Trial Outcomes & Findings for A Study in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate (GA) Injection 40 mg Administered Three Times a Week Compared to Placebo (NCT NCT01067521)

Last Updated: 2021-12-09

Results Overview

Relapses were monitored throughout the study. During the PC Period, two neurologists/physicians assessed subjects' general medical and neurological evaluations separately. A relapse was defined as the appearance of 1+ new neurological abnormalities or the reappearance of 1+ previously observed neurological abnormalities lasting \>= 48 hours and immediately preceded by an improving neurological state of at \>=30 days from onset of previous relapse. An event was counted as a relapse only when the subject's symptoms were accompanied by observed objective neurological changes, consistent with \>= one of the following: - An increase of \>= 0.5 in the Expanded Disability Status Scale (EDSS) score as compared to previous evaluation. - An increase of one grade in the actual score of \>=2 of the 7 functional systems (FS), as compared to previous evaluation. - An increase of 2 grades in the actual score of one FS as compared to the previous evaluation. Adjusted mean values are displayed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1404 participants

Primary outcome timeframe

Day 1 to 12 months

Results posted on

2021-12-09

Participant Flow

A total of 1524 subjects were screened in this study, and 120 (7.9%) subjects failed screening. Of these, 69 did not meet inclusion or exclusion criteria, 30 withdrew from the study and 21 failed screening for other reasons.

1404 subjects were enrolled and randomized in the placebo-controlled (PC) double-blind period. Participants were randomized 2:1 to the treatment arms.

Participant milestones

Participant milestones
Measure	Early Start: GA 40 mg / GA 40 mg Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.
Double-Blind Placebo-Controlled Period STARTED	943	461
Double-Blind Placebo-Controlled Period COMPLETED	859	430
Double-Blind Placebo-Controlled Period NOT COMPLETED	84	31
Open-Label Period STARTED	834	419
Open-Label Period COMPLETED	580	261
Open-Label Period NOT COMPLETED	254	158

Reasons for withdrawal

Reasons for withdrawal
Measure	Early Start: GA 40 mg / GA 40 mg Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.
Double-Blind Placebo-Controlled Period Death	0	1
Double-Blind Placebo-Controlled Period Adverse Event	29	6
Double-Blind Placebo-Controlled Period Withdrawal by Subject	34	17
Double-Blind Placebo-Controlled Period Physician Decision	1	1
Double-Blind Placebo-Controlled Period Refused to sign informed consent	4	1
Double-Blind Placebo-Controlled Period Noncompliance with study drug	2	0
Double-Blind Placebo-Controlled Period Protocol Violation	2	0
Double-Blind Placebo-Controlled Period Pregnancy	7	4
Double-Blind Placebo-Controlled Period Lost to Follow-up	5	1
Open-Label Period Death	3	1
Open-Label Period Adverse Event	30	28
Open-Label Period Withdrawal by Subject	160	88
Open-Label Period Physician Decision	13	11
Open-Label Period Non-compliance with study drug	5	0
Open-Label Period Protocol Violation	3	0
Open-Label Period Pregnancy	14	8
Open-Label Period Teva requested subject to be withdrawn	5	2
Open-Label Period Lost to Follow-up	21	20

Baseline Characteristics

One participant in the Placebo arm was missing the BMI baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Early Start: GA 40 mg / GA 40 mg n=943 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=461 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Total n=1404 Participants Total of all reporting groups
Age, Continuous	37.36 years STANDARD_DEVIATION 9.401 • n=943 Participants	38.12 years STANDARD_DEVIATION 9.222 • n=461 Participants	37.61 years STANDARD_DEVIATION 9.346 • n=1404 Participants
Sex: Female, Male Female	641 Participants n=943 Participants	313 Participants n=461 Participants	954 Participants n=1404 Participants
Sex: Female, Male Male	302 Participants n=943 Participants	148 Participants n=461 Participants	450 Participants n=1404 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=943 Participants	0 Participants n=461 Participants	1 Participants n=1404 Participants
Race/Ethnicity, Customized Asian	2 Participants n=943 Participants	0 Participants n=461 Participants	2 Participants n=1404 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=943 Participants	3 Participants n=461 Participants	15 Participants n=1404 Participants
Race/Ethnicity, Customized Other, not specified	12 Participants n=943 Participants	3 Participants n=461 Participants	15 Participants n=1404 Participants
Race/Ethnicity, Customized White	916 Participants n=943 Participants	455 Participants n=461 Participants	1371 Participants n=1404 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	934 Participants n=943 Participants	460 Participants n=461 Participants	1394 Participants n=1404 Participants
Race/Ethnicity, Customized Hispanic or Latino	9 Participants n=943 Participants	1 Participants n=461 Participants	10 Participants n=1404 Participants
Body Mass Index (BMI)	24.38 kg/m^2 STANDARD_DEVIATION 4.709 • n=942 Participants • One participant in the Placebo arm was missing the BMI baseline measure.	24.44 kg/m^2 STANDARD_DEVIATION 4.804 • n=461 Participants • One participant in the Placebo arm was missing the BMI baseline measure.	24.40 kg/m^2 STANDARD_DEVIATION 4.739 • n=1403 Participants • One participant in the Placebo arm was missing the BMI baseline measure.
Time from First Symptom	7.68 years STANDARD_DEVIATION 6.748 • n=943 Participants	7.61 years STANDARD_DEVIATION 6.360 • n=461 Participants	7.66 years STANDARD_DEVIATION 6.621 • n=1404 Participants
Time from Multiple Sclerosis (MS) Diagnosis	3.70 years STANDARD_DEVIATION 4.982 • n=943 Participants	3.88 years STANDARD_DEVIATION 4.744 • n=461 Participants	3.76 years STANDARD_DEVIATION 4.904 • n=1404 Participants
Number of T1 Gadolinium (Gd)-Enhanced Lesions per Participant at Baseline	1.7 lesions STANDARD_DEVIATION 4.70 • n=943 Participants	1.4 lesions STANDARD_DEVIATION 3.69 • n=461 Participants	1.6 lesions STANDARD_DEVIATION 4.39 • n=1404 Participants
Number of T2 Lesions Per Participant at Baseline	38.0 lesions STANDARD_DEVIATION 26.34 • n=943 Participants	36.7 lesions STANDARD_DEVIATION 26.68 • n=461 Participants	37.5 lesions STANDARD_DEVIATION 26.45 • n=1404 Participants
Sienax Normalized Brain Volume at Baseline	1533.888 mL STANDARD_DEVIATION 110.6107 • n=942 Participants • One participant in the GA40 mg ("Early Start') arm was missing the Sienax normalized brain volume baseline measure.	1537.899 mL STANDARD_DEVIATION 110.7549 • n=461 Participants • One participant in the GA40 mg ("Early Start') arm was missing the Sienax normalized brain volume baseline measure.	1535.206 mL STANDARD_DEVIATION 110.6347 • n=1403 Participants • One participant in the GA40 mg ("Early Start') arm was missing the Sienax normalized brain volume baseline measure.

PRIMARY outcome

Timeframe: Day 1 to 12 months

Population: Intent To Treat (ITT) Analysis Population

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=943 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=461 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
Total Number of Confirmed Relapses During the Placebo Controlled (PC) Treatment Period Estimated by Negative Binomial Regression	0.331 confirmed relapses Standard Error 0.028	0.505 confirmed relapses Standard Error 0.049	—

PRIMARY outcome

Timeframe: Day 1 up to 6.5 years

Population: ITT

The annualized relapse rate (ARR) was calculated for the study by dividing the cumulative number of confirmed relapses by the number of person-years of exposure to treatment. The analysis of the annualized relapse rate is based on estimating a contrast (early start vs delayed start) derived from a baseline-adjusted, Negative Binomial Regression model to the number of confirmed relapses observed during study (post randomization) with an "offset" based on the log of exposure to treatment.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=943 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=461 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
Annualized Rate of Confirmed Relapses Comparing Early Starters to Delayed Starters Estimated by Negative Binomial Regression	0.2621 relapses per year Standard Error 0.0189	0.3146 relapses per year Standard Error 0.0279	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 6, Month 12

Population: ITT. When a subject had both Month 6 and Month 12 scans missing, the subject was excluded from the analysis. When the Month 12 scan was missing, data from Month 6 was used and an offset of log (0.5) introduced. When the Month 6 scan was missing, data from Month 12 was used with an offset of 0.

T2 lesions are hyperintense brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. The cumulative number of T2 lesions at Months 6 and 12 that are new or enlarged as compared to the baseline MRI are offered. Note that the two timeframes (Months 6 and 12) are combined. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions and country or geographical region as covariates.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=884 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=441 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
The Cumulative Number of New/Enlarging T2 Lesions Taken at Month 6 and Month 12 During the Placebo Controlled (PC) Treatment Period Estimated by Negative Binomial Regression	3.650 lesions Standard Error 0.259	5.592 lesions Standard Error 0.490	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 6, Month 12

Population: ITT. When a subject had both Month 6 and Month 12 scans missing, the subject was excluded from the analysis.

The cumulative number of gadolinium (Gd)-enhanced lesions on T1-weighted images at Months 6 and 12 as compared to the baseline MRI are offered. Note that the two timeframes (Months 6 and 12) are combined. Adjusted mean is based on negative binomial regression with an "offset" employing the log of the proportion of the number of the available post-baseline scans to adjust for missing MRI scans (if any), adjusted for baseline number of enhancing lesions on T1-weighted images and country or geographical region as covariates.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=884 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=441 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Month 6 and Month 12 of the Placebo-Controlled (PC) Treatment Period Estimated by Negative Binomial Regression	0.905 lesions Standard Error 0.087	1.639 lesions Standard Error 0.194	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 12

Population: ITT population of participants who had SIENEX brain volume estimates at both baseline and Month 12.

The analysis of brain atrophy as defined by the percentage change in normalized brain volume from baseline to Month 12 was based on the outcome of a contrast (GA 40 mg TIW vs. placebo) derived from a baseline-adjusted ANCOVA. In addition to the treatment group, the model included the following covariates: - SIENAX normalized brain volume at baseline. - The number of enhancing lesions on T1-weighted images at baseline. - country or geographical region. Sienax estimates total brain tissue volume, from a single image, normalised for skull size.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=840 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=423 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
Brain Atrophy As Defined by the Percent of Change in Normalized Brain Volume From Baseline to Month 12 During the Placebo Controlled (PC) Treatment Period	-0.706 percentage change Standard Error 0.037	-0.645 percentage change Standard Error 0.047	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 6, Month 12, Month 36

Population: ITT population of participants with MRIs at both baseline and the designated timeframes.

All data accumulated from screening, the PC Treatment period up to the end of the Open Label (OL) period are combined and referred to as the Long Term Period. T2 lesions are hyperintense brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. The number of T2 lesions at Months 6, 12 and 36 that are new or enlarged as compared to the baseline MRI are offered. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions and country or geographical region as covariates. An "offset" employing the log of the proportion of the number of the available post-placebo-controlled baseline (PCBL) scans was used to adjust for missing MRI scans.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=883 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=440 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
The Number of New/Enlarging T2 Lesions at Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 6	2.872 lesions Standard Error 0.214	3.902 lesions Standard Error 0.43	—
The Number of New/Enlarging T2 Lesions at Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 12	4.484 lesions Standard Error 0.318	7.086 lesions Standard Error 0.699	—
The Number of New/Enlarging T2 Lesions at Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 36	5.836 lesions Standard Error 0.41	8.759 lesions Standard Error 0.82	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 6, Month 12, Month 36

Population: ITT population of participants with MRIs at both baseline and the designated timeframes, inclusive of the proceeding post-baseline timeframes.

All data accumulated from screening, the PC Treatment period up to the end of the Open Label (OL) period are combined and referred to as the Long Term Period. The cumulative number of gadolinium (Gd)-enhanced lesions on T1-weighted images at Months 6, 12 and 36 as compared to the baseline MRI are offered. Adjusted mean is based on negative binomial regression The model was fit using an autoregressive covariance structure. Covariates used: number of enhancing lesions on T1-weighted images at placebo-controlled baseline and country or geographical region. The cumulative number is derived from all the data points before it. For example, if the participant skipped one time point in between the baseline and 36 months, then it cannot be calculated.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=883 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=440 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 6	0.629 lesions Standard Error 0.072	1.131 lesions Standard Error 9.186	—
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 12	1.054 lesions Standard Error 0.115	2.051 lesions Standard Error 0.282	—
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Months 6, 12 and 36 Estimated by Negative Binomial Regression Month 36	1.501 lesions Standard Error 0.168	2.265 lesions Standard Error 0.278	—

SECONDARY outcome

Timeframe: Baseline (Day -7), Month 6, Month 12, Month 36

Population: ITT population of participants with SIENEX brain scans at both baseline and the designated timeframes.

The analysis of brain atrophy as defined by the percentage change in brain volume from baseline to Months 6, 12 and 36 was performed using mixed model for repeated measures (MMRM) with SIENAX normalized brain volume at baseline, number of Gd-enhancing lesions at baseline, and country or geographical region as fixed effects. Sienax estimates total brain tissue volume, from a single image, normalised for skull size.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=872 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=436 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
Brain Atrophy As Defined by the Percent of Change in Brain Volume From Baseline to Months 6, 12 and 36 Estimated by a Mixed Model for Repeated Measures Month 36	-1.935 percentage change Standard Error 0.063	-1.952 percentage change Standard Error 0.09	—
Brain Atrophy As Defined by the Percent of Change in Brain Volume From Baseline to Months 6, 12 and 36 Estimated by a Mixed Model for Repeated Measures Month 6	-0.429 percentage change Standard Error 0.032	-0.345 percentage change Standard Error 0.04	—
Brain Atrophy As Defined by the Percent of Change in Brain Volume From Baseline to Months 6, 12 and 36 Estimated by a Mixed Model for Repeated Measures Month 12	-0.739 percentage change Standard Error 0.035	-0.653 percentage change Standard Error 0.046	—

SECONDARY outcome

Timeframe: Early Start: Day 1 up to 6.5 years Delayed Start - Placebo: Day 1 up to Month 12 Delayed Start - GA: Month 13 up to 6.5 years

Population: Glatiramer Acetate (GA) - Treated Analysis Set The GA-Treated analysis set includes all subjects randomized into the study and treated with at least 1 dose of GA at any time during the study. Analyses includes data collected for these subjects from the first time GA was administered.

Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Outcome measures

Outcome measures
Measure	Early Start: GA 40 mg / GA 40 mg n=943 Participants Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo / GA 40 mg n=419 Participants Participants were administered placebo subcutaneous injections three times a week for 12 months during the double-blind Placebo-Controlled Period. Participants were then switched to glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week during the Open-Label Period from Month 13 up to Year 6.5 until the study ended.	Delayed Start: Placebo n=461 Participants Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.
Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE	777 Participants	322 Participants	284 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Severity of TEAEs: Mild	698 Participants	283 Participants	247 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Severity of TEAEs: Moderate	441 Participants	168 Participants	101 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Severity of TEAEs: Severe	95 Participants	24 Participants	16 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Treatment-related TEAEs	501 Participants	189 Participants	73 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Serious TEAEs	117 Participants	36 Participants	21 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Deaths	3 Participants	1 Participants	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs leading to treatment discontinuation	63 Participants	28 Participants	6 Participants

Adverse Events

Delayed Start: GA 40 mg

Serious events: 36 serious events

Other events: 238 other events

Deaths: 1 deaths

Delayed Start: Placebo

Serious events: 21 serious events

Other events: 167 other events

Deaths: 1 deaths

Early Start: GA 40 mg / GA 40 mg

Serious events: 117 serious events

Other events: 609 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Delayed Start: GA 40 mg n=419 participants at risk After completing the double-blind Placebo-Controlled Period, participants had the option of continuing in the study on glatiramer acetate (GA) 40 mg/ml by subcutaneous injection three times a week until the study ended. This 'Delayed Start' treatment started at Month 13 and continued until the study ended (up to about 6.5 years).	Delayed Start: Placebo n=461 participants at risk Participants were administered placebo subcutaneous injections three times a week from Day 1 to Month 12 during the double-blind Placebo-Controlled Period.	Early Start: GA 40 mg / GA 40 mg n=943 participants at risk Participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the double-blind Placebo-Controlled Period, and then continued that treatment in the Open-label Period from Month 13 up to Year 6.5 until the study ended
General disorders Injection site erythema	25.5% 107/419 • Number of events 122 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	1.7% 8/461 • Number of events 10 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	25.8% 243/943 • Number of events 391 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
General disorders Injection site pain	13.1% 55/419 • Number of events 61 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	2.2% 10/461 • Number of events 10 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	12.2% 115/943 • Number of events 138 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
General disorders Injection site pruritus	5.5% 23/419 • Number of events 24 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	0.43% 2/461 • Number of events 2 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	7.2% 68/943 • Number of events 95 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
General disorders Injection site swelling	5.5% 23/419 • Number of events 23 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	0.65% 3/461 • Number of events 5 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	5.3% 50/943 • Number of events 95 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Infections and infestations Bronchitis	4.8% 20/419 • Number of events 25 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	1.5% 7/461 • Number of events 9 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	5.3% 50/943 • Number of events 65 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Infections and infestations Influenza	6.0% 25/419 • Number of events 33 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	3.7% 17/461 • Number of events 22 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	7.1% 67/943 • Number of events 103 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Infections and infestations Nasopharyngitis	13.4% 56/419 • Number of events 98 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	8.5% 39/461 • Number of events 47 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	17.7% 167/943 • Number of events 346 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Infections and infestations Upper respiratory tract infection	7.6% 32/419 • Number of events 54 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	5.4% 25/461 • Number of events 30 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	10.4% 98/943 • Number of events 158 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Infections and infestations Urinary tract infection	8.6% 36/419 • Number of events 50 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	4.8% 22/461 • Number of events 24 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	10.9% 103/943 • Number of events 165 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Musculoskeletal and connective tissue disorders Back pain	7.9% 33/419 • Number of events 45 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	4.3% 20/461 • Number of events 26 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	10.4% 98/943 • Number of events 150 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Nervous system disorders Headache	9.3% 39/419 • Number of events 83 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	11.9% 55/461 • Number of events 71 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	14.0% 132/943 • Number of events 316 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.
Nervous system disorders Multiple sclerosis relapse	2.4% 10/419 • Number of events 12 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	1.5% 7/461 • Number of events 9 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.	5.1% 48/943 • Number of events 63 • Delayed Start (GA 40 mg): Month 13 up to 6.5 years Delayed Start (Placebo): Day 1 to Month 12 Early Start: (GA 40 mg/ GA 40 mg) Day 1 up to 6.5 years Death details: Delayed Start (GA 40 mg): caused by subarachnoid hemorrhage and brain edema 1027 days after the first dose of GA. Delayed Start (Placebo): cardiopulmonary failure Early Start: Three deaths due to acute cardiac failure, cardio-respiratory arrest, and cardiac arrest occurring 488, 1283 and 1682 days after first dose of GA respectively.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc

Phone: 001-215-591-3000

Email: [email protected]

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.
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