and Extension)
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Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.

Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.

Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.

During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.

Overall Number of Participants Analyzed 101 108
Measure Type: Number
Unit of Measure: percentage of participants
Core Period (n=101, 108) 35.6 47.2
Extension Period (n=97, 101) 35.1 39.6
Time Frame Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title GA 20 mg/mL QD (Core) GA 40 mg/mL TIW (Core) Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Hide Arm/Group Description Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period. Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period. Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
All-Cause Mortality
GA 20 mg/mL QD (Core) GA 40 mg/mL TIW (Core) Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
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GA 20 mg/mL QD (Core) GA 40 mg/mL TIW (Core) Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/101 (0.99%)      2/108 (1.85%)      0/97 (0.00%)      2/101 (1.98%)    
Gastrointestinal disorders         
Ileitis  1  0/101 (0.00%)  0 0/108 (0.00%)  0 0/97 (0.00%)  0 1/101 (0.99%)  1
General disorders         
Non-cardiac chest pain  1  1/101 (0.99%)  1 0/108 (0.00%)  0 0/97 (0.00%)  0 0/101 (0.00%)  0
Infections and infestations         
Appendicitis  1  0/101 (0.00%)  0 1/108 (0.93%)  1 0/97 (0.00%)  0 0/101 (0.00%)  0
Respiratory tract infection bacterial  1  0/101 (0.00%)  0 1/108 (0.93%)  1 0/97 (0.00%)  0 0/101 (0.00%)  0
Nervous system disorders         
Multiple sclerosis relapse  1  0/101 (0.00%)  0 0/108 (0.00%)  0 0/97 (0.00%)  0 1/101 (0.99%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GA 20 mg/mL QD (Core) GA 40 mg/mL TIW (Core) Switchers: 40 mg/mL TIW (Extension) Non-Switchers: GA 40 mg/mL TIW (Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/101 (57.43%)      66/108 (61.11%)      33/97 (34.02%)      33/101 (32.67%)    
General disorders         
Injection site bruising  1  18/101 (17.82%)  166 8/108 (7.41%)  8 4/97 (4.12%)  10 3/101 (2.97%)  5
Injection site erythema  1  37/101 (36.63%)  1331 41/108 (37.96%)  692 17/97 (17.53%)  253 21/101 (20.79%)  436
Injection site haemorrhage  1  11/101 (10.89%)  43 8/108 (7.41%)  17 3/97 (3.09%)  5 7/101 (6.93%)  10
Injection site mass  1  27/101 (26.73%)  669 28/108 (25.93%)  381 12/97 (12.37%)  122 16/101 (15.84%)  334
Injection site pain  1  41/101 (40.59%)  1692 42/108 (38.89%)  803 19/97 (19.59%)  626 24/101 (23.76%)  594
Injection site pruritus  1  15/101 (14.85%)  398 14/108 (12.96%)  253 6/97 (6.19%)  85 8/101 (7.92%)  81
Injection site swelling  1  24/101 (23.76%)  594 19/108 (17.59%)  170 11/97 (11.34%)  108 7/101 (6.93%)  89
Injection site urticaria  1  13/101 (12.87%)  377 10/108 (9.26%)  175 4/97 (4.12%)  77 7/101 (6.93%)  163
Injection site warmth  1  6/101 (5.94%)  228 4/108 (3.70%)  24 2/97 (2.06%)  27 3/101 (2.97%)  20
Infections and infestations         
Sinusitis  1  3/101 (2.97%)  3 6/108 (5.56%)  6 0/97 (0.00%)  0 2/101 (1.98%)  2
Nervous system disorders         
Dizziness  1  2/101 (1.98%)  3 6/108 (5.56%)  6 5/97 (5.15%)  5 0/101 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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
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Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
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Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01874145     History of Changes
Other Study ID Numbers: GA-MS-303
First Submitted: June 6, 2013
First Posted: June 10, 2013
Results First Submitted: October 12, 2015
Results First Posted: January 14, 2016
Last Update Posted: January 14, 2016