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Safety and Efficacy Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing-Remitting Multiple Sclerosis (SELECT)

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ClinicalTrials.gov Identifier: NCT00390221
Recruitment Status : Completed
First Posted : October 19, 2006
Results First Posted : July 11, 2016
Last Update Posted : July 11, 2016
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Biological: BIIB019 (Daclizumab High Yield Process)
Drug: Placebo
Enrollment 621
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description Placebo administered as 3 subcutaneous (SC) injections every 4 weeks for up to 52 weeks 150 mg Daclizumab High Yield Process (DAC HYP) administered as 3 SC injections every 4 weeks for up to 52 weeks 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Period Title: Overall Study
Started 204 208 209
Completed 186 188 194
Not Completed 18 20 15
Reason Not Completed
Lost to Follow-up             0             3             0
Adverse Event             1             4             3
Investigator Decision             0             0             1
Withdrawal by Subject             13             9             7
Subject Non-compliance             1             0             2
Not Specified             3             4             2
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP Total
Hide Arm/Group Description Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks Total of all reporting groups
Overall Number of Baseline Participants 204 208 209 621
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 204 participants 208 participants 209 participants 621 participants
36.6  (9.02) 35.3  (8.94) 35.2  (8.67) 35.7  (8.88)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 204 participants 208 participants 209 participants 621 participants
18 to 19 years 1 4 5 10
20 to 29 years 46 55 53 154
30 to 39 years 79 73 90 242
40 to 49 years 60 67 49 176
50 to 55 years 18 9 12 39
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 208 participants 209 participants 621 participants
Female
128
  62.7%
140
  67.3%
134
  64.1%
402
  64.7%
Male
76
  37.3%
68
  32.7%
75
  35.9%
219
  35.3%
1.Primary Outcome
Title Adjusted Annualized Relapse Rate Between Baseline and Week 52
Hide Description Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of subject-years followed in the study.
Time Frame Baseline through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: all randomized participants who received at least 1 dose of study medication (excluding 21 participants from a single site due to a protocol violation in dosing).
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description:
Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks
150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Number of Participants Analyzed 196 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per person-years
0.458
(0.370 to 0.566)
0.211
(0.155 to 0.287)
0.230
(0.172 to 0.308)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 150 mg DAC HYP
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments adjusted for the number of relapses in the 1 year prior to study entry, baseline Expanded Disability Status Scale (<=2.5 vs > 2.5), and age (<=35 vs >35)
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.461
Confidence Interval (2-Sided) 95%
0.318 to 0.668
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 300 mg DAC HYP
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments adjusted for the number of relapses in the 1 year prior to study entry, baseline Expanded Disability Status Scale (<=2.5 vs > 2.5), and age (<=35 vs >35)
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.503
Confidence Interval (2-Sided) 95%
0.352 to 0.721
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Number of New Gadolinium (Gd)-Enhancing Lesions Between Week 8 and Week 24
Hide Description Gd-enhancing lesions are detected when Gd leaks into a perivascular space due to local breakdown of the blood-brain barrier, indicating the presence of active inflammation. For participants with missing data the last valid nonbaseline measurement was carried forward if the participant was missing only 1 or 2 consecutive postbaseline scans. Otherwise the mean based on treatment group and visit was used as the imputed value. Estimated from a negative binomial model adjusted for the baseline number of Gd-enhancing lesions.
Time Frame Week 8 through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Magnetic Resonance Imaging (MRI) Intensive Population: a protocol-defined subset of participants consisting of the first 307 participants enrolled in the study with non-missing baseline values.
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description:
Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks
150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Number of Participants Analyzed 104 101 102
Mean (95% Confidence Interval)
Unit of Measure: lesions
4.79
(3.56 to 6.43)
1.46
(1.05 to 2.03)
1.03
(0.73 to 1.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 300 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments adjusted for the baseline number of Gd-enhancing lesions
Method of Estimation Estimation Parameter Percent Reduction
Estimated Value 78.44
Confidence Interval (2-Sided) 95%
65.97 to 86.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 150 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments adjusted for the baseline number of Gd-enhancing lesions
Method of Estimation Estimation Parameter Percent Reduction
Estimated Value 69.47
Confidence Interval (2-Sided) 95%
52.40 to 80.41
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjusted Mean Number of New or Newly-enlarging T2 Hyperintense Lesions at Week 52
Hide Description Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: all randomized subjects who received at least 1 dose of study medication (excluding 21 subjects from a single site due to a protocol violation in dosing) with a non-missing value at baseline.
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description:
Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks
150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Number of Participants Analyzed 195 199 200
Mean (95% Confidence Interval)
Unit of Measure: lesions
8.13
(6.65 to 9.94)
2.42
(1.96 to 2.99)
1.73
(1.39 to 2.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 300 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments adjusted for baseline number of T2 lesions
Method of Estimation Estimation Parameter Percent Reduction
Estimated Value 78.73
Confidence Interval (2-Sided) 95%
71.33 to 84.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 150 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments adjusted for baseline number of T2 lesions
Method of Estimation Estimation Parameter Percent Reduction
Estimated Value 70.23
Confidence Interval (2-Sided) 95%
59.94 to 77.88
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Participants Who Relapsed at Week 52
Hide Description Estimated cumulative proportion of participants relapsed at Week 52, based on the Kaplan-Meier product limit method. Only relapses confirmed by the Independent Neurology Evaluation Committee were included in the analysis.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: all randomized subjects who received at least 1 dose of study medication (excluding 21 subjects from a single site due to a protocol violation in dosing). Participants who did not experience a relapse prior to switching to alternative MS medications or withdrawal from study were censored.
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description:
Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks
150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Number of Participants Analyzed 196 201 203
Measure Type: Number
Unit of Measure: proportion of participants
0.36 0.19 0.20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 300 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments Covariates included were number of relapses in the 1 year prior to study entry (p=0.001), baseline Expanded Disability Status Scale (<=2.5 versus >2.5, p=0.449), and age (<=35 versus >35, p=0.026).
Method Cox Proportional Hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.33 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 150 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Covariates included were number of relapses in the 1 year prior to study entry (p=0.001), baseline Expanded Disability Status Scale (<=2.5 versus >2.5, p=0.449), and age (<=35 versus >35, p=0.026).
Method Cox Proportional Hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.30 to 0.67
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Impact Score at Week 52
Hide Description The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient’s perspective; it measures 20 physical items and 9 psychological items. Responses use a 5 point Likert scale range from 1 to 5. All questions are to be answered. The total score is the sum of points for all 29 questions, with a minimum score of 29, and a maximum score of 145. A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a subject's functioning.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: all randomized subjects who received at least 1 dose of study medication (excluding 21 subjects from a single site due to a protocol violation in dosing).
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP
Hide Arm/Group Description:
Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks
150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Number of Participants Analyzed 196 201 203
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.0  (13.52) -1.0  (11.80) 1.4  (13.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 300 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1284
Comments Analysis of variance for difference between treatment groups, controlling for baseline score.
Method Analysis of Variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Mean Change
Estimated Value -1.93
Confidence Interval (2-Sided) 95%
-4.42 to 0.56
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 150 mg DAC HYP
Comments For each of the secondary endpoints, a sequential closed testing procedure was used, with the first comparison (the DAC HYP 300 mg group versus placebo) and the second comparison (the DAC HYP 150 mg group versus placebo). Secondary endpoints were rank prioritized, in the order presented. If statistical significance was not achieved for an endpoint, all endpoints(s) of a lower rank were not considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Analysis of Variance
Comments Analysis of variance for difference between treatment groups, controlling for baseline score.
Method of Estimation Estimation Parameter Relative Mean Change
Estimated Value -4.27
Confidence Interval (2-Sided) 95%
-6.76 to -1.78
Estimation Comments [Not Specified]
Time Frame AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo 150 mg DAC HYP 300 mg DAC HYP Total Active
Hide Arm/Group Description Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks 150 mg or 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
All-Cause Mortality
Placebo 150 mg DAC HYP 300 mg DAC HYP Total Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 150 mg DAC HYP 300 mg DAC HYP Total Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   53/204 (25.98%)   32/208 (15.38%)   36/209 (17.22%)   68/417 (16.31%) 
Blood and lymphatic system disorders         
Leukocytosis  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Lymphadenopathy  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Cardiac disorders         
Angina unstable  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Atrial fibrillation  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Myocardial ischaemia  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Endocrine disorders         
Autoimmune thyroiditis  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Diabetes insipidus  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Eye disorders         
Retinal vein occlusion  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Gastrointestinal disorders         
Colitis ischaemic  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Crohn's disease  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Gastritis  1  1/204 (0.49%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Gastroduodenitis  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Gastrooesophageal reflux disease  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Hepatobiliary disorders         
Cholecystitis chronic  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Cholelithiasis  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Hepatitis toxic  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Jaundice  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Immune system disorders         
Hypersensitivity  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Infections and infestations         
Appendicitis  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Chronic Hepatitis B  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Cytomegalovirus infection  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Gastroenteritis  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Peritonsillar abscess  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Psoas abscess  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Sinusitis  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Urinary tract infection  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Viral infection  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Yersinia infection  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Injury, poisoning and procedural complications         
Brain contusion  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Contusion  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Femoral neck fracture  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Tibia fracture  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Aspartate aminotransferase increased  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Metabolism and nutrition disorders         
Hypercholesterolaemia  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Hyperglycaemia  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cervix carcinoma  1  1/204 (0.49%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Malignant melanoma  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Superficial spreading melanoma stage unspecified  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Nervous system disorders         
Cerebrovascular insufficiency  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Intracranial aneurysm  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Migraine  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Multiple sclerosis  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Multiple sclerosis relapse  1  44/204 (21.57%)  19/208 (9.13%)  18/209 (8.61%)  37/417 (8.87%) 
Syncope  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Temporal lobe epilepsy  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion missed  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Psychiatric disorders         
Mood disorder due to a general medical condition  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Renal and urinary disorders         
Nephrolithiasis  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Reproductive system and breast disorders         
Cervical dysplasia  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Dysfunctional uterine bleeding  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Endometrial hyperplasia  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Ovarian cyst  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Ovarian disorder  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Uterine polyp  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pleurisy  1  1/204 (0.49%)  0/208 (0.00%)  0/209 (0.00%)  0/417 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis allergic  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Dermatitis atopic  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Dermatitis exfoliative  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Erythema nodosum  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Rash  1  0/204 (0.00%)  1/208 (0.48%)  0/209 (0.00%)  1/417 (0.24%) 
Vascular disorders         
Circulatory collapse  1  0/204 (0.00%)  0/208 (0.00%)  1/209 (0.48%)  1/417 (0.24%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 150 mg DAC HYP 300 mg DAC HYP Total Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   128/204 (62.75%)   109/208 (52.40%)   111/209 (53.11%)   220/417 (52.76%) 
General disorders         
Pyrexia  1  2/204 (0.98%)  7/208 (3.37%)  15/209 (7.18%)  22/417 (5.28%) 
Infections and infestations         
Influenza  1  11/204 (5.39%)  5/208 (2.40%)  12/209 (5.74%)  17/417 (4.08%) 
Nasopharyngitis  1  31/204 (15.20%)  30/208 (14.42%)  30/209 (14.35%)  60/417 (14.39%) 
Oral herpes  1  10/204 (4.90%)  10/208 (4.81%)  13/209 (6.22%)  23/417 (5.52%) 
Pharyngitis  1  9/204 (4.41%)  13/208 (6.25%)  13/209 (6.22%)  26/417 (6.24%) 
Respiratory tract infection  1  11/204 (5.39%)  7/208 (3.37%)  13/209 (6.22%)  20/417 (4.80%) 
Upper respiratory tract infection  1  14/204 (6.86%)  18/208 (8.65%)  22/209 (10.53%)  40/417 (9.59%) 
Investigations         
Alanine aminotransferase increased  1  4/204 (1.96%)  9/208 (4.33%)  12/209 (5.74%)  21/417 (5.04%) 
Nervous system disorders         
Headache  1  21/204 (10.29%)  20/208 (9.62%)  20/209 (9.57%)  40/417 (9.59%) 
Multiple sclerosis relapse  1  73/204 (35.78%)  45/208 (21.63%)  38/209 (18.18%)  83/417 (19.90%) 
Psychiatric disorders         
Depression  1  3/204 (1.47%)  10/208 (4.81%)  12/209 (5.74%)  22/417 (5.28%) 
Skin and subcutaneous tissue disorders         
Rash  1  6/204 (2.94%)  11/208 (5.29%)  11/209 (5.26%)  22/417 (5.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Name/Title: Biogen Study Medical Director
Organization: Biogen
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00390221     History of Changes
Other Study ID Numbers: 205-MS-201
First Submitted: October 17, 2006
First Posted: October 19, 2006
Results First Submitted: May 31, 2016
Results First Posted: July 11, 2016
Last Update Posted: July 11, 2016