Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT00185211
Previous Study | Return to List | Next Study

BENEFIT Study (Betaferon® / Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) and BENEFIT Follow-up Study

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: NCT00185211
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : November 30, 2010
Last Update Posted : December 30, 2013
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Drug: Interferon beta-1b (Betaseron, BAY86-5046)
Enrollment 468
Recruitment Details  
Pre-assignment Details The full analysis set includes all 468 participants (particip.) with at least one administration of study drug in the placebo-controlled original study 92012, using treatment groups as randomized according to the minimization procedure regardless of the kind of study treatment (IFNB-1b/placebo) received. 19 subjects did not consent to the Follow-up
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Period Title: Placebo-controlled Study (92012)
Started 292 176
Completed 271 166
Not Completed 21 10
Reason Not Completed
Adverse Event             8             0
Lost to Follow-up             3             2
Withdrawal by Subject             9             7
fulfilled local def. and McDonald crit.             0             1
Adverse event, then subject's withdrawal             1             0
Period Title: Follow-up Study (91031 - This Study)
Started 261 [1] 157 [2]
Completed 235 123
Not Completed 26 34
Reason Not Completed
Adverse Event             5             6
Lack of Efficacy             1             0
Lost to Follow-up             6             4
Physician Decision             1             0
Pregnancy             0             1
Withdrawal by Subject             13             21
other disease modif. treatment             0             2
[1]
10 of the 271 subjects completing the placebo-controlled study did not consent to the Follow-up.
[2]
9 of the 166 subjects completing the placebo-controlled study did not consent to the Follow-up.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo Total
Hide Arm/Group Description Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial) Total of all reporting groups
Overall Number of Baseline Participants 292 176 468
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 292 participants 176 participants 468 participants
30.8  (7.6) 30.7  (7.1) 30.7  (7.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 292 participants 176 participants 468 participants
Female
207
  70.9%
124
  70.5%
331
  70.7%
Male
85
  29.1%
52
  29.5%
137
  29.3%
Number of T2 lesions detected in screening MRI (Magnet-Resonance Imaging)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 292 participants 176 participants 468 participants
2 to 4 T2 lesions 42 25 67
5 to 8 T2 lesions 43 28 71
at least 9 T2 lesions 207 123 330
[1]
Measure Description: Only patients with at least two clinically silent lesions on the T2-weighted brain MRI scan with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial, were included. Number of T2 lesions with the three categories was used in the minimization procedure.
Number of participants with steroid use during the first clinical demyelinating event   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 292 participants 176 participants 468 participants
Steroid Use 209 123 332
No Steroid Use 83 53 136
[1]
Measure Description: The allocation of participants to the treatment arms was according to a minimization procedure with an element of randomization to minimize imbalances of treatment groups with respect to e.g. steroid use during first clinical demyelinating event. Steroid treatment was at the discretion of the investigator.
Type of onset of disease (classification of first demyelinating event)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 292 participants 176 participants 468 participants
monofocal disease 153 93 246
multifocal disease 139 83 222
[1]
Measure Description: On the basis of the central classification of the patient’s symptoms and signs, the first event was classified as either monofocal (a single central nervous system (CNS) lesion suffices to explain the patient’s symptoms and signs) or multifocal (the patient’s symptoms and signs can only be explained by multiple (i.e. more than one) CNS lesions.
1.Primary Outcome
Title Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
Hide Description CDMS could be reached due to a qualifying relapse or sustained progression of 1.5 points on the expanded disability status scale (EDSS) as compared to the lowest EDSS obtained during screening or Day 1. The validity of CDMS diagnoses was confirmed by a central committee. The EDSS scale quantifies disability in MS in 8 functional systems, values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on an ordinal scale. Time to CDMS = date of CDMS - date of Day 1 + 1 or time to CDMS = date of last clinical visit - date of Day 1 + 1 (right-censored)
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intention to treat (ITT) principle. After five years, in the initial placebo arm 94 participants and in the initial IFNB-1b arm 124 participants had reached CDMS diagnosis.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 292 176
Measure Type: Number
Unit of Measure: cum. percentage of particip. with CDMS
Kaplan-Meier estimate at year 2 26.9 45.0
Kaplan-Meier estimate at year 3 36.7 51.2
Kaplan-Meier estimate at year 5 46.2 57.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments

The null hypothesis for comparison of initial IFNB-1b versus initial placebo treatment was:

H0: The survival functions (i.e., the probability that time to CDMS is ≥ t) are identical for both treatment arms for all points in time t>0.

The two-sided alternative hypothesis was:

H1: The survival functions (i.e., the probability that time to CDMS is ≥ t) are not identical for both treatment arms for some points in time t>0.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments A 2-sided error level of 0.0253 was used for analyses at month 36 and 60 in order to keep the study-wise error level at 0.05. A conditional sequential testing approach was used for the family of null hypotheses of the primary efficacy variables.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments Time to CDMS was modelled by a Cox proportional hazards regression model with the following covariates: treatment group, steroid use during first event (yes vs. no), onset of disease (monofocal vs. multifocal) and number of T2 lesions at screening (categories: 2-4, 5-8 and at least 9 T2 lesions). The null hypothesis was: Initial IFNB-1b and initial placebo do not differ with regard to the hazard for CDMS, i.e. hazard ratio = 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method Regression, Cox
Comments covariate adjustment: steroid use during first event, onset of disease, categorized number of T2 lesions at screening
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.663
Confidence Interval 97.47%
0.488 to 0.902
Estimation Comments The direction of comparison is initial IFNB-1b (numerator) versus initial placebo (denominator), i.e. the Hazard Ratio represents the relative risk of initial IFNB-1b treatment compared to initial placebo treatment.
2.Primary Outcome
Title Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
Hide Description EDSS progression was defined as an increase in the expanded disability status scale (EDSS) of 1.0 point compared to the lowest EDSS score obtained during the screening or baseline visit, if this score was <= 5.5. A confirmed EDSS progression status was defined as an EDSS progression observed at two consecutive scheduled visits at least 140 days apart from each other. The EDSS scale is a method of quantifying disability in multiple sclerosis in eight functional systems and values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on a scale.
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. The 25%-percentile for time to confirmed EDSS progression was 908 days in the initial placebo arm but was not estimable in the initial IFNB-1b arm. After five years, in the initial placebo arm 47 participants and in the initial IFNB-1b arm 65 participants had reached confirmed EDSS progression.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 292 176
Measure Type: Number
Unit of Measure: percentage of particip. with EDSS progr.
Kaplan-Meier estimate at year 2 12.8 19.9
Kaplan-Meier estimate at year 3 16.8 25.3
Kaplan-Meier estimate at year 5 24.9 28.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis for comparison of initial IFNB-1b versus initial placebo treatment was: H0: The survival functions (i.e., the probability that time to confirmed EDSS progression is ≥ t) are not identical for both treatment arms for some points in time t>0. The two-sided alternative hypothesis was: H1: The survival functions (i.e., the probability that time to confirmed EDSS progression is ≥ t) are identical for both treatment arms for some points in time t>0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1768
Comments A 2-sided error level of 0.0253 was used for analyses at month 36 and 60 in order to keep the study-wise error level at 0.05. A conditional sequential testing approach was used for the family of null hypotheses of the primary efficacy variables.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments Time to confirmed EDSS progression was modelled by a Cox proportional hazards regression model with the following covariates: treatment group and volume of T2 lesions on screening MRI. The null hypothesis was: Initial IFNB-1b and initial placebo do not differ with regard to the hazard for confirmed EDSS progression, i.e. hazard ratio = 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1604
Comments [Not Specified]
Method Regression, Cox
Comments The variable used as additional covariate adjustment was volume of T2 lesions on screening MRI.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.764
Confidence Interval 97.47%
0.497 to 1.174
Estimation Comments The direction of comparison is initial IFNB-1b (numerator) versus initial placebo (denominator), i.e. the Hazard Ratio represents the relative risk of initial IFNB-1b treatment compared to initial placebo treatment.
3.Primary Outcome
Title Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60
Hide Description As an index of health related quality of life in people diagnosed with MS, the FAMS Trial Outcome Index covers overall physical health (sum of sub-scale scores Mobility, Symptoms, Thinking/Fatigue, Additional Concerns) with a score range from 0 to 148. A higher score reflects a higher overall physical health as reported by patients.
Time Frame 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all patients who completed the follow-up study could be included at month 60 as subject to copyright constraints and to the availability of validated language versions, FAMS assessments could not be conducted in all patients.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 169 91
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
125
(107 to 139)
125
(104.83 to 140)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of FAMS TOI at month 60, adjusted for baseline FAMS TOI, is identical for both treatment arms” was tested against the alternative hypothesis HA: “The distribution of FAMS TOI at month 60, adjusted for baseline FAMS TOI, is not the same in the two treatment arms” using a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8880
Comments A 2-sided error level of 0.0253 was used for analyses at month 36 and 60 in order to keep the study-wise error level at 0.05. A conditional sequential testing approach was used for the family of null hypotheses of the primary efficacy variables.
Method non-parametric ANCOVA
Comments Variable used as covariate: FAMS TOI measured at baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The mean FAMS TOI at month 60, adjusted for baseline FAMS TOI, is identical for both treatment arms” was tested against the alternative hypothesis HA: “The mean FAMS TOI at month 60, adjusted for baseline FAMS TOI, is not the same in the two treatment arms” using a parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3832
Comments [Not Specified]
Method ANCOVA
Comments Variable used as covariate: FAMS TOI measured at baseline
4.Secondary Outcome
Title Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria
Hide Description MS according to the criteria by McDonald was reached if, in addition to the single clinical demyelinating event, both dissemination in space and dissemination in time were established by MRI-criteria or a new relapse. Time to McDonald MS is the difference of date of McDonald MS to the date of Day 1 + 1. For subjects without McDonald MS, time to McDonald MS is the difference from the maximum (date of last magnetic resonance imaging scan, date of last clinical visit) to the date of Day 1 + 1 (right-censored observation).
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. After five years, in the initial placebo arm 151 participants and in the initial IFNB-1b arm 224 participants had reached McDonald MS diagnosis.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 292 176
Median (95% Confidence Interval)
Unit of Measure: months
9.4
(8.8 to 12.1)
6
(4.8 to 6.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments

The null hypothesis for comparison of initial IFNB-1b versus initial placebo treatment was:

H0: The survival functions (i.e., the probability that time to McDonald MS is ≥ t) are identical for both treatment arms for all points in time t>0.

The two-sided alternative hypothesis was:

H1: The survival functions (i.e., the probability that time to McDonald MS is ≥ t) are not identical for both treatment arms for some points in time t>0.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000006
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments Time to McDonald MS was modelled by a Cox proportional hazards regression model with the following covariates: treatment group, steroid use during first event (yes vs. no), onset of disease (monofocal vs. multifocal) and number of T2 lesions at screening (categories: 2-4, 5-8 and at least 9 T2 lesions). The null hypothesis was: Initial IFNB-1b and initial placebo do not differ with regard to the hazard for McDonald MS, i.e. hazard ratio = 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.000001
Comments [Not Specified]
Method Regression, Cox
Comments covariate adjustment: steroid use during first event, onset of disease, categorized number of T2 lesions at screening
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.583
Confidence Interval 95%
0.474 to 0.718
Estimation Comments The direction of comparison is initial IFNB-1b versus initial placebo, i.e. the Hazard Ratio represents the relative risk of initial IFNB-1b treatment compared to initial placebo treatment.
5.Secondary Outcome
Title Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses
Hide Description A relapse was defined as the appearance of a new neurological abnormality or the reappearance of a neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The time to the onset of recurrent relapses was determined for each subject according to the counting process representation for recurrent events. Time to a relapse was right-censored if a relapse-risk period ended without relapse. Based on the Andersen-Gill model the hazard ratio for recurrent relapses was estimated. Annualized relapse rates are provided as another outcome measure.
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the Intention-To-Treat (ITT) principle. The hazard for recurrent relapses was modelled by an extension of the Cox Proportional Hazards (PH) regression model (Andersen-Gill Model).
Arm/Group Title All Subjects
Hide Arm/Group Description:
All subjects part of Intention-To-Treat (ITT) Population
Overall Number of Participants Analyzed 468
Measure Type: Number
Unit of Measure: Ratio
0.797
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Subjects
Comments The time to recurrent relapses was modelled by an extension of Cox's PH regression model (Andersen-Gill Model) for recurrent events with the following covariates: treatment group, steroid use during first event (yes vs. no), onset of disease (monofocal vs. multifocal) and number of T2 lesions at screening (2-4, 5-8 and at least 9 T2 lesions). The null hypothesis was: Initial IFNB-1b and initial placebo do not differ with regard to the hazard for recurrent relapses, i.e. hazard ratio = 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1265
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method Andersen-Gill Model
Comments Covariate adjustment: steroid use during first event, onset of disease, categorized number of T2 lesions at screening
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.797
Confidence Interval 95%
0.595 to 1.066
Estimation Comments The direction of comparison is initial IFNB-1b (numerator) versus initial placebo (denominator), i.e. the Hazard Ratio represents the relative risk of initial IFNB-1b treatment compared to initial placebo treatment.
6.Secondary Outcome
Title Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate
Hide Description The annualized relapse rate is defined as total number of relapses up to month 60 divided by the total observation time (last clinical visit minus first day of study treatment administration plus 1 of all participants) in years.
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. For each treatment arm, the relapse rate is defined as total number of relapses up to month 60 divided by the total observation time in years.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 292 176
Mean (95% Confidence Interval)
Unit of Measure: number of relapses per patient and year
0.2139
(0.1895 to 0.2406)
0.2695
(0.2337 to 0.3093)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments Relapse rate was analyzed by a generalized linear Poisson regression model with individual relapse counts as dependent variable, covariates: treatment arm, steroid use during first event, onset of disease and categorized number of T2 lesions at screening and offset variable natural log of time (in years) as difference between last clinical visit and baseline visit. The treatment effect on the relapse rate was of primary interest.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0141
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method generalized linear Poisson regression
Comments covariate adjustment: steroid use during first event, onset of disease, categorized number of T2 lesions at screening
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7971
Confidence Interval 95%
0.6650 to 0.9554
Estimation Comments The direction of comparison is initial IFNB-1b (numerator) versus initial placebo (denominator), i.e. the Risk Ratio represents the relative risk of initial IFNB-1b treatment compared to initial placebo treatment.
7.Secondary Outcome
Title Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60
Hide Description The MSFC score consists of three sub-tests (Timed-25-Foot-Walk, 9-Hole-Peg-Test, 3" Paced Auditory Serial Addition Test [PASAT]). Standardized results (Z-scores) of the sub-tests and the overall MSFC Z-score as an average of the three Z-scores were derived using baseline data pooled over both treatment arms as reference population. Higher Z-scores reflect a better neurological status.
Time Frame 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MSFC results at month 60 available.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 228 120
Median (Inter-Quartile Range)
Unit of Measure: Z-scores
0.226
(-0.163 to 0.502)
0.225
(-0.207 to 0.619)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of MSFC Z-scores at month 60 adjusted for baseline MSFC Z-score is identical for both treatment arms” was tested against the alternative hypothesis HA: “The distribution of MSFC Z-scores at month 60 adjusted for baseline MSFC Z-score is not the same in the two treatment groups” based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6078
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method non-parametric ANCOVA
Comments Variable used as covariate: MSFC Z-scores measured at baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The mean MSFC Z-scores at month 60 adjusted for baseline MSFC Z-score are identical for both treatment arms” was tested against the alternative hypothesis HA: “The mean MSFC Z-scores at month 60 adjusted for baseline MSFC Z-score are not the same in the two treatment groups” based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8245
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method ANCOVA
Comments Variable used as covariate: MSFC Z-scores measured at baseline
8.Secondary Outcome
Title MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60
Hide Description Newly active lesions are defined as displaying either new Gadolinium (Gd)-enhancement on T1-weighted scans or non-enhancement on T1-weighted scan but new on T2-weighted scan. The numbers of newly active lesions on yearly MRI scans were summed up to the cumulative number.
Time Frame up to 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all patients in the full analysis set completed the follow-up study or had MRI scan readings at month 60 available.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 219 114
Median (Inter-Quartile Range)
Unit of Measure: cumulative number of lesions
4
(1 to 12)
7
(2 to 18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of the cumulative number of newly active lesions at month 60 adjusted for the number of Gadolinium (Gd)-enhancing lesions on T1 at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method non-parametric ANCOVA
Comments Variable used as covariate: number of Gd-enhancing lesions on T1 at screening
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments Assuming that the cumulative number of newly active lesions at month 60 follows a negative binomial distribution, a generalized linear model (logarithmic link function, covariate: number of Gd-enhancing lesions on T1 at BENEFIT screening) was set up in order to analyze the treatment effect on that MRI outcome.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0435
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method generalized linear model
Comments Distribution: negative binomial distribution; covariate: number of Gd-enhancing lesions on T1 at screening
Method of Estimation Estimation Parameter Relative effect size
Estimated Value 0.7351
Confidence Interval 95%
0.5436 to 0.9940
Estimation Comments The direction of comparison is initial IFNB-1b versus initial placebo.
9.Secondary Outcome
Title MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60
Hide Description Absolute change of T2 lesion volume from screening MRI to month 60 was calculated as T2 lesion volume at month 60 minus T2 lesion volume at screening.
Time Frame 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MRI scan readings at month 60 available.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 215 112
Median (Inter-Quartile Range)
Unit of Measure: cubic millimeter
-123.0
(-849.0 to 240.0)
-194.5
(-657.5 to 367.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of the absolute change of T2 lesion volume at month 60 adjusted for the T2 lesion volume at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7801
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method non-parametric ANCOVA
Comments Variable used as covariate: T2 lesion volume at screening
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The mean absolute change of T2 lesion volume at month 60 adjusted for the T2 lesion volume at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9408
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method ANCOVA
Comments Variable used as covariate: T2 lesion volume at screening
10.Secondary Outcome
Title MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60
Hide Description Absolute change of volume of black holes from screening MRI to month 60 was calculated as volume of black holes at month 60 minus volume of black holes at screening.
Time Frame 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all FAS patients completed the follow-up study or had MRI scan readings at month 60 available.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 217 114
Median (Inter-Quartile Range)
Unit of Measure: cubic millimeter
0
(-169 to 40)
0
(-94 to 54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of the absolute change of volume of black holes at month 60 adjusted for the volume of black holes at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6619
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method non-parametric ANCOVA
Comments Variable used as covariate: Volume of black holes at screening
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The mean absolute change of volume of black holes at month 60 adjusted for the volume of black holes at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8558
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method ANCOVA
Comments Variable used as covariate: Volume of black holes at screening
11.Secondary Outcome
Title MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60
Hide Description Two-timepoint percentage brain volume change was estimated with Structural Image Evaluation, using Normalisation, of Atrophy (SIENA) software. The measurements describe the percentage change from screening in brain volume at month 60.
Time Frame 60 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the ITT principle. Not all patients in the full analysis set completed the follow-up study or had MRI scan readings at month 60 available. There were several missing values in both treatment arms regarding the percentage brain volume change.
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description:
Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Overall Number of Participants Analyzed 141 80
Median (Inter-Quartile Range)
Unit of Measure: Percentage of brain volume
-2.281
(-3.672 to -1.062)
-1.771
(-3.294 to -0.667)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The distribution of the percentage change of brain volume at month 60 adjusted for the brain volume at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a non-parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1208
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method non-parametric ANCOVA
Comments Variable used as covariate: Brain volume at screening
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Initial IFNB-1b (Interferon Beta-1b), Initial Placebo
Comments The null hypothesis H0: “The mean percentage change of brain volume at month 60 adjusted for the brain volume at screening is identical for both treatment arms.” was tested against the corresponding two-sided alternative hypothesis based on a parametric analysis of covariance (ANCOVA).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0719
Comments The two-sided error level for the exploratory analysis of the secondary outcome measures was of 0.05.
Method ANCOVA
Comments Variable used as covariate: Brain volume at screening
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Hide Arm/Group Description Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
All-Cause Mortality
Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   61/292 (20.89%)   42/176 (23.86%) 
Blood and lymphatic system disorders     
Leukopenia * 1  1/292 (0.34%)  0/176 (0.00%) 
Cardiac disorders     
Myocardial infarct * 1  1/292 (0.34%)  0/176 (0.00%) 
Cardiovascular disorder * 1  0/292 (0.00%)  1/176 (0.57%) 
Endocrine disorders     
Goiter * 1  0/292 (0.00%)  1/176 (0.57%) 
Eye disorders     
Eye disorder * 1  0/292 (0.00%)  1/176 (0.57%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/292 (0.00%)  1/176 (0.57%) 
Colitis * 1  1/292 (0.34%)  2/176 (1.14%) 
Gastrointestinal Disorder * 1  1/292 (0.34%)  0/176 (0.00%) 
Gastrointestinal Hemorrhage * 1  0/292 (0.00%)  1/176 (0.57%) 
Nausea * 1  0/292 (0.00%)  1/176 (0.57%) 
General disorders     
Cyst * 1  1/292 (0.34%)  0/176 (0.00%) 
Fever * 1  0/292 (0.00%)  1/176 (0.57%) 
Hernia * 1  0/292 (0.00%)  1/176 (0.57%) 
Mucous membrane disorder * 1  1/292 (0.34%)  0/176 (0.00%) 
Unevaluable reaction * 1  10/292 (3.42%)  8/176 (4.55%) 
Injection site necrosis * 1  2/292 (0.68%)  0/176 (0.00%) 
Injection site reaction * 1  1/292 (0.34%)  0/176 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/292 (0.34%)  0/176 (0.00%) 
Hepatitis * 1  1/292 (0.34%)  0/176 (0.00%) 
Jaundice * 1  1/292 (0.34%)  0/176 (0.00%) 
Immune system disorders     
Allergic reaction * 1  1/292 (0.34%)  0/176 (0.00%) 
Infections and infestations     
Cellulitis * 1  0/292 (0.00%)  1/176 (0.57%) 
Infection * 1  0/292 (0.00%)  1/176 (0.57%) 
Pneumonia * 1  1/292 (0.34%)  1/176 (0.57%) 
Pharyngitis * 1  1/292 (0.34%)  0/176 (0.00%) 
Sinusitis * 1  1/292 (0.34%)  2/176 (1.14%) 
Cystitis * 1  1/292 (0.34%)  0/176 (0.00%) 
Urinary tract infection * 1  0/292 (0.00%)  1/176 (0.57%) 
Pyelonephritis * 1  1/292 (0.34%)  0/176 (0.00%) 
Injury, poisoning and procedural complications     
Accidental injury * 1  3/292 (1.03%)  1/176 (0.57%) 
Bone fracture (not spontaneous) * 1  3/292 (1.03%)  1/176 (0.57%) 
Investigations     
Liver function test abnormal * 1  2/292 (0.68%)  0/176 (0.00%) 
Weight gain * 1  1/292 (0.34%)  0/176 (0.00%) 
Metabolism and nutrition disorders     
Hyponatremia * 1  1/292 (0.34%)  0/176 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  3/292 (1.03%)  0/176 (0.00%) 
Arthralgia * 1  1/292 (0.34%)  0/176 (0.00%) 
Tendon disorder * 1  0/292 (0.00%)  1/176 (0.57%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm * 1  1/292 (0.34%)  0/176 (0.00%) 
Thyroid carcinoma * 1  0/292 (0.00%)  1/176 (0.57%) 
Breast carcinoma * 1  1/292 (0.34%)  0/176 (0.00%) 
Breast neoplasm * 1  0/292 (0.00%)  1/176 (0.57%) 
Nervous system disorders     
Migraine * 1  0/292 (0.00%)  1/176 (0.57%) 
Convulsion * 1  0/292 (0.00%)  1/176 (0.57%) 
Grand mal convulsion * 1  0/292 (0.00%)  1/176 (0.57%) 
Myoclonus * 1  1/292 (0.34%)  0/176 (0.00%) 
Headache * 1  0/292 (0.00%)  1/176 (0.57%) 
Multiple sclerosis * 1  11/292 (3.77%)  5/176 (2.84%) 
Pregnancy, puerperium and perinatal conditions     
Abortion * 1  1/292 (0.34%)  1/176 (0.57%) 
Unintended pregnancy * 1  0/292 (0.00%)  1/176 (0.57%) 
Psychiatric disorders     
Suicide attemp other than overdose * 1  0/292 (0.00%)  1/176 (0.57%) 
Anxiety * 1  0/292 (0.00%)  1/176 (0.57%) 
Depression * 1  2/292 (0.68%)  2/176 (1.14%) 
Emotional lability * 1  0/292 (0.00%)  1/176 (0.57%) 
Personality disorder * 1  0/292 (0.00%)  1/176 (0.57%) 
Psychosis * 1  1/292 (0.34%)  0/176 (0.00%) 
Psychotic depression * 1  1/292 (0.34%)  0/176 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst * 1  0/292 (0.00%)  2/176 (1.14%) 
Endometrial disorder * 1  0/292 (0.00%)  1/176 (0.57%) 
Vaginal hemorrhage * 1  1/292 (0.34%)  0/176 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  0/292 (0.00%)  1/176 (0.57%) 
Epistaxis * 1  1/292 (0.34%)  0/176 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin necrosis * 1  0/292 (0.00%)  1/176 (0.57%) 
Skin ulcer * 1  1/292 (0.34%)  0/176 (0.00%) 
Surgical and medical procedures     
Surgery * 1  12/292 (4.11%)  6/176 (3.41%) 
Vascular disorders     
Thrombosis * 1  0/292 (0.00%)  1/176 (0.57%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, Harts 2.3
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Initial IFNB-1b (Interferon Beta-1b) Initial Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   283/292 (96.92%)   169/176 (96.02%) 
Blood and lymphatic system disorders     
Leukopenia * 1  73/292 (25.00%)  26/176 (14.77%) 
Ear and labyrinth disorders     
Vertigo * 1  10/292 (3.42%)  10/176 (5.68%) 
Eye disorders     
Eye pain * 1  18/292 (6.16%)  7/176 (3.98%) 
Abnormal vision * 1  17/292 (5.82%)  8/176 (4.55%) 
Blurred vision * 1  17/292 (5.82%)  4/176 (2.27%) 
Gastrointestinal disorders     
Abdominal pain * 1  22/292 (7.53%)  14/176 (7.95%) 
Tooth disorder * 1  19/292 (6.51%)  9/176 (5.11%) 
Diarrhea * 1  21/292 (7.19%)  9/176 (5.11%) 
Nausea * 1  21/292 (7.19%)  10/176 (5.68%) 
Vomiting * 1  23/292 (7.88%)  7/176 (3.98%) 
General disorders     
Asthenia * 1  89/292 (30.48%)  53/176 (30.11%) 
Fever * 1  48/292 (16.44%)  18/176 (10.23%) 
Pain * 1  36/292 (12.33%)  15/176 (8.52%) 
Injection site reaction * 1  163/292 (55.82%)  71/176 (40.34%) 
Chills * 1  17/292 (5.82%)  5/176 (2.84%) 
Injection site pain * 1  24/292 (8.22%)  9/176 (5.11%) 
Hepatobiliary disorders     
Bilirubinemia * 1  29/292 (9.93%)  20/176 (11.36%) 
Immune system disorders     
Allergic reaction * 1  23/292 (7.88%)  11/176 (6.25%) 
Infections and infestations     
Flu syndrome * 1  152/292 (52.05%)  90/176 (51.14%) 
Upper respiratory infection * 1  96/292 (32.88%)  59/176 (33.52%) 
Pharyngitis * 1  47/292 (16.10%)  26/176 (14.77%) 
Infection * 1  29/292 (9.93%)  11/176 (6.25%) 
Gastroenteritis * 1  19/292 (6.51%)  14/176 (7.95%) 
Bronchitis * 1  27/292 (9.25%)  15/176 (8.52%) 
Rhinitis * 1  18/292 (6.16%)  9/176 (5.11%) 
Sinusitis * 1  19/292 (6.51%)  16/176 (9.09%) 
Urinary tract infection * 1  14/292 (4.79%)  13/176 (7.39%) 
Injury, poisoning and procedural complications     
Accidental injury * 1  26/292 (8.90%)  14/176 (7.95%) 
Investigations     
SGOT increased * 1  34/292 (11.64%)  7/176 (3.98%) 
SGPT increased * 1  50/292 (17.12%)  14/176 (7.95%) 
Liver function test abnormal * 1  19/292 (6.51%)  6/176 (3.41%) 
Metabolism and nutrition disorders     
Hyperglycemia * 1  12/292 (4.11%)  11/176 (6.25%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  49/292 (16.78%)  20/176 (11.36%) 
Pain in extremity * 1  33/292 (11.30%)  15/176 (8.52%) 
Myalgia * 1  29/292 (9.93%)  20/176 (11.36%) 
Neck pain * 1  11/292 (3.77%)  9/176 (5.11%) 
Arthralgia * 1  21/292 (7.19%)  15/176 (8.52%) 
Muscle cramps * 1  15/292 (5.14%)  8/176 (4.55%) 
Myasthenia * 1  16/292 (5.48%)  10/176 (5.68%) 
Nervous system disorders     
Headache * 1  98/292 (33.56%)  54/176 (30.68%) 
Multiple sclerosis * 1  112/292 (38.36%)  82/176 (46.59%) 
Paresthesia * 1  82/292 (28.08%)  53/176 (30.11%) 
Dizziness * 1  14/292 (4.79%)  10/176 (5.68%) 
Hypertonia * 1  15/292 (5.14%)  5/176 (2.84%) 
Hypesthesia * 1  15/292 (5.14%)  10/176 (5.68%) 
Pregnancy, puerperium and perinatal conditions     
Unintended pregnancy * 1  15/292 (5.14%)  12/176 (6.82%) 
Psychiatric disorders     
Anxiety * 1  33/292 (11.30%)  18/176 (10.23%) 
Depression * 1  56/292 (19.18%)  41/176 (23.30%) 
Insomnia * 1  37/292 (12.67%)  21/176 (11.93%) 
Respiratory, thoracic and mediastinal disorders     
Sore throat * 1  19/292 (6.51%)  11/176 (6.25%) 
Skin and subcutaneous tissue disorders     
Rash * 1  39/292 (13.36%)  15/176 (8.52%) 
Surgical and medical procedures     
Surgery * 1  22/292 (7.53%)  14/176 (7.95%) 
Vascular disorders     
Hypertension * 1  13/292 (4.45%)  9/176 (5.11%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, Harts 2.3
Participant Flow: Subject with "Other" as reason for not completing a study period are presented according to the NIH pre-specified categories as far as possible.
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.
Submit for review any manuscript / abstract related to the Study at least 90 days prior to publication.The proposed publication / presentation shall only be made after BSP has obtained adequate patent protection for the Results, or after the patentable information has been taken out of the publication/presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: BAYER
EMail: clinical-trials-contact@bayerhealthcare.com
Publications of Results:
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00185211     History of Changes
Other Study ID Numbers: 91031
305207 ( Other Identifier: Company Internal )
First Submitted: September 9, 2005
First Posted: September 16, 2005
Results First Submitted: July 23, 2009
Results First Posted: November 30, 2010
Last Update Posted: December 30, 2013