Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   40977   clinical trials with a EudraCT protocol, of which   6698   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A long-term follow-up study for Multiple Sclerosis patients who have completed the alemtuzumab Extension Study (CAMMS03409)

    Summary
    EudraCT number
    2013-003884-71
    Trial protocol
    BE   NL   CZ   ES   DE   IT   DK   HR  
    Global end of trial date
    15 Jul 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    26 Jul 2021
    First version publication date
    26 Jul 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    LPS13649
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02255656
    WHO universal trial number (UTN)
    U1111-1148-2987
    Sponsors
    Sponsor organisation name
    Genzyme Corporation, a Sanofi company
    Sponsor organisation address
    50 Binney St., Cambridge, Massachusetts, United States, 02142
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Aug 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate long-term safety of alemtuzumab.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Jan 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 7
    Country: Number of subjects enrolled
    Australia: 43
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Poland: 53
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    United Kingdom: 81
    Country: Number of subjects enrolled
    Croatia: 111
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Czechia: 27
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Germany: 38
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Brazil: 29
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Russian Federation: 136
    Country: Number of subjects enrolled
    Ukraine: 57
    Country: Number of subjects enrolled
    United States: 347
    Country: Number of subjects enrolled
    Mexico: 13
    Country: Number of subjects enrolled
    Canada: 29
    Country: Number of subjects enrolled
    Serbia: 49
    Worldwide total number of subjects
    1062
    EEA total number of subjects
    266
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1061
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 142 study centres in 21 countries. A total of 1062 subjects were screened between 7 January 2015 and 28 June 2016 and were enrolled in current study (LPS13649 [TOPAZ]).

    Pre-assignment
    Screening details
    Subgroup analysis (DAT subgroup and IAT subgroup) performed only for end-points and safety analysis. Subjects rolled over from CAMMS223 (NCT00050778) to CAMMS03409 (NCT00930553), then subsequently enrolled and took 24 mg alemtuzumab in CAMMS324 (NCT00548405) study, were not considered as part of DAT/IAT subgroup and included in overall group.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Alemtuzumab
    Arm description
    All Subjects who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Subjects received alemtuzumab, intravenous infusion of 12 milligrams per day (mg/day) for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
    Arm type
    Experimental

    Investigational medicinal product name
    Alemtuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Number of subjects in period 1
    Alemtuzumab
    Started
    1062
    Completed
    592
    Not completed
    470
         Poor compliance to protocol
    3
         Due to Coronavirus Disease (Covid-19)
    300
         Unspecified
    126
         Adverse Event
    11
         Lost to follow-up
    30

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    All Subjects who completed the study CAMM03409 (extension study of CAMMS223 [NCT00050778],CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Subjects received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Reporting group values
    Overall Study Total
    Number of subjects
    1062 1062
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    41.2 ± 8.6 -
    Gender categorical
    Units: Subjects
        Female
    686 686
        Male
    376 376
    Race/Ethnicity
    Units: Subjects
        White
    988 988
        Black or African American
    34 34
        Asian
    5 5
        American Indian or Alaska native
    6 6
        Other
    29 29

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Alemtuzumab
    Reporting group description
    All Subjects who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Subjects received alemtuzumab, intravenous infusion of 12 milligrams per day (mg/day) for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Subject analysis set title
    Delayed Alemtuzumab Treatment (DAT)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from the subcutaneous interferon beta-1a (SC IFNB1a) treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Subjects received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Subject analysis set title
    Initial Alemtuzumab Treatment (IAT)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Subjects received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Primary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs)

    Close Top of page
    End point title
    Number of Subjects With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) [1]
    End point description
    An Adverse Event (AE) was any untoward medical occurrence in a subject administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed/worsened during the ‘treatment period (time from Baseline until the end of the study LPS13649 [i.e. up to a maximum of 5.6 years]). Serious AE (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Analysis was performed on safety analysis set that included all subjects who signed the informed consent form (ICF). As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Primary
    End point timeframe
    From Baseline until the end of the study (up to a maximum duration of 5.6 years)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1062
    241
    598
    Units: subjects
        Any TEAE
    879
    204
    500
        Any TESAE
    237
    55
    133
        Any TEAE leading to death
    11
    0
    10
        Any TEAE led permanent treatment discontinuation
    2
    0
    2
    No statistical analyses for this end point

    Primary: Number of Subjects With Infusion-Associated Reactions (IAR)

    Close Top of page
    End point title
    Number of Subjects With Infusion-Associated Reactions (IAR) [2]
    End point description
    IAR was defined as any AE occurring during and within 24 hours of alemtuzumab infusion. Analysis was performed on re-treated population that included all subjects who have signed the ICF and who had received study drug in the current study LPS13649. Here, ‘number of subject analysed’ = subjects evaluable for this endpoint. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Primary
    End point timeframe
    Within 24 hours of any alemtuzumab infusion
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    294
    83
    164
    Units: subjects
    164
    48
    89
    No statistical analyses for this end point

    Primary: Number of Subjects With Adverse Events of Special Interest (AESI)

    Close Top of page
    End point title
    Number of Subjects With Adverse Events of Special Interest (AESI) [3]
    End point description
    AESI included the following: hypersensitivity or anaphylaxis; pregnancy of a woman entered in the study; symptomatic overdose (serious or non-serious) with investigational medicinal product (IMP); increase in alanine transaminase (ALT); autoimmune mediated conditions; hemophagocytic lymphohistiocytosis; progressive multifocal leukoencephalopathy; temporally associated AEs; serious infections; malignancy; and pneumonitis. Analysis was performed on safety population. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Primary
    End point timeframe
    From Baseline until the end of the study (up to a maximum duration of 5.6 years)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1062
    241
    598
    Units: subjects
        Hypersensitivity or anaphylaxis
    44
    12
    25
        Pregnancy of a woman entered in the study
    70
    17
    42
        Symptomatic overdose (serious/non-serious)with IMP
    0
    0
    0
        Increase in ALT
    1
    0
    0
        Autoimmune mediated conditions
    100
    27
    66
        Hemophagocytic lymphohistiocytosis
    0
    0
    0
        Progressive multifocal leukoencephalopathy
    0
    0
    0
        Temporally associated AEs
    9
    2
    4
        Serious infections
    60
    10
    35
        Malignancy
    27
    6
    15
        Pneumonitis
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities

    Close Top of page
    End point title
    Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities [4]
    End point description
    Criteria for potentially clinically significant laboratory abnormalities included: • Hemoglobin (Hb): less than or equal to (<=)115 grams per liter (g/L)(Male [M]), <= 95 g/L (Female[ F]); greater than or equal to (>=)185 g/L (M), >= 165 g/L (F); Decrease From Baseline (DFB) >= 20 g/L. • Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). • RBCs: >=6 *10^12/L. •Platelets: <100 *10^9/L; >=700 *10^9/L. Analysis was performed on all subjects who have signed the ICF; and received study drug in the TOPAZ study; or in studies CAMMS223,CAMMS323,CAMMS324 or CAMMS03409, and did not complete 48 months of follow-up at the screening visit in the TOPAZ study. Here, ‘number of subjects analysed’=subjects evaluable for this endpoint and ‘n’ = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Primary
    End point timeframe
    From Baseline until the end of the study (up to a maximum duration of 5.6 years)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    619
    214
    316
    Units: subjects
        Hb:<=115 g/L, <=95 g/L(n=619,214,316)
    43
    11
    28
        Hb: >=185 g/L, >=165 g/L(n=619,214,316)
    12
    2
    6
        Hb: DFB >=20 g/L (n=580,206,293)
    98
    32
    50
        Hematocrit: <= 0.37 v/v; <=0.32 v/v(n=617,213,315)
    70
    20
    42
        Hematocrit: >=0.55 v/v; >=0.5 v/v(n=617,213,315)
    26
    6
    14
        RBCs: >=6 *10^12/L(n=618,214,315)
    21
    8
    7
        Platelets: <100 *10^9/L(n=615,212,314)
    25
    5
    16
        Platelets: >=700 *10^9/L(n=615,212,314)
    1
    1
    0
    No statistical analyses for this end point

    Secondary: Annualised Relapse Rate

    Close Top of page
    End point title
    Annualised Relapse Rate
    End point description
    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Annualised relapse rate was obtained from the total number of confirmed relapses that occurred during the treatment follow up time of all subjects divided by the total years of follow-up for all subjects. The annualised relapse rate was estimated using a negative binomial model with robust variance estimation. Analysis was performed on efficacy population which included all enrolled subjects who received study drug in studies CAMMS223, CAMMS323, CAMMS324 or CAMMS03409. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Up to a maximum duration of 5.6 years
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: relapses per subject per year
        number (confidence interval 95%)
    0.1994 (0.1710 to 0.2325)
    0.1608 (0.1418 to 0.1823)
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Were Relapse Free

    Close Top of page
    End point title
    Proportion of Subjects Who Were Relapse Free
    End point description
    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. The proportion of subjects who were relapse free (without event) were estimated using the Kaplan-Meier method. Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Up to a maximum duration of 5.6 years
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: proportion of subjects
        number (confidence interval 95%)
    29.59 (23.73 to 35.65)
    36.86 (32.96 to 40.76)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36,42, 48, 54 and 60

    Close Top of page
    End point title
    Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36,42, 48, 54 and 60
    End point description
    EDSS is an ordinal scale in half-point increments that qualifies disability in subjects with multiple sclerosis (MS). It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes. Analysis was performed on efficacy population. Here, ‘n’ = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36,42, 48, 54 and 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: score on a scale
    least squares mean (standard error)
        Month 6 (n=237,583)
    0.21 ± 0.092
    0.03 ± 0.065
        Month 12 (n=234,580)
    0.27 ± 0.093
    0.08 ± 0.065
        Month 18 (n=226,562)
    0.29 ± 0.096
    0.10 ± 0.067
        Month 24 (n=227,559)
    0.28 ± 0.102
    0.15 ± 0.070
        Month 30 (n=225,547)
    0.34 ± 0.102
    0.16 ± 0.071
        Month 36 (n=219,545)
    0.38 ± 0.103
    0.18 ± 0.071
        Month 42 (n=217,515)
    0.37 ± 0.103
    0.24 ± 0.071
        Month 48 (n=204,468)
    0.46 ± 0.104
    0.27 ± 0.072
        Month 54 (n=168,346)
    0.51 ± 0.106
    0.30 ± 0.074
        Month 60 (n=55,125)
    0.43 ± 0.129
    0.32 ± 0.088
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan
    End point description
    Number of Gd-enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with generalised estimating equation (GEE) adjusted for analysis groups and geographic region as covariates. Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Up to a maximum duration of 5.6 years
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: lesions per scan
        number (confidence interval 95%)
    1.307 (0.880 to 1.941)
    1.558 (1.153 to 2.105)
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
    End point description
    Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates. Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Up to a maximum duration of 5.6 years
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: lesions per scan
        number (confidence interval 95%)
    8.033 (6.001 to 10.753)
    9.564 (7.656 to 11.946)
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan
    End point description
    Number of new T1 lesions per scan was defined as the total number of new T1 lesion (and New Hypointense T1) that occurred during treatment period divided by the total number of scans performed during treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Up to a maximum duration of 5.6 years
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: lesions per scan
        number (confidence interval 95%)
    1.719 (1.141 to 2.589)
    1.908 (1.386 to 2.628)
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48 and 60
    End point description
    The total lesion volume (T1 lesions) was measured by MRI scan. Analysis was preformed on efficacy population. Here, ‘n’ = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: percent change
    arithmetic mean (standard deviation)
        Month 12 (n=203,501)
    141.71 ± 449.79
    64.73 ± 241.92
        Month 24 (n=202,489)
    130.73 ± 398.65
    67.48 ± 262.64
        Month 36 (n=194,478)
    145.57 ± 404.35
    104.41 ± 524.62
        Month 48 (n=185,421)
    163.30 ± 461.38
    76.90 ± 312.05
        Month 60 (n=60,116)
    202.47 ± 499.46
    93.61 ± 260.51
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48 and 60
    End point description
    The total lesion volume (T2 lesions) was measured by MRI scan. Analysis was performed on efficacy population. Here, ‘n’ = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: percent change
    arithmetic mean (standard deviation)
        Month 12 (n=226,558)
    21.44 ± 132.04
    9.09 ± 62.52
        Month 24 (n=224,542)
    17.53 ± 76.73
    13.89 ± 62.45
        Month 36 (n=216,529)
    24.24 ± 94.85
    22.02 ± 111.95
        Month 48 (n=204,462)
    21.98 ± 80.06
    19.46 ± 70.72
        Month 60 (n=67,128)
    32.03 ± 136.68
    17.95 ± 75.47
    No statistical analyses for this end point

    Secondary: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48 and 60
    End point description
    The brain parenchymal fraction was measured by MRI scan. Analysis was performed on efficacy population. Here, 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: percent change
    arithmetic mean (standard deviation)
        Month 12 (n=221,549)
    -1.65 ± 1.59
    -1.49 ± 1.55
        Month 24 (n=220,534)
    -1.77 ± 1.56
    -1.68 ± 1.64
        Month 36 (n=215,524)
    -1.92 ± 1.56
    -1.84 ± 1.71
        Month 48 (n=203,459)
    -2.02 ± 1.58
    -2.07 ± 1.78
        Month 60 (n=66,129)
    -2.11 ± 1.67
    -2.37 ± 1.65
    No statistical analyses for this end point

    Secondary: Change From Baseline in Self-reported Quality of Life (QoL) as Assessed by the Medical Outcome Study (MOS) 36- Item Short-Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Month 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Change From Baseline in Self-reported Quality of Life (QoL) as Assessed by the Medical Outcome Study (MOS) 36- Item Short-Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Month 12, 24, 36, 48 and 60
    End point description
    The MOS SF-36 is an extensively validated and widely used measure of QoL that assesses subjects’ perceptions of health status and its impact on their lives. It consisted of 36 items organised into 8 scales (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health). Two summary measures of physical and mental health, the PCS and MCS, respectively, were derived from scale aggregates, and were reported in this endpoint. The score range for each of these 2 summary scores was from 0 (worst) to 100 (best), higher scores indicated better QoL. Analysis was performed on efficacy population. Here, 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: score on a scale
    arithmetic mean (standard deviation)
        PCS: Month 12 (n=228,559)
    0.54 ± 9.38
    0.88 ± 8.72
        PCS: Month 24 (n=216,545)
    0.20 ± 9.25
    0.59 ± 9.10
        PCS: Month 36 (n=212,534)
    0.08 ± 9.88
    1.12 ± 9.18
        PCS: Month 48 (n=199,466)
    -0.52 ± 10.15
    0.68 ± 9.57
        PCS: Month 60 (n=80,176)
    -0.23 ± 8.85
    1.28 ± 8.88
        MCS: Month 12 (n=228,559)
    2.21 ± 12.29
    0.89 ± 11.24
        MCS: Month 24 (n=216,545)
    1.21 ± 12.23
    1.11 ± 11.93
        MCS: Month 36 (n=212,534)
    1.55 ± 12.23
    0.94 ± 11.88
        MCS: Month 48 (n=199,466)
    1.14 ± 12.93
    0.35 ± 12.38
        MCS: Month 60 (n=80,176)
    0.94 ± 14.01
    0.45 ± 11.39
    No statistical analyses for this end point

    Secondary: Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48 and 60
    End point description
    The FAMS is a self-reported multidimensional index comprising a total of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Each item (except those for “additional concerns”) was rated on a 5-point scale of 0 (lower quality of life) to 4 (higher quality of life). Total FAMS score was the sum of 44 scored items, which ranged from 0 (poor) to 176 (best), with higher numbers reflecting a higher quality of life. Analysis was performed on efficacy population. Here, 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: score on a scale
    arithmetic mean (standard deviation)
        Month 12 (n=230,573)
    1.05 ± 29.68
    2.83 ± 27.07
        Month 24 (n=222,551)
    -0.45 ± 30.30
    2.73 ± 28.62
        Month 36 (n=214,532)
    0.82 ± 30.52
    2.70 ± 28.94
        Month 48 (n=202,472)
    -3.73 ± 31.46
    1.16 ± 29.38
        Month 60 (n=81,181)
    -0.36 ± 31.25
    2.74 ± 26.61
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48 and 60
    End point description
    The EQ-5D is a generic, standardised instrument that provides a simple, descriptive profile and a single index value for health status used in the clinical and economic evaluation of health care as well as in population health surveys. The EQ-5D comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: some, moderate, and extreme problems. The 5 dimensional 3-level systems was converted into single index utility score ranges from 0 to 100, where 100=best health state; and 0=worst health state; higher scores indicated better outcome. Analysis was performed on efficacy population. Here, 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: score on a scale
    arithmetic mean (standard deviation)
        Month 12 (n=231,571)
    -0.01 ± 0.26
    -0.01 ± 0.26
        Month 24 (n=225,550)
    -0.02 ± 0.28
    -0.01 ± 0.26
        Month 36 (n=218,530)
    -0.04 ± 0.27
    -0.00 ± 0.26
        Month 48 (n=207,469)
    -0.03 ± 0.27
    -0.03 ± 0.27
        Month 60 (n=83,184)
    -0.03 ± 0.29
    -0.03 ± 0.25
    No statistical analyses for this end point

    Secondary: Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48 and 60

    Close Top of page
    End point title
    Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48 and 60
    End point description
    EQ-5D VAS was used to record a subject’s rating for his/her current health-related quality of life state and captured on a vertical VAS (0 to 100), where 0=worst imaginable health state to 100=best imaginable health state, and higher score indicated better outcome. Analysis was performed on efficacy population. Here, 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done only on the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    241
    598
    Units: score on a scale
    arithmetic mean (standard deviation)
        Month 12 (n=232,560)
    -2.09 ± 25.11
    -1.05 ± 24.57
        Month 24 (n=225,545)
    -1.57 ± 26.69
    -0.39 ± 21.44
        Month 36 (n=217,527)
    0.10 ± 22.61
    1.42 ± 20.64
        Month 48 (n=199,466)
    -1.08 ± 23.66
    -0.85 ± 23.94
        Month 60 (n=82,177)
    -3.26 ± 27.04
    -0.77 ± 26.26
    No statistical analyses for this end point

    Secondary: Modified Healthcare Resource Utilisation Questionnaire (HRUQ): Number of Subjects Who Reported Change in Employment Situation, Availing of Sick Leaves, Admissions and Stays in Hospital, Rehabilitation Centers or Nursing Homes Due to Multiple Sclerosis

    Close Top of page
    End point title
    Modified Healthcare Resource Utilisation Questionnaire (HRUQ): Number of Subjects Who Reported Change in Employment Situation, Availing of Sick Leaves, Admissions and Stays in Hospital, Rehabilitation Centers or Nursing Homes Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire(HRUQ) designed to evaluate economic impact of MS. Questionnaire addresses following areas: employment situation & changes in employment situation;sick leave,admissions & stays in hospital, rehabilitation centers (RC)/nursing homes(NH); typical MS-related investments and devices (eg., walking aids, wheelchairs); assistance by community or social services (e.g., home nurse, transportation), or help from family/friends. Each question requires binary answer (yes/no). Subjects who reported "Yes" as an answer to the specified questions were reported. Efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for endpoint and 'n' = subjects with available data. Data collection and analysis for this endpoint was done on overall population along with 2 planned subgroups(DAT and IAT). "M"="months"
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1020
    231
    573
    Units: subjects
        Employment situation change:M0(n=381,84,224)
    12
    3
    7
        Employment situation change:M12(n=1014,230,573)
    44
    11
    25
        Employment situation change:M24(n=960,220,537)
    40
    14
    19
        Employment situation change:M36(n=929,217,518)
    44
    12
    26
        Employment situation change:M48(n=850,200,467)
    38
    4
    24
        Employment situation change:M60(n=367,81,182)
    14
    3
    8
        Had sick leave:M0(n= n=265,57,157)
    21
    6
    14
        Had sick leave:M12(n=642,127,373)
    77
    19
    45
        Had sick leave:M24(n=645,148,360)
    80
    23
    42
        Had sick leave:M36(n=584,145,324)
    78
    21
    44
        Had sick leave:M48(n=565,134,307)
    60
    18
    31
        Had sick leave:M60(n=266,56,127)
    25
    9
    10
        Had hospital admission:M0(n= n=337,73,203)
    32
    4
    23
        Had hospital admission:M12(n=1018,231,570)
    109
    28
    59
        Had hospital admission:M24(n=974,223,544)
    95
    26
    53
        Had hospital admission:M36(n=938,218,522)
    106
    27
    58
        Had hospital admission:M48(n=859,202,471)
    89
    20
    51
        Had hospital admission:M60(n=374,81,184)
    28
    12
    11
        Had spent time in RC:M0(n= n=334,74,200)
    8
    0
    6
        Had spent time in RC:M12(n=1020,230,573)
    45
    12
    21
        Had spent time in RC :M24(n=968,223,540)
    45
    17
    18
        Had spent time in RC:M36(n=946,217,532)
    36
    12
    19
        Had spent time in RC:M48(n=864,203,474)
    45
    12
    24
        Had spent time in RC:M60(n=374,81,184)
    18
    5
    6
        Had spent time in NH:M0(n= n=332,73,198)
    0
    0
    0
        Had spent time in NH:M12(n=1019,229,572)
    8
    0
    5
        Had spent time in NH :M24(n=972,222,545)
    7
    3
    4
        Had spent time in NH:M36(n=938,218,523)
    8
    3
    3
        Had spent time in NH:M48(n=860,202,472)
    11
    4
    4
        Had spent time in NH:M60(n=369,81,184)
    6
    0
    4
    No statistical analyses for this end point

    Secondary: Modified HRUQ: Number of Subjects Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis

    Close Top of page
    End point title
    Modified HRUQ: Number of Subjects Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate economic impact of MS. Questionnaire addresses following areas: employment situation and changes in employment situation;admissions & stays in hospital, rehabilitation centers/nursing homes; typical MS-related investments and devices (eg,walking aids, wheelchairs); assistance by community or social services (e.g.,home nurse, transportation), or help from family/friends. Each question requires a binary answer (yes/no). Subjects who reported "Yes" as an answer to the specified questions were reported. Efficacy population. ‘Number of subjects analysed’ = subjects evaluable for endpoint and 'n' = subjects with available data. Data collection and analysis for this endpoint was done on overall population along with 2 planned subgroups (DAT and IAT). "M" denotes "Month".
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1020
    231
    573
    Units: subjects
        Change to house, apartment,car:M 0(n=339,75,202)
    7
    0
    3
        Change to house, apartment,car:M12(n=1020,231,571)
    42
    11
    21
        Change to house,apartment,car:M 24(n=972,222,544)
    47
    10
    25
        Change to house,apartment,car:M 36(n=944,219,527)
    45
    16
    15
        Change to house,apartment,car:M 48(n=859,203,472)
    42
    10
    25
        Change to house,apartment,car:M 60(n=372,80,185)
    12
    5
    3
        Had required assistance:M 0(n=335,72,201)
    24
    4
    10
        Had required assistance:M 12(n=1015,227,573)
    88
    24
    45
        Had required assistance:M 24(n=962,221,535)
    86
    26
    44
        Had required assistance:M 36(n=937,217,522)
    79
    22
    35
        Had required assistance:M 48(n=852,203,466)
    75
    12
    45
        Had required assistance:M 60(n=369,82,180)
    26
    8
    10
        Had required other assistance:M 0(n=335,71,202)
    77
    15
    48
        Had required other assistance:M 12(n=1011,226,572)
    252
    57
    144
        Had required other assistance:M 24(n=958,222,530)
    241
    57
    135
        Had required other assistance:M 36(n=936,217,523)
    215
    48
    119
        Had required other assistance:M 48(n=848,201,463)
    211
    49
    119
        Had required other assistance:M 60(n=367,82,180)
    66
    22
    27
    No statistical analyses for this end point

    Secondary: Health Related Productivity Questionnaire (HRPQ): Number of Subjects Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis

    Close Top of page
    End point title
    Health Related Productivity Questionnaire (HRPQ): Number of Subjects Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Current employment status of subjects (i.e. Part Time/Full Time/Not Employed) was reported in this endpoint. Analysis was performed on efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1025
    234
    575
    Units: subjects
        Full time: Month 0 (n=1025,234,575)
    528
    127
    297
        Part time: Month 0 (n=1025,234,575)
    98
    20
    54
        Not employed: Month 0 (n=1025,234,575)
    399
    87
    224
        Full time: Month 12 (n=1013,229,569)
    511
    121
    291
        Part time: Month 12 (n=1013,229,569)
    104
    20
    53
        Not employed: Month 12 (n=1013,229,569)
    398
    88
    225
        Full time: Month 24 (n=980,223,549)
    488
    118
    273
        Part time: Month 24 (n=980,223,549)
    117
    21
    66
        Not employed: Month 24 (n=980,223,549)
    375
    84
    210
        Full time: Month 36 (n=943,216,530)
    478
    109
    273
        Part time: Month 36 (n=943,216,530)
    108
    23
    57
        Not employed: Month 36 (n=943,216,530)
    357
    84
    200
        Full time: Month 48 (n=860,204,469)
    424
    108
    225
        Part time: Month 48 (n=860,204,469)
    103
    21
    57
        Not employed: Month 48 (n=860,204,469)
    333
    75
    187
        Full time: Month 60 (n=374,82,183)
    189
    37
    97
        Part time: Month 60 (n=374,82,183)
    43
    10
    18
        Not employed: Month 60 (n=374,82,183)
    142
    35
    68
    No statistical analyses for this end point

    Secondary: HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Data for “total scheduled working hours of subjects; number of hours missed from work by subjects due to MS” were reported in this endpoint. Analysis was performed on efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    675
    153
    380
    Units: hours
    arithmetic mean (standard deviation)
        Total scheduled working hour:Month0(n=660,153,374)
    32.9 ± 16.1
    34.0 ± 14.6
    32.2 ± 16.1
        Total scheduled workinghour:Month12(n=675,152,380)
    32.5 ± 16.6
    33.6 ± 15.4
    32.3 ± 16.6
        Total scheduled workinghour:Month24(n=647,149,367)
    31.6 ± 16.1
    33.2 ± 15.5
    30.8 ± 16.1
        Total scheduled workinghour:Month36(n=615,137,343)
    33.3 ± 15.3
    33.6 ± 16.4
    33.1 ± 15.1
        Total scheduled workinghour:Month48(n=559,137,302)
    32.9 ± 17.0
    34.4 ± 19.7
    31.3 ± 16.3
        Total scheduled workinghour:Month60(n=249,52,124)
    31.1 ± 16.6
    27.3 ± 18.9
    31.1 ± 15.8
        Number of hours missed from work:Month0(n=39,8,21)
    11.7 ± 12.8
    9.8 ± 12.1
    15.2 ± 15.0
        Number of hour missed fromwork:Month12(n=47,14,23)
    9.0 ± 10.2
    6.7 ± 3.6
    10.1 ± 12.2
        Number of hour missed fromwork:Month24(n=41,9,22)
    10.4 ± 10.9
    6.7 ± 6.1
    10.6 ± 11.3
        Number of hour missed fromwork:Month36(n=35,6,21)
    18.7 ± 50.8
    9.3 ± 5.9
    24.7 ± 65.4
        Number of hour missed fromwork:Month48(n=42,11,21)
    28.0 ± 77.1
    21.5 ± 23.1
    37.7 ± 107.6
        umber of hour missed fromwork:Month60(n=12,2,5)
    13.9 ± 13.0
    14.5 ± 13.4
    13.4 ± 13.4
    No statistical analyses for this end point

    Secondary: HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output due to MS were reported in this endpoint. Analysis was performed on efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    622
    145
    351
    Units: percentage impact on work output
    arithmetic mean (standard deviation)
        Month 0 (n=622,145,349)
    8.5 ± 19.5
    6.2 ± 14.4
    10.2 ± 22.3
        Month 12 (n=622,138,351)
    9.0 ± 20.2
    8.7 ± 18.0
    9.5 ± 21.5
        Month 24 (n=596,137,335)
    9.8 ± 21.3
    9.9 ± 20.4
    9.4 ± 21.2
        Month 36 (n=571,128,316)
    9.4 ± 19.9
    9.2 ± 20.0
    9.9 ± 21.3
        Month 48 (n=525,129,279)
    9.7 ± 22.0
    12.2 ± 25.4
    9.3 ± 21.7
        Month 60 (n=231,43,115)
    9.2 ± 19.9
    11.7 ± 22.3
    8.1 ± 18.9
    No statistical analyses for this end point

    Secondary: HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. Questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores (HC) due to MS. Data for "total scheduled household chores hours; number of hours missed from planned household chores by subjects due to MS" were reported in this endpoint. Analysis was performed on efficacy population. Here, ‘ number of subjects analysed’=subjects evaluable for this endpoint and 'n'=subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    1004
    228
    562
    Units: hours
    arithmetic mean (standard deviation)
        Total scheduled HC hours:Month 0(n=993,228,558)
    10.8 ± 10.6
    9.8 ± 8.3
    11.0 ± 11.0
        Total scheduled HC hours:Month 12(n=1004,226,562)
    10.9 ± 11.5
    10.3 ± 10.1
    11.1 ± 11.7
        Total scheduled HC hours:Month 24(n=954,219,538)
    10.6 ± 11.4
    10.2 ± 11.6
    10.9 ± 11.4
        Total scheduled HC hours:Month 36(n=899,203,505)
    11.0 ± 12.1
    9.7 ± 10.2
    11.7 ± 13.1
        Total scheduled HC hours:Month 48(n=825,193,452)
    10.3 ± 10.3
    9.9 ± 8.9
    10.5 ± 10.6
        Total scheduled HC hours:Month 60(n=363,77,178)
    11.5 ± 12.6
    10.4 ± 8.7
    11.2 ± 11.1
        Number of hour missed from HC:Month0(n=188,39,104)
    6.0 ± 5.9
    4.7 ± 3.3
    6.5 ± 6.9
        Number of hour missed from HC:Month12(n=173,47,90)
    6.2 ± 6.6
    4.9 ± 3.5
    6.8 ± 7.7
        Number of hour missed fromHC:Month24(n=181,35,104)
    6.6 ± 9.3
    7.8 ± 9.0
    7.1 ± 10.6
        Number of hour missed from HC:Month36(n=161,33,91)
    7.0 ± 11.7
    6.1 ± 7.4
    7.7 ± 14.2
        Number of hour missed from HC:Month48(n=143,37,74)
    5.7 ± 8.4
    4.8 ± 4.3
    6.2 ± 10.6
        Number of hour missed from HC:Month60(n=51,15,24)
    5.9 ± 5.1
    5.3 ± 5.2
    5.8 ± 5.1
    No statistical analyses for this end point

    Secondary: HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output for household chores due to MS were reported in this endpoint. Analysis was performed on efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was planned to be done on the overall population along with the 2 planned subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    947
    212
    531
    Units: percentage impact on work output
    arithmetic mean (standard deviation)
        Month 0 (n=947,212,531)
    16.8 ± 25.8
    16.0 ± 23.8
    16.4 ± 26.0
        Month 12 (n=931,208,524)
    17.7 ± 27.5
    18.3 ± 27.3
    16.6 ± 26.6
        Month 24 (n=886,197,501)
    19.4 ± 28.1
    20.3 ± 28.5
    18.5 ± 27.4
        Month 36 (n=813,183,453)
    17.6 ± 26.6
    17.5 ± 25.9
    16.5 ± 26.2
        Month 48 (n=769,180,415)
    18.6 ± 27.7
    19.8 ± 28.8
    17.0 ± 26.8
        Month 60 (n=344,75,170)
    14.8 ± 25.0
    18.8 ± 28.3
    13.1 ± 22.9
    No statistical analyses for this end point

    Secondary: HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Mean and standard deviation data for duration of MS disease (in months) since the start of MS development in subjects was reported in this endpoint. Analysis was performed on efficacy population. Here, ‘number of subjects analysed’ = subjects evaluable for this endpoint. As pre-specified, data collection and analysis for this endpoint was done on the overall population along with the 2 subgroups (DAT and IAT).
    End point type
    Secondary
    End point timeframe
    Baseline up to end of the study (up to a maximum duration of 5.6 years)
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    997
    228
    559
    Units: months
        arithmetic mean (standard deviation)
    10.5 ± 4.5
    10.3 ± 4.0
    10.2 ± 5.0
    No statistical analyses for this end point

    Secondary: HRPQ: Number of Subjects Who Reported Impact on Work Due to Multiple Sclerosis

    Close Top of page
    End point title
    HRPQ: Number of Subjects Who Reported Impact on Work Due to Multiple Sclerosis
    End point description
    Subjects use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. Questionnaire addresses following content area: subject reported data regarding employment status, work productivity, impact on household chores due to MS. Number of subjects who reported "Yes" an answer to "forced me to work part-time when I wanted to work full-time; kept me from having a job when I wanted to work full-time; kept me from having a job when I wanted to work part-time; none of the above" questions were reported in this endpoint. Analysis was performed on efficacy population. ‘Number of subjects analysed’ = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category. As pre-specified, data collection and analysis for this endpoint was done on overall population along with the 2 subgroups(DAT&IAT).
    End point type
    Secondary
    End point timeframe
    Baseline up to end of the study (up to a maximum duration of 5.6 years)
    End point values
    Alemtuzumab Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT)
    Number of subjects analysed
    709
    164
    399
    Units: subjects
        Work part-time,want to work full time(n=125,22,81)
    125
    22
    81
        Kept from job,want to work full-time(n=168,32,88)
    168
    32
    88
        Kept from job,want to work part-time(n=81,20,42)
    81
    20
    42
        None of the above (n=709,164,399)
    709
    164
    399
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All AEs were collected from the Baseline until the end of the study (up to a maximum duration of 5.6 years).
    Adverse event reporting additional description
    Reported AEs and death were TEAEs that is AEs that developed/worsened during the ‘treatment period’ (time from Baseline until the end of the study). Analysis was performed on safety population. As prespecified, safety analysis was done on the overall population along with 2 subgroups (DAT and IAT).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Delayed Alemtuzumab Treatment (DAT)
    Reporting group description
    Subjects from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Subjects received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Reporting group title
    Initial Alemtuzumab Treatment (IAT)
    Reporting group description
    Subjects from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Subjects received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Reporting group title
    Alemtuzumab
    Reporting group description
    All Subjects who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Subjects received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators’ discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

    Serious adverse events
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT) Alemtuzumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    55 / 241 (22.82%)
    133 / 598 (22.24%)
    237 / 1062 (22.32%)
         number of deaths (all causes)
    0
    10
    11
         number of deaths resulting from adverse events
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flushing
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Artery Thrombosis
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal Cell Carcinoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast Cancer
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brenner Tumour
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervix Carcinoma Stage 0
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cutaneous T-Cell Lymphoma
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder Cancer Stage Iii
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal Proliferative Breast Lesion
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive Ductal Breast Carcinoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive Lobular Breast Carcinoma
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal Squamous Cell Carcinoma
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Squamous Cell Carcinoma Stage Iii
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant Melanoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant Melanoma In Situ
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant Neoplasm Of Unknown Primary Site
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Neuroma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-Hodgkin's Lymphoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian Adenoma
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cancer
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian Germ Cell Teratoma
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate Cancer
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal Cancer Metastatic
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Squamous Cell Carcinoma Of Skin
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine Cancer
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine Leiomyoma
         subjects affected / exposed
    1 / 241 (0.41%)
    3 / 598 (0.50%)
    5 / 1062 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune Reconstitution Inflammatory Syndrome
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Missed
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abortion Spontaneous
         subjects affected / exposed
    3 / 241 (1.24%)
    6 / 598 (1.00%)
    11 / 1062 (1.04%)
         occurrences causally related to treatment / all
    0 / 5
    2 / 7
    2 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anembryonic Gestation
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ectopic Pregnancy
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foetal Distress Syndrome
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hellp Syndrome
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Missed Labour
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pre-Eclampsia
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy
         subjects affected / exposed
    2 / 241 (0.83%)
    4 / 598 (0.67%)
    7 / 1062 (0.66%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prolonged Labour
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Catheter Site Pain
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complication Associated With Device
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Drug Intolerance
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Psychiatric disorders
    Alcoholism
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Behaviour Disorder
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Completed Suicide
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Confusional State
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 241 (0.83%)
    2 / 598 (0.33%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression Suicidal
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug Abuse
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Major Depression
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental Disorder
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Substance-Induced Psychotic Disorder
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal Ideation
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide Attempt
         subjects affected / exposed
    2 / 241 (0.83%)
    2 / 598 (0.33%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical Dysplasia
         subjects affected / exposed
    1 / 241 (0.41%)
    3 / 598 (0.50%)
    5 / 1062 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometriosis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Female Genital Tract Fistula
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine Polyp
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal Haemorrhage
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain Contusion
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Burns Third Degree
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Face Injury
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur Fracture
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Induced Abortion Failed
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intentional Overdose
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus Injury
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Hypotension
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull Fractured Base
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural Haematoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon Rupture
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna Fracture
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Limb Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist Fracture
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Antiphospholipid Antibodies Positive
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Human Papilloma Virus Test Positive
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphocyte Count Decreased
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Left Ventricular Failure
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute Myocardial Infarction
         subjects affected / exposed
    1 / 241 (0.41%)
    2 / 598 (0.33%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular Block
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bundle Branch Block Left
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left Ventricular Dysfunction
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral Valve Incompetence
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial Effusion
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus Tachycardia
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular Arrhythmia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial Septal Defect
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital Cystic Kidney Disease
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital Nail Disorder
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foetal Chromosome Abnormality
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trisomy 21
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal Septum Deviation
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising Pneumonia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pneumomediastinum
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 241 (0.00%)
    3 / 598 (0.50%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Fibrosis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile Neutropenia
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune Thrombocytopenia
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 241 (0.41%)
    2 / 598 (0.33%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised Tonic-Clonic Seizure
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 241 (0.83%)
    1 / 598 (0.17%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limbic Encephalitis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss Of Consciousness
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbosacral Radiculopathy
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple Sclerosis
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple Sclerosis Relapse
         subjects affected / exposed
    6 / 241 (2.49%)
    18 / 598 (3.01%)
    30 / 1062 (2.82%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 30
    0 / 43
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Optic Neuritis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Partial Seizures
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post Herpetic Neuralgia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postural Tremor
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Resting Tremor
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxic Encephalopathy
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trigeminal Neuralgia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uhthoff's Phenomenon
         subjects affected / exposed
    3 / 241 (1.24%)
    5 / 598 (0.84%)
    9 / 1062 (0.85%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine Ophthalmopathy
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Exophthalmos
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eyelid Ptosis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Optic Ischaemic Neuropathy
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periorbital Oedema
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Haematotympanum
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis Ulcerative
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric Ulcer Perforation
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Ischaemia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive Pancreatitis
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis Acute
         subjects affected / exposed
    2 / 241 (0.83%)
    0 / 598 (0.00%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis Chronic
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    2 / 241 (0.83%)
    0 / 598 (0.00%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 241 (0.41%)
    2 / 598 (0.33%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis Haemorrhagic
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lupus Nephritis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    2 / 241 (0.83%)
    2 / 598 (0.33%)
    5 / 1062 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal Colic
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal Injury
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decubitus Ulcer
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin Ulcer
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back Pain
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint Contracture
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular Weakness
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic Lupus Erythematosus
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune Hypothyroidism
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune Thyroid Disorder
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune Thyroiditis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basedow's Disease
         subjects affected / exposed
    2 / 241 (0.83%)
    4 / 598 (0.67%)
    7 / 1062 (0.66%)
         occurrences causally related to treatment / all
    2 / 2
    4 / 4
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thyroid Dermatopathy
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes Mellitus
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic Ketosis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrolyte Imbalance
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 1 Diabetes Mellitus
         subjects affected / exposed
    0 / 241 (0.00%)
    3 / 598 (0.50%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 Diabetes Mellitus
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Abscess
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess Rupture
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal Abscess
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial Sepsis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 241 (0.00%)
    3 / 598 (0.50%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis Staphylococcal
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficile Infection
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia Urinary Tract Infection
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Bacterial Infection
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes Zoster
         subjects affected / exposed
    0 / 241 (0.00%)
    3 / 598 (0.50%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes Zoster Infection Neurological
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected Bite
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected Lymphocele
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella Infection
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised Infection
         subjects affected / exposed
    0 / 241 (0.00%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neonatal Pneumonia
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis Acute
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 241 (0.41%)
    4 / 598 (0.67%)
    9 / 1062 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Streptococcal
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative Wound Infection
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 598 (0.33%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 598 (0.17%)
    3 / 1062 (0.28%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scrotal Abscess
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 241 (0.41%)
    2 / 598 (0.33%)
    5 / 1062 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    0 / 241 (0.00%)
    3 / 598 (0.50%)
    4 / 1062 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    Urinary Tract Infection
         subjects affected / exposed
    2 / 241 (0.83%)
    4 / 598 (0.67%)
    9 / 1062 (0.85%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 4
    2 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection Bacterial
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 598 (0.17%)
    2 / 1062 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine Infection
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 598 (0.00%)
    1 / 1062 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Delayed Alemtuzumab Treatment (DAT) Initial Alemtuzumab Treatment (IAT) Alemtuzumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    150 / 241 (62.24%)
    338 / 598 (56.52%)
    601 / 1062 (56.59%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    15 / 241 (6.22%)
    27 / 598 (4.52%)
    54 / 1062 (5.08%)
         occurrences all number
    20
    34
    74
    Nervous system disorders
    Headache
         subjects affected / exposed
    37 / 241 (15.35%)
    67 / 598 (11.20%)
    125 / 1062 (11.77%)
         occurrences all number
    52
    87
    164
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    14 / 241 (5.81%)
    39 / 598 (6.52%)
    63 / 1062 (5.93%)
         occurrences all number
    23
    46
    86
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    15 / 241 (6.22%)
    19 / 598 (3.18%)
    43 / 1062 (4.05%)
         occurrences all number
    17
    19
    45
    Psychiatric disorders
    Depression
         subjects affected / exposed
    13 / 241 (5.39%)
    25 / 598 (4.18%)
    43 / 1062 (4.05%)
         occurrences all number
    13
    26
    45
    Insomnia
         subjects affected / exposed
    16 / 241 (6.64%)
    29 / 598 (4.85%)
    57 / 1062 (5.37%)
         occurrences all number
    17
    32
    62
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    13 / 241 (5.39%)
    18 / 598 (3.01%)
    37 / 1062 (3.48%)
         occurrences all number
    13
    18
    37
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    13 / 241 (5.39%)
    26 / 598 (4.35%)
    51 / 1062 (4.80%)
         occurrences all number
    16
    34
    64
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    19 / 241 (7.88%)
    39 / 598 (6.52%)
    69 / 1062 (6.50%)
         occurrences all number
    27
    45
    86
    Back Pain
         subjects affected / exposed
    16 / 241 (6.64%)
    30 / 598 (5.02%)
    62 / 1062 (5.84%)
         occurrences all number
    16
    34
    68
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    14 / 241 (5.81%)
    44 / 598 (7.36%)
    67 / 1062 (6.31%)
         occurrences all number
    17
    54
    81
    Herpes Zoster
         subjects affected / exposed
    15 / 241 (6.22%)
    29 / 598 (4.85%)
    50 / 1062 (4.71%)
         occurrences all number
    16
    35
    57
    Influenza
         subjects affected / exposed
    13 / 241 (5.39%)
    25 / 598 (4.18%)
    48 / 1062 (4.52%)
         occurrences all number
    13
    28
    55
    Nasopharyngitis
         subjects affected / exposed
    34 / 241 (14.11%)
    73 / 598 (12.21%)
    129 / 1062 (12.15%)
         occurrences all number
    60
    112
    204
    Sinusitis
         subjects affected / exposed
    11 / 241 (4.56%)
    34 / 598 (5.69%)
    57 / 1062 (5.37%)
         occurrences all number
    11
    45
    71
    Upper Respiratory Tract Infection
         subjects affected / exposed
    27 / 241 (11.20%)
    50 / 598 (8.36%)
    96 / 1062 (9.04%)
         occurrences all number
    29
    73
    123
    Urinary Tract Infection
         subjects affected / exposed
    37 / 241 (15.35%)
    78 / 598 (13.04%)
    151 / 1062 (14.22%)
         occurrences all number
    56
    143
    271

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Feb 2018
    Following changes were made: To add an optional pharmacogenomics substudy for exploratory analysis of genetic variations predictive of autoimmune conditions; to harmonise the list of AESIs within sections; to clarify procedure for routine urinalysis and microscopy; to clarify timing of human papilloma virus screening in women; to clarify interim analysis objective; to update information regarding risk of Listeria infection according to new Lemtrada summary of product characteristics.
    24 Jul 2019
    Following changes were made: To provide information about new safety concerns that have been identified from post-marketing use with alemtuzumab. This includes reports of autoimmune hepatitis and hemophagocytic lymphohistiocytosis, as well as temporally associated serious cardiovascular reactions; to add measures to minimise the risks of subjects included in clinical trials.
    28 Jan 2020
    Following changes were made: To address safety update based on recent post marketing safety monitoring findings; to update contraindications for re-treatment with alemtuzumab; To update the list of AESIs within sections; to increase frequency of liver function tests from every 3 months to every month.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA