Trial Outcomes & Findings for Clinical Trial Comparing Treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS) With Two Doses of Glatiramer Acetate (GA). (NCT NCT00337779)
NCT ID: NCT00337779
Last Updated: 2011-10-10
Results Overview
A confirmed relapse is defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities. This change in clinical state must last at least 48 hours and be immediately preceded by an improving neurological state of at least thirty (30) days from onset of previous relapse.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1155 participants
Primary outcome timeframe
12 months
Results posted on
2011-10-10
Participant Flow
Study was conducted according to laws, regulations and administrative provisions related to implementation of Good Clinical Practice as applicable by legislation directives and Standard Operating Procedures. Subjects entered study after being informed and given time to contemplate consent. Enrollment began September 2006 and completed May 2007
All subjects underwent evaluations including vital signs (blood pressure, pulse, and temperature,) adverse events, concomitant medications and neurological evaluation prior to study entry.
Participant milestones
| Measure |
Glatiramer Acetate 20 mg
|
Glatiramer Acetate 40 mg
|
|---|---|---|
|
Overall Study
STARTED
|
586
|
569
|
|
Overall Study
COMPLETED
|
534
|
490
|
|
Overall Study
NOT COMPLETED
|
52
|
79
|
Reasons for withdrawal
| Measure |
Glatiramer Acetate 20 mg
|
Glatiramer Acetate 40 mg
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
10
|
12
|
|
Overall Study
Sponsor decision
|
1
|
1
|
|
Overall Study
Physician Decision
|
3
|
6
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
6
|
5
|
|
Overall Study
Adverse Event
|
28
|
51
|
|
Overall Study
Pregnancy
|
3
|
2
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Clinical Trial Comparing Treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS) With Two Doses of Glatiramer Acetate (GA).
Baseline characteristics by cohort
| Measure |
Glatiramer Acetate 20 mg
n=586 Participants
|
Glatiramer Acetate 40 mg
n=569 Participants
|
Total
n=1155 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
586 Participants
n=5 Participants
|
569 Participants
n=7 Participants
|
1155 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
36.3 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
36.3 years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
36.3 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
421 Participants
n=5 Participants
|
407 Participants
n=7 Participants
|
828 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
165 Participants
n=5 Participants
|
162 Participants
n=7 Participants
|
327 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
15 participants
n=5 Participants
|
13 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
33 participants
n=5 Participants
|
34 participants
n=7 Participants
|
67 participants
n=5 Participants
|
|
Region of Enrollment
Estonia
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
France
|
10 participants
n=5 Participants
|
11 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
50 participants
n=5 Participants
|
48 participants
n=7 Participants
|
98 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
27 participants
n=5 Participants
|
27 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
47 participants
n=5 Participants
|
43 participants
n=7 Participants
|
90 participants
n=5 Participants
|
|
Region of Enrollment
Latvia
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Lithuania
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
36 participants
n=5 Participants
|
35 participants
n=7 Participants
|
71 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
29 participants
n=5 Participants
|
28 participants
n=7 Participants
|
57 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
87 participants
n=5 Participants
|
88 participants
n=7 Participants
|
175 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
23 participants
n=5 Participants
|
22 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
135 participants
n=5 Participants
|
128 participants
n=7 Participants
|
263 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: ITT
A confirmed relapse is defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities. This change in clinical state must last at least 48 hours and be immediately preceded by an improving neurological state of at least thirty (30) days from onset of previous relapse.
Outcome measures
| Measure |
Glatiramer Acetate 20 mg
n=586 Participants
|
Glatiramer Acetate 40 mg
n=569 Participants
|
|---|---|---|
|
The Rate of Confirmed Relapses During the Double-blind Phase (12 Months).
|
0.28 Number of relapses per patient
Standard Deviation 0.58
|
0.27 Number of relapses per patient
Standard Deviation 0.54
|
SECONDARY outcome
Timeframe: 12 monthsThe analysis of this endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression including the number of T1 Gd-enhancing lesions at baseline, the volume of T2 lesions at baseline and (pooled) center as covariates.
Outcome measures
| Measure |
Glatiramer Acetate 20 mg
n=586 Participants
|
Glatiramer Acetate 40 mg
n=569 Participants
|
|---|---|---|
|
The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan.
|
2.87 T2 Lesions
Standard Deviation 6.57
|
2.72 T2 Lesions
Standard Deviation 8.36
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Frequent MRI cohort
The Frequent MRI Cohort was a subset of subjects consisting of 234 subjects, for whom MRI scans were performed at months 0 (baseline), 1, 2, 3, 6, 9 and 12. Analysis of the endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression with an "offset" variable employing the log of the porportion of the number of available post-baseline scans to adjust for missing MRI scans (if any) and including the number of T1 Gd-enhancing lesions at baseline and (pooled) center as covariates.
Outcome measures
| Measure |
Glatiramer Acetate 20 mg
n=121 Participants
|
Glatiramer Acetate 40 mg
n=101 Participants
|
|---|---|---|
|
The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below).
|
2.83 T1 Enhancing Lesions
Standard Deviation 6.58
|
3.49 T1 Enhancing Lesions
Standard Deviation 8.19
|
Adverse Events
Glatiramer Acetate 20 mg
Serious events: 25 serious events
Other events: 499 other events
Deaths: 0 deaths
Glatiramer Acetate 40 mg
Serious events: 24 serious events
Other events: 490 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Glatiramer Acetate 20 mg
n=586 participants at risk
|
Glatiramer Acetate 40 mg
n=569 participants at risk
|
|---|---|---|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo
|
0.34%
2/586 • Number of events 2
|
0.00%
0/569
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.17%
1/586 • Number of events 1
|
0.18%
1/569 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Gastrointestinal disorders
Swollen Tongue
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
General disorders
Chest Discomfort
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
General disorders
Chest Pain
|
0.00%
0/586
|
0.35%
2/569 • Number of events 2
|
|
General disorders
Chillls
|
0.17%
1/586 • Number of events 1
|
0.18%
1/569 • Number of events 1
|
|
General disorders
Face Oedema
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
General disorders
Palatal Oedema
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
General disorders
Swelling Face
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
General disorders
Pyrexia
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Hepatobiliary disorders
Biliary Dyskinesai
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Immune system disorders
Anaphylactic Reaction
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Immune system disorders
Anaphylactic Shock
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Immune system disorders
Hypersensititvity
|
0.00%
0/586
|
0.35%
2/569 • Number of events 2
|
|
Infections and infestations
Bronchitis
|
0.00%
0/586
|
0.35%
2/569 • Number of events 2
|
|
Infections and infestations
Candidiasis
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Infections and infestations
Herpes Zoster
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Infections and infestations
Device Related Infection
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Infections and infestations
Influenza
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Infections and infestations
Pyelonephritis Chronic
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Injury, poisoning and procedural complications
Complicated Fracture
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Injury, poisoning and procedural complications
Crush Injury
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Injury, poisoning and procedural complications
Multiple Fractures
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Investigations
Arteriogram Coronary
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Investigations
Troponin Increased
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Musculoskeletal and connective tissue disorders
Chondropathy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.34%
2/586 • Number of events 2
|
0.18%
1/569 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of Breast
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Lymph Nodes
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Nervous system disorders
Aphasia
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Presyncope
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Facial Palsy
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Tension Headache
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Nervous system disorders
Migraine
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Nervous system disorders
Multiple Sclerosis Relapse
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Radicular Syndrome
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
0.17%
1/586 • Number of events 1
|
0.18%
1/569 • Number of events 1
|
|
Nervous system disorders
Loss of Consciousness
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Psychiatric disorders
Panic Attack
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/586
|
0.18%
1/569 • Number of events 2
|
|
Psychiatric disorders
Psychotic Disorder
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Renal and urinary disorders
Neophrolithiasis
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.17%
1/586 • Number of events 1
|
0.70%
4/569 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Surgical and medical procedures
Cholecystectomy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Coronary Arterial Stent Insertion
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Surgical and medical procedures
Laparoscopy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Malignant Breast Lump Removal
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Mastectomy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Oophorectomy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Spinal Laminectomy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Tonsillectomy
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Surgical and medical procedures
Varicose Vein Operation
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.17%
1/586 • Number of events 1
|
0.00%
0/569
|
|
Vascular disorders
Blood Pressure Increased
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/586
|
0.18%
1/569 • Number of events 1
|
Other adverse events
| Measure |
Glatiramer Acetate 20 mg
n=586 participants at risk
|
Glatiramer Acetate 40 mg
n=569 participants at risk
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.6%
33/586 • Number of events 41
|
5.8%
33/569 • Number of events 45
|
|
General disorders
Fatigue
|
6.7%
39/586 • Number of events 43
|
7.2%
41/569 • Number of events 44
|
|
General disorders
Chest Discomfort
|
5.5%
32/586 • Number of events 43
|
4.9%
28/569 • Number of events 33
|
|
General disorders
Injection Erythema
|
31.2%
183/586 • Number of events 200
|
34.4%
196/569 • Number of events 231
|
|
General disorders
Injection Site Bruising
|
5.3%
31/586 • Number of events 35
|
3.7%
21/569 • Number of events 22
|
|
General disorders
Injection Site Irritation
|
9.7%
57/586 • Number of events 62
|
7.4%
42/569 • Number of events 47
|
|
General disorders
Injection Site Induration
|
7.8%
46/586 • Number of events 47
|
9.5%
54/569 • Number of events 62
|
|
General disorders
Injection Site Mass
|
9.0%
53/586 • Number of events 55
|
11.1%
63/569 • Number of events 70
|
|
General disorders
Injection Site Swelling
|
8.0%
47/586 • Number of events 49
|
9.7%
55/569 • Number of events 58
|
|
General disorders
Injection Site Pain
|
18.6%
109/586 • Number of events 123
|
17.4%
99/569 • Number of events 112
|
|
General disorders
Injection Site Pruritus
|
15.4%
90/586 • Number of events 95
|
16.3%
93/569 • Number of events 99
|
|
General disorders
Pain in Extremity
|
5.1%
30/586 • Number of events 32
|
3.3%
19/569 • Number of events 23
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
8.4%
49/586 • Number of events 65
|
9.5%
54/569 • Number of events 68
|
|
Infections and infestations
Nasopharyngitis
|
13.3%
78/586 • Number of events 102
|
13.0%
74/569 • Number of events 95
|
|
Infections and infestations
Urinary Tract Infection
|
7.3%
43/586 • Number of events 50
|
5.3%
30/569 • Number of events 38
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.8%
28/586 • Number of events 34
|
6.3%
36/569 • Number of events 39
|
|
Nervous system disorders
Headache
|
10.8%
63/586 • Number of events 115
|
12.0%
68/569 • Number of events 113
|
|
Nervous system disorders
Depression
|
3.9%
23/586 • Number of events 24
|
6.3%
36/569 • Number of events 36
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.5%
44/586 • Number of events 67
|
9.5%
54/569 • Number of events 79
|
|
Vascular disorders
Flushing
|
4.4%
26/586 • Number of events 42
|
6.3%
36/569 • Number of events 49
|
|
Nervous system disorders
Dizziness
|
5.1%
30/586 • Number of events 45
|
4.6%
26/569 • Number of events 29
|
Additional Information
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