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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind Study of PF-05280586 Versus Rituximab for the First-Line Treatment of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma

    Summary
    EudraCT number
    2014-000132-41
    Trial protocol
    BE   GB   DE   ES   IT   PT   AT   HR   GR  
    Global end of trial date
    19 Apr 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    31 Mar 2019
    First version publication date
    18 Oct 2018
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    B3281006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02213263
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Study Name: REFLECTIONS
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.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
    25 Jun 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Oct 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Apr 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to compare the efficacy of PF-05280586 to rituximab-EU when administered as a first-line treatment to subjects with cluster of differentiation 20 (CD20)-positive, low tumor burden (LTB) follicular lymphoma (FL).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Sep 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 7
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Thailand: 4
    Country: Number of subjects enrolled
    Turkey: 16
    Country: Number of subjects enrolled
    Ukraine: 10
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    United States: 44
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Belarus: 3
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Brazil: 26
    Country: Number of subjects enrolled
    Croatia: 6
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Georgia: 3
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Greece: 8
    Country: Number of subjects enrolled
    India: 5
    Country: Number of subjects enrolled
    Italy: 63
    Country: Number of subjects enrolled
    Japan: 51
    Country: Number of subjects enrolled
    Korea, Republic of: 11
    Country: Number of subjects enrolled
    Lebanon: 3
    Country: Number of subjects enrolled
    Mexico: 6
    Country: Number of subjects enrolled
    Peru: 5
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Portugal: 13
    Country: Number of subjects enrolled
    Puerto Rico: 1
    Country: Number of subjects enrolled
    Romania: 6
    Country: Number of subjects enrolled
    Russian Federation: 19
    Worldwide total number of subjects
    394
    EEA total number of subjects
    176
    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)
    259
    From 65 to 84 years
    132
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 394 subjects were enrolled and randomized in 1:1 ratio to 1 of the 2 study treatment arms: PF-05280586 (Rituximab-Pfizer) and Rituximab-EU (MabThera®).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Rituximab-EU
    Arm description
    Subjects received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab-EU
    Investigational medicinal product code
    Other name
    MabThera
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Rituximab-EU IV infusion at a dose of 375 mg/m^2 on Days 1, 8, 15 and 22.

    Arm title
    PF-05280586
    Arm description
    Subjects received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-05280586
    Investigational medicinal product code
    Other name
    Rituximab-Pfizer
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Days 1, 8, 15 and 22.

    Number of subjects in period 1
    Rituximab-EU PF-05280586
    Started
    198
    196
    Treated
    197
    196
    Completed
    170
    170
    Not completed
    28
    26
         Progressive disease
    20
    14
         Protocol deviation
    -
    1
         Adverse events(AE) related to study drug
    -
    2
         AE not related to study drug
    1
    1
         Insufficient clinical response
    4
    3
         No longer willing to participate
    3
    4
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rituximab-EU
    Reporting group description
    Subjects received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Reporting group title
    PF-05280586
    Reporting group description
    Subjects received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Reporting group values
    Rituximab-EU PF-05280586 Total
    Number of subjects
    198 196 394
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    58.3 ± 12.8 58.7 ± 12.1 -
    Sex: Female, Male
    Units: Subjects
        Female
    106 110 216
        Male
    92 86 178
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    44 30 74
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    0 1 1
        White
    146 158 304
        More than one race
    0 0 0
        Unknown or Not Reported
    8 7 15
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    26 31 57
        Not Hispanic or Latino
    172 165 337
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Rituximab-EU
    Reporting group description
    Subjects received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Reporting group title
    PF-05280586
    Reporting group description
    Subjects received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Days 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Primary: Overall Response Rate (ORR): Percentage of Subjects With Overall Response (OR) at Week 26

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    End point title
    Overall Response Rate (ORR): Percentage of Subjects With Overall Response (OR) at Week 26
    End point description
    ORR was defined as the percentage of subjects who achieved complete response (CR) or partial response (PR) in accordance with the revised response criteria for malignant lymphoma (Cheson 2007). CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. Intent to treatment (ITT) population included all subjects who were randomized.
    End point type
    Primary
    End point timeframe
    Week 26
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    198
    196
    Units: percentage of subjects
        number (confidence interval 95%)
    70.7 (63.8 to 76.9)
    75.5 (68.9 to 81.4)
    Statistical analysis title
    PF-05280586 versus Rituximab-EU
    Statistical analysis description
    Difference in ORR between PF-05280586 and rituximab-EU was computed using the stratified Mantel-Haenszel method. The 95 percent (%) confidence interval (CI) for the difference was calculated using the asymptotic stratified method proposed by Miettinen and Nurminen.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    394
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [1]
    Method
    Parameter type
    Difference in ORR
    Point estimate
    4.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.16
         upper limit
    13.47
    Notes
    [1] - Equivalence was tested within the pre-specified margins of (-16%, 16%) 95% confidence interval.

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in subjects who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Safety population included all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: subjects
        AEs
    145
    156
        SAEs
    15
    17
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by investigator. AEs included both serious and non-serious AEs. Safety population included all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: subjects
        AEs
    94
    86
        SAEs
    2
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03

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    End point title
    Number of Subjects With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
    End point description
    An AE was any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 (Life threatening) events caused subject to be in imminent danger of death, Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Safety population included all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: subjects
    26
    28
    No statistical analyses for this end point

    Secondary: Number of Subjects With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03

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    End point title
    Number of Subjects With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
    End point description
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated; Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused subject to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Safety population included all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: subjects
    8
    9
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities

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    End point title
    Number of Subjects With Clinically Significant Laboratory Abnormalities
    End point description
    Criteria for clinically significant laboratory abnormalities included total bilirubin (TB) less than (<) 2*upper limit of normal (ULN), alanine aminotransferase (ALT)<3*ULN; TB<2*ULN, ALT more than (>) 3 equal to (=) *ULN; TB<2*ULN, aspartate aminotransferase (AST)<3*ULN; TB<2*ULN, AST>=3*ULN. Data for only those categories are reported for which at least one subject had clinically significant laboratory abnormality. Safety population included all subjects who received at least 1 dose of any study drug. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    195
    Units: subjects
        TB<2*ULN, ALT<3*ULN
    194
    192
        TB<2*ULN, ALT>=3*ULN
    3
    3
        TB<2*ULN, AST<3*ULN
    196
    195
        TB<2*ULN, AST>=3*ULN
    1
    0
    No statistical analyses for this end point

    Secondary: Time to Treatment Failure (TTF)

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    End point title
    Time to Treatment Failure (TTF)
    End point description
    TTF was defined as the time (in months) from date of randomization to first progression of disease based on central review, death due to any cause, or permanent discontinuation from treatment, or discontinuation from study for any reason, whichever came first. Progression was defined as any new lesion or increase by greater than equal to (>=) 50 percent (%) of previously involved sites from nadir. TTF was calculated using Kaplan-Meier method. ITT population included all subjects who were randomized. Here, '99999' signifies that due to smaller number of subjects with an event, median and upper limit of 95% CI could not be calculated. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    48
    54
    Units: months
        median (confidence interval 95%)
    18.9 (12.6 to 18.9)
    99999 (12.3 to 99999)
    Statistical analysis title
    PF-05280586 versus Rituximab-EU
    Statistical analysis description
    Hazard ratio and its confidence intervals (CIs) were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.45 [2]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.163
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.786
         upper limit
    1.72
    Notes
    [2] - A log-rank test stratified by Follicular Lymphoma International Prognostic Index 2 (FLIPI2) risk was used to compare the treatment groups with respect to TTF at a 2-sided alpha level of 0.05.

    Secondary: Progression-Free Survival (PFS)

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    End point title
    Progression-Free Survival (PFS)
    End point description
    PFS was defined as the time (in months) from date of randomization to first progression of disease (PD ) based on central review or death due to any cause in the absence of documented PD. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method. ITT population included all subjects who were randomized. Here, '99999' signifies that due to smaller number of subjects with an event, median and 95% CI could not be calculated. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression or death due to any cause or up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    28
    37
    Units: months
        median (confidence interval 95%)
    18.9 (12.6 to 18.9)
    99999 (99999 to 99999)
    Statistical analysis title
    PF-05280586 versus Rituximab-EU
    Statistical analysis description
    Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.189 [3]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.393
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.847
         upper limit
    2.291
    Notes
    [3] - A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to PFS at a 2-sided alpha level of 0.05.

    Secondary: Percentage of Subjects With Complete Remission (CR) at Week 26

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    End point title
    Percentage of Subjects With Complete Remission (CR) at Week 26
    End point description
    Complete Remission (CR) was defined as disappearance of all evidence of disease. CR was assessed by central review based on scans done at Week 26. ITT population included all subjects who were randomized.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    198
    196
    Units: percentage of subjects
        number (confidence interval 95%)
    28.3 (22.1 to 35.1)
    26.0 (20.0 to 32.8)
    Statistical analysis title
    PF-05280586 versus Rituximab-EU
    Statistical analysis description
    Difference in CR between PF-05280586 and rituximab-EU was computed using the stratified Mantel-Haenszel method. The 95% confidence interval for the difference was calculated using the asymptotic stratified method proposed by Miettinen and Nurminen.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    394
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.09
         upper limit
    6.5

    Secondary: Duration of Response (DOR)

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    End point title
    Duration of Response (DOR)
    End point description
    DOR was defined as the time (in months) from date of the first documentation of overall response (CR or PR) to the first documentation of progressive disease (PD) based on central review or to death due to any cause in the absence of documented PD. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method. The response-evaluable population was defined as all randomized subjects who received at least 1 dose of study drug, had adequate disease assessment at baseline, and at least 1 post baseline response assessment. Here, '99999' signifies that due to small number of subjects with an event, median and upper limit of 95% CI could not be calculated. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From date of first documentation of overall response to first documentation of PD or to death due to any cause in absence of PD or up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    19
    28
    Units: months
        median (confidence interval 95%)
    15.4 (10.4 to 15.4)
    99999 (9.6 to 99999)
    Statistical analysis title
    PF-05280586 versus Rituximab-EU
    Statistical analysis description
    Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.185 [4]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.492
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.823
         upper limit
    2.704
    Notes
    [4] - A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to DOR at a 2-sided alpha level of 0.05.

    Secondary: Overall Survival

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    End point title
    Overall Survival
    End point description
    Overall survival was defined as the time (in months) from date of randomization to death due to any cause. For subjects who were alive, overall survival was censored at the last contact. Overall survival was calculated using Kaplan-Meier method. ITT population included all subjects who were randomized. Here, '99999' signifies that due to single subject with an event, median and 95% CI could not be calculated.
    End point type
    Secondary
    End point timeframe
    From randomization until death due to any cause or up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    198
    196
    Units: months
        median (confidence interval 95%)
    18.9 (-99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    PF-05280586 versus Rituximab EU
    Statistical analysis description
    Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
    Comparison groups
    Rituximab-EU v PF-05280586
    Number of subjects included in analysis
    394
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.319 [5]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    2.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    99999
    Notes
    [5] - A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to overall survival at a 2-sided alpha level of 0.05.

    Secondary: Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU

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    End point title
    Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU
    End point description
    The pharmacokinetic analysis set (PKAS) included subjects who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Predose (within 4 hours prior to start of infusion) on Days 1, 8, 15 and 22; within 15 minutes prior to end of infusion on Days 1 and 22
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    132
    138
    Units: nanograms per milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    334848.88 ± 33
    337708.05 ± 36
    No statistical analyses for this end point

    Secondary: Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU

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    End point title
    Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU
    End point description
    The pharmacokinetic analysis set (PKAS) included subjects who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Predose (within 4 hours prior to the start of dosing) on Days 1, 8, 15, and 22
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1 (n=195,192)
    0.01 ± 577
    0.01 ± 1320
        Day 8 (n=197,194)
    62311.74 ± 47
    66669.15 ± 45
        Day 15 (n=194,193)
    109619.73 ± 43
    119026.91 ± 29
        Day 22 (n=194,194)
    144650.79 ± 68
    158294.91 ± 32
    No statistical analyses for this end point

    Secondary: Cluster of Differentiation (CD) 19-Positive B-Cell Counts

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    End point title
    Cluster of Differentiation (CD) 19-Positive B-Cell Counts
    End point description
    The modified ITT (mITT) Population included all subjects who were randomized and received at least 1 dose of any study drug. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 3, 4, 5, 13, 26, 39 and 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: cells per microliter
    median (full range (min-max))
        Baseline (n= 174,175)
    114.2 (0.6 to 2313.1)
    119.9 (10.9 to 1310.1)
        Week 2 (n=168,159)
    1.0 (0.2 to 44.8)
    0.8 (0.2 to 136.0)
        Week 3 (n= 149,149)
    0.6 (0.2 to 19.5)
    0.6 (0.2 to 248.1)
        Week 4 (n=143,114)
    0.5 (0.2 to 8.7)
    0.4 (0.2 to 144.5)
        Week 5 (n=118,128)
    0.5 (0.2 to 19.0)
    0.4 (0.2 to 19.0)
        Week 13 (n=106,103)
    0.5 (0.2 to 130.7)
    0.5 (0.2 to 183.7)
        Week 26 (n=142,123)
    1.2 (0.2 to 496.5)
    0.9 (0.2 to 329.8)
        Week 39 (n=157,135)
    21.7 (0.3 to 341.0)
    10.7 (0.2 to 442.7)
        Week 52 (n=151,147)
    60.8 (1.4 to 413.0)
    51.6 (0.3 to 597.9)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)

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    End point title
    Number of Subjects With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
    End point description
    Human serum ADA samples were analysed for the presence or absence of anti-rituximab antibodies or anti-PF-05280586 antibodies using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Human NAb serum samples testing ADA positive were analysed for the presence or absence of neutralizing anti-rituximab antibody and neutralizing anti-PF-05280586 antibody using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Subjects with their ADA titer >= 1.88 were considered to be ADA positive. Only subjects with a positive ADA result were further tested for NAb. Safety population included all subjects who received at least 1 dose of any study drug. Here, 'Number of subjects analysed' signifies number of subjects evaluable for this endpoint. Here, ‘n’ signifies number of subjects evaluable for this endpoint for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    195
    Units: subjects
        ADA Positive (n = 197, 195)
    39
    43
        NAB Positive (n = 39, 43)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Immune-Based Adverse Effects

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    End point title
    Number of Subjects Reporting Immune-Based Adverse Effects
    End point description
    Immune-based adverse effects included infusion related reaction (IRR), adverse events which fulfill Sampson’s criteria, and adverse events which belong to the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) anaphylaxis or hypersensitivity reactions. The Safety analysis population include all subjects who received at least 1 dose of any study treatment. Potential allergic and anaphylactic reactions were identified programmatically based on the criteria of Sampson et al, (2006).
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    Rituximab-EU PF-05280586
    Number of subjects analysed
    197
    196
    Units: subjects
        IRR reported
    59
    49
        AE based on Sampson’s criteria
    17
    17
        Anaphylaxis/Hypersensitivity (SMQ)
    48
    39
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to end of study (up to 52 weeks)
    Adverse event reporting additional description
    Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Analysis was performed on safety population.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    PF-05280586
    Reporting group description
    Subjects received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Reporting group title
    Rituximab-EU
    Reporting group description
    Subjects received Rituximab-EU IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.

    Serious adverse events
    PF-05280586 Rituximab-EU
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 196 (8.67%)
    15 / 197 (7.61%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Serum sickness
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric artery stenosis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral sinusitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    PF-05280586 Rituximab-EU
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    153 / 196 (78.06%)
    143 / 197 (72.59%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Flushing
         subjects affected / exposed
    1 / 196 (0.51%)
    4 / 197 (2.03%)
         occurrences all number
    1
    4
    Hot flush
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Hypertension
         subjects affected / exposed
    5 / 196 (2.55%)
    7 / 197 (3.55%)
         occurrences all number
    9
    13
    Hypotension
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Lymphoedema
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Haematoma
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Infected neoplasm
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Lung adenocarcinoma stage I
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Non-Hodgkin’s lymphoma
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Meningioma
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Cytokine release syndrome
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Social circumstances
    Menopause
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    9 / 196 (4.59%)
    13 / 197 (6.60%)
         occurrences all number
    11
    15
    Axillary pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Catheter site pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Catheter site related reaction
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Chest discomfort
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Chest pain
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    2
    3
    Chills
         subjects affected / exposed
    3 / 196 (1.53%)
    3 / 197 (1.52%)
         occurrences all number
    4
    4
    Discomfort
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Face oedema
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Facial pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Fatigue
         subjects affected / exposed
    12 / 196 (6.12%)
    13 / 197 (6.60%)
         occurrences all number
    15
    16
    Feeling abnormal
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Feeling cold
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Feeling hot
         subjects affected / exposed
    2 / 196 (1.02%)
    2 / 197 (1.02%)
         occurrences all number
    3
    2
    Generalised oedema
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Influenza like illness
         subjects affected / exposed
    2 / 196 (1.02%)
    4 / 197 (2.03%)
         occurrences all number
    2
    4
    Infusion site bruising
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Infusion site erythema
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Infusion site extravasation
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Infusion site pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Malaise
         subjects affected / exposed
    3 / 196 (1.53%)
    0 / 197 (0.00%)
         occurrences all number
    6
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Oedema
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 196 (1.02%)
    7 / 197 (3.55%)
         occurrences all number
    2
    7
    Pain
         subjects affected / exposed
    3 / 196 (1.53%)
    3 / 197 (1.52%)
         occurrences all number
    3
    7
    Peripheral swelling
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    11 / 196 (5.61%)
    11 / 197 (5.58%)
         occurrences all number
    11
    12
    Suprapubic pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Swelling
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Affect lability
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Agitation
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Anxiety
         subjects affected / exposed
    6 / 196 (3.06%)
    7 / 197 (3.55%)
         occurrences all number
    6
    8
    Confusional state
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Depression
         subjects affected / exposed
    3 / 196 (1.53%)
    2 / 197 (1.02%)
         occurrences all number
    4
    2
    Gastrointestinal somatic symptom disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Irritability
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Insomnia
         subjects affected / exposed
    5 / 196 (2.55%)
    8 / 197 (4.06%)
         occurrences all number
    6
    18
    Panic attack
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Restlessness
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Breast pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Breast tenderness
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Menorrhagia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Genital burning sensation
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Metrorrhagia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Ovarian cyst
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pelvic pain
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    2
    Prostatitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Scrotal pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Testicular pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Vaginal haemorrhage
         subjects affected / exposed
    3 / 196 (1.53%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Vulvovaginal inflammation
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Bone contusion
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Chest injury
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Contusion
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Fall
         subjects affected / exposed
    5 / 196 (2.55%)
    2 / 197 (1.02%)
         occurrences all number
    5
    2
    Hand fracture
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Head injury
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Humerus fracture
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Infusion related reaction
         subjects affected / exposed
    49 / 196 (25.00%)
    58 / 197 (29.44%)
         occurrences all number
    58
    63
    Laceration
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Limb injury
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Neck injury
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Road traffic accident
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Skin abrasion
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Suture related complication
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Suture rupture
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tendon rupture
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Thermal burn
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Upper limb fracture
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Wound complication
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Wrist fracture
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Incision site pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 196 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 196 (1.53%)
    1 / 197 (0.51%)
         occurrences all number
    3
    1
    Blood potassium increased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Blood pressure decreased
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Blood pressure increased
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Blood urine present
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    2
    Neutrophil count decreased
         subjects affected / exposed
    5 / 196 (2.55%)
    0 / 197 (0.00%)
         occurrences all number
    5
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Serum ferritin decreased
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    4 / 196 (2.04%)
    1 / 197 (0.51%)
         occurrences all number
    4
    1
    Breath sounds abnormal
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Angina unstable
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Bradycardia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    5 / 196 (2.55%)
    2 / 197 (1.02%)
         occurrences all number
    6
    2
    Sinus bradycardia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    11 / 196 (5.61%)
    11 / 197 (5.58%)
         occurrences all number
    13
    11
    Dry throat
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Dysphonia
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Dyspnoea
         subjects affected / exposed
    6 / 196 (3.06%)
    8 / 197 (4.06%)
         occurrences all number
    6
    8
    Dyspnoea exertional
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Emphysema
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Hiccups
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hyperventilation
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Laryngeal discomfort
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Laryngeal inflammation
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Laryngeal oedema
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Laryngeal pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Lung disorder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Nasal discomfort
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Nasal pruritus
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Oropharyngeal discomfort
         subjects affected / exposed
    4 / 196 (2.04%)
    1 / 197 (0.51%)
         occurrences all number
    4
    1
    Paranasal sinus mucosal hypertrophy
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 196 (1.02%)
    10 / 197 (5.08%)
         occurrences all number
    2
    12
    Pharyngeal erythema
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Pharyngeal inflammation
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Pharyngeal oedema
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Pharyngeal paraesthesia
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Productive cough
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Pulmonary embolism
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Respiratory disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Rhinalgia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Suffocation feeling
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Throat tightness
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tonsillar disorder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tonsillar erythema
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Upper respiratory tract inflammation
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    4
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Sneezing
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Sinus disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Throat irritation
         subjects affected / exposed
    14 / 196 (7.14%)
    10 / 197 (5.08%)
         occurrences all number
    15
    10
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Lymph node pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Lymphopenia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Neutropenia
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Thrombocytopenia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 196 (1.02%)
    6 / 197 (3.05%)
         occurrences all number
    2
    8
    Burning sensation
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Dysgeusia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Head discomfort
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    16 / 196 (8.16%)
    19 / 197 (9.64%)
         occurrences all number
    18
    31
    Hypoaesthesia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Hypotonia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Intercostal neuralgia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Migraine
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Neuralgia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Nerve compression
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Paraesthesia
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    2
    3
    Polyneuropathy
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    5
    6
    Restless legs syndrome
         subjects affected / exposed
    3 / 196 (1.53%)
    1 / 197 (0.51%)
         occurrences all number
    3
    1
    Speech disorder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Syncope
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Tension headache
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Eye disorders
    Accommodation disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Cataract
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    2
    Conjunctival disorder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Diplopia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Erythema of eyelid
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Eye pruritus
         subjects affected / exposed
    0 / 196 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    3
    Lacrimation increased
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Meibomianitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Ocular hyperaemia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Entropion
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Visual impairment
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Ear disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Ear pain
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Ear pruritus
         subjects affected / exposed
    3 / 196 (1.53%)
    2 / 197 (1.02%)
         occurrences all number
    4
    2
    Hypoacusis
         subjects affected / exposed
    2 / 196 (1.02%)
    2 / 197 (1.02%)
         occurrences all number
    2
    2
    Tinnitus
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Vertigo
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    2
    3
    Vertigo positional
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Abdominal pain
         subjects affected / exposed
    7 / 196 (3.57%)
    3 / 197 (1.52%)
         occurrences all number
    12
    3
    Abdominal pain lower
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    9 / 196 (4.59%)
    5 / 197 (2.54%)
         occurrences all number
    9
    7
    Cheilitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Chronic gastritis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Colitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    8 / 196 (4.08%)
    8 / 197 (4.06%)
         occurrences all number
    9
    9
    Dental caries
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    14 / 196 (7.14%)
    12 / 197 (6.09%)
         occurrences all number
    16
    15
    Diverticulum intestinal
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dry mouth
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    5 / 196 (2.55%)
    2 / 197 (1.02%)
         occurrences all number
    6
    2
    Dysphagia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Enterocolitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Faeces soft
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gastritis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorder
         subjects affected / exposed
    3 / 196 (1.53%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Gingival pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gingival swelling
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Haematochezia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Inguinal hernia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Lip oedema
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Mouth swelling
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    15 / 196 (7.65%)
    17 / 197 (8.63%)
         occurrences all number
    19
    22
    Odynophagia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    2
    Oral discomfort
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Oral mucosal erythema
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Periodontal disease
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Salivary gland pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 196 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    6
    Swollen tongue
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Tooth disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    2 / 196 (1.02%)
    2 / 197 (1.02%)
         occurrences all number
    3
    2
    Vomiting
         subjects affected / exposed
    3 / 196 (1.53%)
    7 / 197 (3.55%)
         occurrences all number
    4
    7
    Renal and urinary disorders
    Bladder spasm
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Calculus bladder
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dysuria
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Nocturia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Pollakiuria
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Renal pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Strangury
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Urinary tract pain
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hepatocellular injury
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Angioedema
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Asteatosis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Blister
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dermatitis contact
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Drug eruption
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Erythema
         subjects affected / exposed
    7 / 196 (3.57%)
    2 / 197 (1.02%)
         occurrences all number
    7
    2
    Hyperhidrosis
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    4
    4
    Hyperkeratosis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Intertrigo
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Nail disorder
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Neurodermatitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Night sweats
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pruritus allergic
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    10 / 196 (5.10%)
    8 / 197 (4.06%)
         occurrences all number
    14
    9
    Rash erythematous
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Rash pruritic
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Scab
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Skin burning sensation
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Skin lesion
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Swelling face
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    3 / 196 (1.53%)
    6 / 197 (3.05%)
         occurrences all number
    3
    6
    Pruritus
         subjects affected / exposed
    13 / 196 (6.63%)
    22 / 197 (11.17%)
         occurrences all number
    14
    23
    Pruritus generalised
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Scar pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 196 (3.57%)
    6 / 197 (3.05%)
         occurrences all number
    8
    8
    Bone loss
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Back pain
         subjects affected / exposed
    8 / 196 (4.08%)
    10 / 197 (5.08%)
         occurrences all number
    8
    11
    Bone pain
         subjects affected / exposed
    0 / 196 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    3
    Costochondritis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Groin pain
         subjects affected / exposed
    3 / 196 (1.53%)
    2 / 197 (1.02%)
         occurrences all number
    3
    3
    Flank pain
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    3
    Haemarthrosis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Joint effusion
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Joint stiffness
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Joint swelling
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Muscle contracture
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Muscle twitching
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Musculoskeletal discomfort
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 196 (0.51%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    2 / 196 (1.02%)
    2 / 197 (1.02%)
         occurrences all number
    2
    2
    Myalgia
         subjects affected / exposed
    9 / 196 (4.59%)
    5 / 197 (2.54%)
         occurrences all number
    10
    5
    Neck pain
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    2
    3
    Osteoarthritis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Pain in extremity
         subjects affected / exposed
    7 / 196 (3.57%)
    4 / 197 (2.03%)
         occurrences all number
    9
    4
    Posture abnormal
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pubic pain
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Spinal pain
         subjects affected / exposed
    2 / 196 (1.02%)
    2 / 197 (1.02%)
         occurrences all number
    2
    2
    Spondylolisthesis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tendon calcification
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Tendonitis
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Periarthritis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hypothyroidism
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Thyroid cyst
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 196 (1.02%)
    1 / 197 (0.51%)
         occurrences all number
    2
    2
    Dehydration
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Diabetes mellitus
         subjects affected / exposed
    2 / 196 (1.02%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Dyslipidaemia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Fluid retention
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 196 (0.51%)
    4 / 197 (2.03%)
         occurrences all number
    1
    4
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 196 (1.53%)
    1 / 197 (0.51%)
         occurrences all number
    3
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Hypoglycaemia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Infections and infestations
    Acarodermatitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Acute sinusitis
         subjects affected / exposed
    1 / 196 (0.51%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Atypical mycobacterial infection
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    3 / 196 (1.53%)
    7 / 197 (3.55%)
         occurrences all number
    3
    7
    Cellulitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 196 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    4
    Cystitis
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Cystitis bacterial
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Diverticulitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Enteritis infectious
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Folliculitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 196 (1.02%)
    3 / 197 (1.52%)
         occurrences all number
    2
    3
    Genital herpes
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Gingivitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Infected bite
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    4 / 196 (2.04%)
    6 / 197 (3.05%)
         occurrences all number
    5
    7
    Laryngitis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    5 / 196 (2.55%)
    9 / 197 (4.57%)
         occurrences all number
    8
    9
    Oral herpes
         subjects affected / exposed
    3 / 196 (1.53%)
    2 / 197 (1.02%)
         occurrences all number
    3
    2
    Otitis externa fungal
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Paronychia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Pertussis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    4 / 196 (2.04%)
    4 / 197 (2.03%)
         occurrences all number
    4
    4
    Pneumonia
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Purulence
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    3 / 196 (1.53%)
    1 / 197 (0.51%)
         occurrences all number
    3
    1
    Rhinitis
         subjects affected / exposed
    1 / 196 (0.51%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Sinusitis
         subjects affected / exposed
    5 / 196 (2.55%)
    2 / 197 (1.02%)
         occurrences all number
    5
    2
    Skin infection
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Sycosis barbae
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Systemic infection
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    2
    Tracheitis
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Trichophytosis
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 196 (4.59%)
    5 / 197 (2.54%)
         occurrences all number
    14
    5
    Urinary tract infection
         subjects affected / exposed
    4 / 196 (2.04%)
    5 / 197 (2.54%)
         occurrences all number
    4
    5
    Viral infection
         subjects affected / exposed
    1 / 196 (0.51%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Viral pharyngitis
         subjects affected / exposed
    0 / 196 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    3
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 196 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2014
    Updated Section 8.2 to extend the SAE reporting period to 28 days after the last study visit.
    04 Dec 2014
    1. Deleted ADR table in Section 1.2.1.2 for MabThera and instead referenced the MabThera SPC to avoid any inconsistencies. 2. Updated Section 7.2.4 to clarify which laboratory tests were performed centrally and which were performed locally. 3. Clarified the vital signs which should be collected every 30 minutes during IP infusion (heart rate, seated blood pressure, respiratory rate, and oral or tympanic body temperature) and specified that a every 5 minute window is acceptable for the collection of vital signs during IP infusion. Sections impacted: Schedule of Assessments, Section 5.3.3 and Section 7.2.2.

    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
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