Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Trial Comparing Treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS) With Two Doses of Glatiramer Acetate (GA).

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: NCT00337779
Recruitment Status : Completed
First Posted : June 16, 2006
Results First Posted : May 14, 2010
Last Update Posted : October 10, 2011
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Relapsing Remitting Multiple Sclerosis
Interventions Drug: Glatiramer Acetate (GA) 40 mg
Drug: glatiramer acetate 20 mg
Enrollment 1155
Recruitment Details 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
Pre-assignment Details All subjects underwent evaluations including vital signs (blood pressure, pulse, and temperature,) adverse events, concomitant medications and neurological evaluation prior to study entry.
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 586 569
Completed 534 490
Not Completed 52 79
Reason Not Completed
Withdrawal by Subject             10             12
Sponsor decision             1             1
Physician Decision             3             6
Protocol Violation             1             1
Lost to Follow-up             6             5
Adverse Event             28             51
Pregnancy             3             2
Death             0             1
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 586 569 1155
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 586 participants 569 participants 1155 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
586
 100.0%
569
 100.0%
1155
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 586 participants 569 participants 1155 participants
36.3  (9.0) 36.3  (9.0) 36.3  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 586 participants 569 participants 1155 participants
Female
421
  71.8%
407
  71.5%
828
  71.7%
Male
165
  28.2%
162
  28.5%
327
  28.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 586 participants 569 participants 1155 participants
Argentina 14 14 28
Belgium 0 1 1
Canada 15 13 28
Czech Republic 33 34 67
Estonia 11 12 23
Finland 9 7 16
France 10 11 21
Germany 50 48 98
Hungary 27 27 54
Israel 14 14 28
Italy 47 43 90
Latvia 14 14 28
Lithuania 14 14 28
Netherlands 7 6 13
Poland 36 35 71
Romania 29 28 57
Russian Federation 87 88 175
Spain 23 22 45
United Kingdom 11 10 21
United States 135 128 263
1.Primary Outcome
Title The Rate of Confirmed Relapses During the Double-blind Phase (12 Months).
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 586 569
Mean (Standard Deviation)
Unit of Measure: Number of relapses per patient
0.28  (0.58) 0.27  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate 20 mg, Glatiramer Acetate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4859
Comments [Not Specified]
Method Regression, Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0732
Confidence Interval (2-Sided) 95%
0.8799 to 1.3090
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1013
Estimation Comments 980 subjects randomized into two arms provide approximately 90% power to detect significant difference between groups of 30% or more in rate of confirmed relapses.
2.Secondary Outcome
Title The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan.
Hide Description The 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 586 569
Mean (Standard Deviation)
Unit of Measure: T2 Lesions
2.87  (6.57) 2.72  (8.36)
3.Secondary Outcome
Title The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below).
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Frequent MRI cohort
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 121 101
Log Mean (Standard Deviation)
Unit of Measure: T1 Enhancing Lesions
2.83  (6.58) 3.49  (8.19)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/586 (4.27%)      24/569 (4.22%)    
Cardiac disorders     
Coronary Artery Disease  0/586 (0.00%)  0 1/569 (0.18%)  1
Myocardial Infarction  0/586 (0.00%)  0 1/569 (0.18%)  1
Palpitations  1/586 (0.17%)  1 0/569 (0.00%)  0
Supraventricular Tachycardia  0/586 (0.00%)  0 1/569 (0.18%)  1
Tachycardia  0/586 (0.00%)  0 1/569 (0.18%)  1
Ear and labyrinth disorders     
Vertigo  2/586 (0.34%)  2 0/569 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain  1/586 (0.17%)  1 1/569 (0.18%)  1
Constipation  0/586 (0.00%)  0 1/569 (0.18%)  1
Diarrhoea  0/586 (0.00%)  0 1/569 (0.18%)  1
Intestinal Obstruction  1/586 (0.17%)  1 0/569 (0.00%)  0
Nausea  0/586 (0.00%)  0 1/569 (0.18%)  1
Swollen Tongue  1/586 (0.17%)  1 0/569 (0.00%)  0
Vomiting  0/586 (0.00%)  0 1/569 (0.18%)  1
General disorders     
Chest Discomfort  1/586 (0.17%)  1 0/569 (0.00%)  0
Chest Pain  0/586 (0.00%)  0 2/569 (0.35%)  2
Chillls  1/586 (0.17%)  1 1/569 (0.18%)  1
Face Oedema  0/586 (0.00%)  0 1/569 (0.18%)  1
Palatal Oedema  1/586 (0.17%)  1 0/569 (0.00%)  0
Swelling Face  0/586 (0.00%)  0 1/569 (0.18%)  1
Pyrexia  1/586 (0.17%)  1 0/569 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis Acute  1/586 (0.17%)  1 0/569 (0.00%)  0
Cholelithiasis  1/586 (0.17%)  1 0/569 (0.00%)  0
Biliary Dyskinesai 1 [1]  0/586 (0.00%)  0 1/569 (0.18%)  1
Immune system disorders     
Anaphylactic Reaction  1/586 (0.17%)  1 0/569 (0.00%)  0
Anaphylactic Shock  0/586 (0.00%)  0 1/569 (0.18%)  1
Hypersensititvity  0/586 (0.00%)  0 2/569 (0.35%)  2
Infections and infestations     
Bronchitis  0/586 (0.00%)  0 2/569 (0.35%)  2
Candidiasis 1 [2]  1/586 (0.17%)  1 0/569 (0.00%)  0
Herpes Zoster  1/586 (0.17%)  1 0/569 (0.00%)  0
Device Related Infection  1/586 (0.17%)  1 0/569 (0.00%)  0
Influenza  0/586 (0.00%)  0 1/569 (0.18%)  1
Pyelonephritis Chronic  1/586 (0.17%)  1 0/569 (0.00%)  0
Injury, poisoning and procedural complications     
Complicated Fracture  1/586 (0.17%)  1 0/569 (0.00%)  0
Crush Injury  0/586 (0.00%)  0 1/569 (0.18%)  1
Multiple Fractures  0/586 (0.00%)  0 1/569 (0.18%)  1
Fall  0/586 (0.00%)  0 1/569 (0.18%)  1
Investigations     
Arteriogram Coronary 1 [3]  0/586 (0.00%)  0 1/569 (0.18%)  1
Troponin Increased 1 [4]  0/586 (0.00%)  0 1/569 (0.18%)  1
Metabolism and nutrition disorders     
Diabetes Mellitus  0/586 (0.00%)  0 1/569 (0.18%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1/586 (0.17%)  1 0/569 (0.00%)  0
Chondropathy 1 [5]  1/586 (0.17%)  1 0/569 (0.00%)  0
Back Pain  0/586 (0.00%)  0 1/569 (0.18%)  1
Muscular Weakness  1/586 (0.17%)  1 0/569 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast Cancer  2/586 (0.34%)  2 1/569 (0.18%)  1
Fibroadenoma of Breast 1 [6]  1/586 (0.17%)  1 0/569 (0.00%)  0
Metastases to Lymph Nodes  1/586 (0.17%)  1 0/569 (0.00%)  0
Nervous system disorders     
Aphasia  0/586 (0.00%)  0 1/569 (0.18%)  1
Presyncope 1 [7]  0/586 (0.00%)  0 1/569 (0.18%)  1
Facial Palsy  0/586 (0.00%)  0 1/569 (0.18%)  1
Tension Headache  1/586 (0.17%)  1 0/569 (0.00%)  0
Migraine  1/586 (0.17%)  1 0/569 (0.00%)  0
Multiple Sclerosis Relapse  0/586 (0.00%)  0 1/569 (0.18%)  1
Radicular Syndrome 1 [8]  0/586 (0.00%)  0 1/569 (0.18%)  1
Paraesthesia  1/586 (0.17%)  1 1/569 (0.18%)  1
Loss of Consciousness 1 [9]  0/586 (0.00%)  0 1/569 (0.18%)  1
Psychiatric disorders     
Panic Attack 1 [10]  1/586 (0.17%)  1 0/569 (0.00%)  0
Anxiety  0/586 (0.00%)  0 1/569 (0.18%)  2
Psychotic Disorder  0/586 (0.00%)  0 1/569 (0.18%)  1
Renal and urinary disorders     
Neophrolithiasis  1/586 (0.17%)  1 0/569 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1/586 (0.17%)  1 4/569 (0.70%)  4
Skin and subcutaneous tissue disorders     
Angioedema  0/586 (0.00%)  0 1/569 (0.18%)  1
Surgical and medical procedures     
Cholecystectomy  1/586 (0.17%)  1 0/569 (0.00%)  0
Coronary Arterial Stent Insertion  0/586 (0.00%)  0 1/569 (0.18%)  1
Laparoscopy  1/586 (0.17%)  1 0/569 (0.00%)  0
Malignant Breast Lump Removal  1/586 (0.17%)  1 0/569 (0.00%)  0
Mastectomy  1/586 (0.17%)  1 0/569 (0.00%)  0
Oophorectomy  1/586 (0.17%)  1 0/569 (0.00%)  0
Spinal Laminectomy  1/586 (0.17%)  1 0/569 (0.00%)  0
Tonsillectomy  1/586 (0.17%)  1 0/569 (0.00%)  0
Varicose Vein Operation  1/586 (0.17%)  1 0/569 (0.00%)  0
Vascular disorders     
Deep Vein Thrombosis  1/586 (0.17%)  1 0/569 (0.00%)  0
Blood Pressure Increased 1 [11]  0/586 (0.00%)  0 1/569 (0.18%)  1
1
Term from vocabulary, MedDRA (11.0)
[1]
Gallbladder Disorder
[2]
Fungal Infection
[3]
Diagnostic Procedure
[4]
Laboratory Abnormal
[5]
Arthropathy
[6]
Breast Neoplasm
[7]
Dizziness
[8]
Neuropathy Peripheral
[9]
Syncope
[10]
Agitation
[11]
Hypertension
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.0%
Glatiramer Acetate 20 mg Glatiramer Acetate 40 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   499/586 (85.15%)      490/569 (86.12%)    
Gastrointestinal disorders     
Nausea  33/586 (5.63%)  41 33/569 (5.80%)  45
General disorders     
Fatigue 1 [1]  39/586 (6.66%)  43 41/569 (7.21%)  44
Chest Discomfort  32/586 (5.46%)  43 28/569 (4.92%)  33
Injection Erythema  183/586 (31.23%)  200 196/569 (34.45%)  231
Injection Site Bruising  31/586 (5.29%)  35 21/569 (3.69%)  22
Injection Site Irritation 1 [2]  57/586 (9.73%)  62 42/569 (7.38%)  47
Injection Site Induration 1 [3]  46/586 (7.85%)  47 54/569 (9.49%)  62
Injection Site Mass  53/586 (9.04%)  55 63/569 (11.07%)  70
Injection Site Swelling 1 [4]  47/586 (8.02%)  49 55/569 (9.67%)  58
Injection Site Pain  109/586 (18.60%)  123 99/569 (17.40%)  112
Injection Site Pruritus  90/586 (15.36%)  95 93/569 (16.34%)  99
Pain in Extremity  30/586 (5.12%)  32 19/569 (3.34%)  23
Infections and infestations     
Upper Respiratory Tract Infection  49/586 (8.36%)  65 54/569 (9.49%)  68
Nasopharyngitis 1 [5]  78/586 (13.31%)  102 74/569 (13.01%)  95
Urinary Tract Infection  43/586 (7.34%)  50 30/569 (5.27%)  38
Musculoskeletal and connective tissue disorders     
Back Pain  28/586 (4.78%)  34 36/569 (6.33%)  39
Nervous system disorders     
Headache  63/586 (10.75%)  115 68/569 (11.95%)  113
Depression  23/586 (3.92%)  24 36/569 (6.33%)  36
Dizziness  30/586 (5.12%)  45 26/569 (4.57%)  29
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  44/586 (7.51%)  67 54/569 (9.49%)  79
Vascular disorders     
Flushing 1 [6]  26/586 (4.44%)  42 36/569 (6.33%)  49
1
Term from vocabulary, MedDRA (11.0)
[1]
Asthenia
[2]
Injection Site Inflamation
[3]
Injection Site Mass
[4]
Injection Site Oedema
[5]
Pharyngitis
[6]
Vasodilatation
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
Name/Title: Chen Duksin, MD
Organization: Teva Pharmaceutical Industries, Ltd.
Phone: 972-9-863-4642
Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT00337779     History of Changes
Other Study ID Numbers: GA/9016 (FORTE)
First Submitted: June 14, 2006
First Posted: June 16, 2006
Results First Submitted: January 18, 2010
Results First Posted: May 14, 2010
Last Update Posted: October 10, 2011