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    Clinical Trial Results:
    A Phase III, Open-label Extension Trial of ECU-MG-301 to Evaluate the Safety and Efficacy of Eculizumab in Subjects with Refractory Generalized Myasthenia Gravis (gMG)

    Summary
    EudraCT number
    		 2013-002191-41
    Trial protocol
    		 GB   IT   BE   DE   SE   HU   ES   NL   DK   CZ   FI  
    Global end of trial date
    15 Jan 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    04 Apr 2021
    First version publication date
    27 Dec 2019
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Aligned with ClinicalTrials.gov data

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ECU-MG-302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02301624
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alexion Pharmaceuticals, Inc.
    Sponsor organisation address
    121 Seaport Blvd, Boston, MA, United States, 02210
    Public contact
    European Clinical Trial Information, Alexion Europe SAS, +33 147100615, clinicaltrials.eu@alexion.com
    Scientific contact
    European Clinical Trial Information, Alexion Europe SAS, +33 147100615, clinicaltrials.eu@alexion.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
    11 Jun 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Jan 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jan 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and efficacy of eculizumab in the treatment of refractory generalized myasthenia gravis (gMG) as an extension study for the participants who completed Study ECU-MG-301 (2013-003589-15).
    Protection of trial subjects
    This study was conducted in accordance with the International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Nov 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    Denmark: 6
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Argentina: 6
    Country: Number of subjects enrolled
    Brazil: 6
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Japan: 11
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Turkey: 5
    Country: Number of subjects enrolled
    United States: 41
    Worldwide total number of subjects
    117
    EEA total number of subjects
    41
    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)
    97
    From 65 to 84 years
    20
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants who completed Study ECU-MG-301 (2013-003589-15) were eligible to participate in Study ECU-MG-302.

    Period 1
    Period 1 title
    Blind Induction Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The study consisted of a 4-week Blind Induction Phase to preserve the blinded nature of Study ECU-MG-301, followed by an Open-Label Maintenance Phase.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Blind Induction: Eculizumab/Eculizumab
    Arm description
    		 Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eculizumab was packed in a single 30-milliliter (mL) vial as a solution with a concentration of 10 mg/mL, with a unit dose of 300 mg in an intravenous infusion.

    Investigational medicinal product name
    Blind Induction: Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A clear, colorless solution in an identical 30-mL vial without the active ingredient.

    Arm title
    		 Blind Induction: Placebo/Eculizumab
    Arm description
    		 Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eculizumab was packed in a single 30-mL vial as a solution with a concentration of 10 mg/mL, with a unit dose of 300 mg in an intravenous infusion.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A clear, colorless solution in an identical 30-mL vial without the active ingredient.

    Number of subjects in period 1
    		Blind Induction: Eculizumab/Eculizumab Blind Induction: Placebo/Eculizumab
    Started
    56
    61
    Received at least 1 dose of study drug
    56
    61
    Completed
    55
    61
    Not completed
    1
    0
         Consent withdrawn by subject
    1
    -
    Period 2
    Period 2 title
    Open-label Maintenance Phase
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Open-label: Eculizumab/Eculizumab
    Arm description
    		 Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    All participants received eculizumab 1200 mg every 2 weeks during the Open-Label Maintenance Phase. Eculizumab was packed in a single 30-mL vial as a solution with a concentration of 10 mg/mL, with a unit dose of 300 mg in an intravenous infusion.

    Arm title
    		 Open-label: Placebo/Eculizumab
    Arm description
    		 Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    All participants received eculizumab 1200 mg every 2 weeks during the Open-Label Maintenance Phase. Eculizumab was packed in a single 30-mL vial as a solution with a concentration of 10 mg/mL, with a unit dose of 300 mg in an intravenous infusion.

    Number of subjects in period 2
    		Open-label: Eculizumab/Eculizumab Open-label: Placebo/Eculizumab
    Started
    55
    61
    Received at least 1 dose of study drug
    55
    61
    Completed
    43
    44
    Not completed
    12
    17
         Physician decision
    3
    3
         Consent withdrawn by subject
    4
    8
         Adverse event, non-fatal
    2
    5
         Death
    2
    1
         Participant felt no change in condition
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Blind Induction: Eculizumab/Eculizumab
    Reporting group description
    		 Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3.

    Reporting group title
    Blind Induction: Placebo/Eculizumab
    Reporting group description
    		 Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3.

    Reporting group values
    		 Blind Induction: Eculizumab/Eculizumab Blind Induction: Placebo/Eculizumab Total
    Number of subjects
    		 56 61 117
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 47 50 97
        From 65-84 years
    		 9 11 20
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 47.2 ± 15.52 47.5 ± 17.85 -
    Gender categorical
    Units: Subjects
        Female
    		 38 41 79
        Male
    		 18 20 38
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 8 10 18
        Not Hispanic or Latino
    		 45 48 93
        Unknown or Not Reported
    		 3 3 6
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 3 16 19
        Black or African American
    		 0 2 2
        White
    		 47 41 88
        Multiple
    		 1 0 1
        Unknown
    		 1 0 1
        Other
    		 4 2 6

    End points

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    End points reporting groups
    Reporting group title
    Blind Induction: Eculizumab/Eculizumab
    Reporting group description
    		 Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3.

    Reporting group title
    Blind Induction: Placebo/Eculizumab
    Reporting group description
    		 Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3.
    Reporting group title
    Open-label: Eculizumab/Eculizumab
    Reporting group description
    		 Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Reporting group title
    Open-label: Placebo/Eculizumab
    Reporting group description
    		 Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Subject analysis set title
    Eculizumab/Eculizumab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Subject analysis set title
    Placebo/Eculizumab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study

    Primary: Count Of Participants With Treatment-emergent Adverse Events

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    End point title
    		 Count Of Participants With Treatment-emergent Adverse Events [1]
    End point description
    Treatment-emergent adverse events (TEAEs) are adverse events with onset on or after the first study drug dose in Study ECU-MG-302. Likewise, treatment-emergent serious adverse events (TESAEs) are serious adverse events that onset on or after the first study drug dose in Study ECU-MG-302. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Adverse events module.
    End point type
    Primary
    End point timeframe
    Day 1 (after dosing) through End of Study (Week 208)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were planned.
    End point values
    		 Eculizumab/Eculizumab Placebo/Eculizumab
    Number of subjects analysed
    56
    61
    Units: Participants
        TEAEs
    55
    59
        TEAEs leading to withdrawal
    3
    5
        TESAEs
    30
    30
        TESAEs leading to withdrawal
    3
    4
        Deaths
    2
    1
    No statistical analyses for this end point

    Secondary: Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 and Week 130

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    End point title
    		 Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 and Week 130
    End point description
    The MG-ADL scale is a validated 8-item patient-reported outcome measure. Participants assessed their functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb impairment (2 items). These 8 items were not weighted and were individually graded from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24 points. A reduction in score indicates improvement in condition. Baseline was defined as the last available assessment prior to treatment (first study drug infusion) with eculizumab in Study ECU-MG-302. Change from Baseline in MG-ADL total score at Week 4 (blind induction phase) and at Week 130 (open-label eculizumab phase) are presented.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4 and Week 130
    End point values
    		 Eculizumab/Eculizumab Placebo/Eculizumab
    Number of subjects analysed
    55 [2]
    61 [3]
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Change from Baseline at Week 4 (Blind Induction)
    -0.2 ± 1.77
    -2.4 ± 3.04
        Change from Baseline at Week 130 (Open-label)
    -0.7 ± 4.19
    -3.9 ± 3.68
    Notes
    [2] - Week 4 (N=55); Week 130 (N=35)
    [3] - Week 4 (N=61); Week 130 (N=36)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 after dosing of study drug through Week 208.
    Adverse event reporting additional description
    All eligible-enrolled participants who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Eculizumab/Eculizumab
    Reporting group description
    		 Blind Induction: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 mg) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Reporting group title
    Placebo/Eculizumab
    Reporting group description
    		 Blind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Reporting group title
    Eculizumab (Combined Total)
    Reporting group description
    		 All participants who received at least 1 dose of eculizumab in the extension study. Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.

    Serious adverse events
    		 Eculizumab/Eculizumab Placebo/Eculizumab Eculizumab (Combined Total)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    30 / 56 (53.57%)
    30 / 61 (49.18%)
    60 / 117 (51.28%)
         number of deaths (all causes)
    2
    1
    3
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 61 (1.64%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed [1]
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin papilloma
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Arterial occlusive disease
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lupus vasculitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 61 (0.00%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Autoimmune disorder
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed [2]
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed [3]
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed [4]
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 56 (0.00%)
    3 / 61 (4.92%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 61 (3.28%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 56 (0.00%)
    3 / 61 (4.92%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Respiratory distress
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrostomy tube site complication
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    2 / 56 (3.57%)
    0 / 61 (0.00%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 61 (3.28%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    7 / 56 (12.50%)
    9 / 61 (14.75%)
    16 / 117 (13.68%)
         occurrences causally related to treatment / all
    2 / 13
    3 / 16
    6 / 29
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis crisis
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 61 (3.28%)
    4 / 117 (3.42%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriparesis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 56 (3.57%)
    1 / 61 (1.64%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal incarcerated hernia
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Chronic hepatic failure
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatic failure
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 61 (1.64%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis reactive
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture nonunion
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asymptomatic bacteriuria
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 61 (1.64%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bursitis infective staphylococcal
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic abscess
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 61 (3.28%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 56 (3.57%)
    0 / 61 (0.00%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 61 (1.64%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis meningococcal
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 61 (3.28%)
    4 / 117 (3.42%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 56 (3.57%)
    1 / 61 (1.64%)
    3 / 117 (2.56%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 61 (1.64%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 61 (3.28%)
    2 / 117 (1.71%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Central obesity
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 61 (1.64%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 61 (0.00%)
    1 / 117 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Adverse event affected male participants only.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Adverse event affected female participants only.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Adverse event affected female participants only.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Adverse event affected female participants only.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Eculizumab/Eculizumab Placebo/Eculizumab Eculizumab (Combined Total)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    54 / 56 (96.43%)
    59 / 61 (96.72%)
    113 / 117 (96.58%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 61 (6.56%)
    6 / 117 (5.13%)
         occurrences all number
    2
    19
    21
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 56 (10.71%)
    0 / 61 (0.00%)
    6 / 117 (5.13%)
         occurrences all number
    8
    0
    8
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    8 / 56 (14.29%)
    7 / 61 (11.48%)
    15 / 117 (12.82%)
         occurrences all number
    9
    7
    16
    Pyrexia
         subjects affected / exposed
    5 / 56 (8.93%)
    8 / 61 (13.11%)
    13 / 117 (11.11%)
         occurrences all number
    5
    14
    19
    Influenza like illness
         subjects affected / exposed
    4 / 56 (7.14%)
    3 / 61 (4.92%)
    7 / 117 (5.98%)
         occurrences all number
    4
    7
    11
    Oedema peripheral
         subjects affected / exposed
    4 / 56 (7.14%)
    3 / 61 (4.92%)
    7 / 117 (5.98%)
         occurrences all number
    6
    4
    10
    Chest pain
         subjects affected / exposed
    4 / 56 (7.14%)
    2 / 61 (3.28%)
    6 / 117 (5.13%)
         occurrences all number
    5
    2
    7
    Peripheral swelling
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    3
    2
    5
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    3 / 56 (5.36%)
    7 / 61 (11.48%)
    10 / 117 (8.55%)
         occurrences all number
    4
    8
    12
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed [5]
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    3 / 79 (3.80%)
         occurrences all number
    4
    0
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 56 (21.43%)
    10 / 61 (16.39%)
    22 / 117 (18.80%)
         occurrences all number
    15
    13
    28
    Oropharyngeal pain
         subjects affected / exposed
    3 / 56 (5.36%)
    9 / 61 (14.75%)
    12 / 117 (10.26%)
         occurrences all number
    4
    11
    15
    Asthma
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    6
    2
    8
    Productive cough
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    4
    4
    8
    Psychiatric disorders
    Depression
         subjects affected / exposed
    3 / 56 (5.36%)
    8 / 61 (13.11%)
    11 / 117 (9.40%)
         occurrences all number
    3
    10
    13
    Insomnia
         subjects affected / exposed
    7 / 56 (12.50%)
    2 / 61 (3.28%)
    9 / 117 (7.69%)
         occurrences all number
    7
    2
    9
    Anxiety
         subjects affected / exposed
    4 / 56 (7.14%)
    4 / 61 (6.56%)
    8 / 117 (6.84%)
         occurrences all number
    5
    4
    9
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    8 / 56 (14.29%)
    6 / 61 (9.84%)
    14 / 117 (11.97%)
         occurrences all number
    16
    11
    27
    Contusion
         subjects affected / exposed
    7 / 56 (12.50%)
    5 / 61 (8.20%)
    12 / 117 (10.26%)
         occurrences all number
    15
    8
    23
    Infusion related reaction
         subjects affected / exposed
    4 / 56 (7.14%)
    7 / 61 (11.48%)
    11 / 117 (9.40%)
         occurrences all number
    9
    31
    40
    Procedural pain
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 61 (6.56%)
    6 / 117 (5.13%)
         occurrences all number
    5
    4
    9
    Ligament sprain
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    4
    2
    6
    Tooth fracture
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    3
    1
    4
    Rib fracture
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 61 (0.00%)
    3 / 117 (2.56%)
         occurrences all number
    3
    0
    3
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    4 / 56 (7.14%)
    2 / 61 (3.28%)
    6 / 117 (5.13%)
         occurrences all number
    4
    5
    9
    Atrial fibrillation
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 61 (1.64%)
    5 / 117 (4.27%)
         occurrences all number
    5
    1
    6
    Palpitations
         subjects affected / exposed
    1 / 56 (1.79%)
    4 / 61 (6.56%)
    5 / 117 (4.27%)
         occurrences all number
    1
    4
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    20 / 56 (35.71%)
    24 / 61 (39.34%)
    44 / 117 (37.61%)
         occurrences all number
    31
    41
    72
    Myasthenia gravis
         subjects affected / exposed
    12 / 56 (21.43%)
    5 / 61 (8.20%)
    17 / 117 (14.53%)
         occurrences all number
    15
    5
    20
    Dizziness
         subjects affected / exposed
    3 / 56 (5.36%)
    6 / 61 (9.84%)
    9 / 117 (7.69%)
         occurrences all number
    7
    7
    14
    Migraine
         subjects affected / exposed
    4 / 56 (7.14%)
    3 / 61 (4.92%)
    7 / 117 (5.98%)
         occurrences all number
    4
    3
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 56 (8.93%)
    3 / 61 (4.92%)
    8 / 117 (6.84%)
         occurrences all number
    6
    3
    9
    Iron deficiency anaemia
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    3
    2
    5
    Lymphopenia
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 61 (0.00%)
    3 / 117 (2.56%)
         occurrences all number
    3
    0
    3
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    3 / 56 (5.36%)
    4 / 61 (6.56%)
    7 / 117 (5.98%)
         occurrences all number
    4
    5
    9
    Ear pain
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 61 (6.56%)
    6 / 117 (5.13%)
         occurrences all number
    3
    4
    7
    Eye disorders
    Cataract
         subjects affected / exposed
    4 / 56 (7.14%)
    5 / 61 (8.20%)
    9 / 117 (7.69%)
         occurrences all number
    5
    5
    10
    Dry eye
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 61 (6.56%)
    6 / 117 (5.13%)
         occurrences all number
    2
    4
    6
    Eye pain
         subjects affected / exposed
    0 / 56 (0.00%)
    4 / 61 (6.56%)
    4 / 117 (3.42%)
         occurrences all number
    0
    4
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    15 / 56 (26.79%)
    14 / 61 (22.95%)
    29 / 117 (24.79%)
         occurrences all number
    20
    23
    43
    Nausea
         subjects affected / exposed
    9 / 56 (16.07%)
    13 / 61 (21.31%)
    22 / 117 (18.80%)
         occurrences all number
    13
    14
    27
    Abdominal discomfort
         subjects affected / exposed
    4 / 56 (7.14%)
    6 / 61 (9.84%)
    10 / 117 (8.55%)
         occurrences all number
    4
    6
    10
    Vomiting
         subjects affected / exposed
    3 / 56 (5.36%)
    7 / 61 (11.48%)
    10 / 117 (8.55%)
         occurrences all number
    3
    10
    13
    Abdominal pain upper
         subjects affected / exposed
    2 / 56 (3.57%)
    6 / 61 (9.84%)
    8 / 117 (6.84%)
         occurrences all number
    2
    6
    8
    Toothache
         subjects affected / exposed
    3 / 56 (5.36%)
    5 / 61 (8.20%)
    8 / 117 (6.84%)
         occurrences all number
    5
    6
    11
    Dental caries
         subjects affected / exposed
    2 / 56 (3.57%)
    5 / 61 (8.20%)
    7 / 117 (5.98%)
         occurrences all number
    3
    5
    8
    Dyspepsia
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 61 (6.56%)
    6 / 117 (5.13%)
         occurrences all number
    2
    5
    7
    Abdominal pain
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    3
    3
    6
    Tooth disorder
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 61 (0.00%)
    3 / 117 (2.56%)
         occurrences all number
    3
    0
    3
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    4 / 56 (7.14%)
    4 / 61 (6.56%)
    8 / 117 (6.84%)
         occurrences all number
    4
    4
    8
    Eczema
         subjects affected / exposed
    3 / 56 (5.36%)
    3 / 61 (4.92%)
    6 / 117 (5.13%)
         occurrences all number
    3
    3
    6
    Rash
         subjects affected / exposed
    3 / 56 (5.36%)
    3 / 61 (4.92%)
    6 / 117 (5.13%)
         occurrences all number
    4
    5
    9
    Alopecia
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    3
    2
    5
    Urticaria
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    3
    1
    4
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    3
    1
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 56 (19.64%)
    12 / 61 (19.67%)
    23 / 117 (19.66%)
         occurrences all number
    18
    13
    31
    Pain in extremity
         subjects affected / exposed
    9 / 56 (16.07%)
    8 / 61 (13.11%)
    17 / 117 (14.53%)
         occurrences all number
    12
    9
    21
    Back pain
         subjects affected / exposed
    5 / 56 (8.93%)
    7 / 61 (11.48%)
    12 / 117 (10.26%)
         occurrences all number
    7
    11
    18
    Muscle spasms
         subjects affected / exposed
    5 / 56 (8.93%)
    6 / 61 (9.84%)
    11 / 117 (9.40%)
         occurrences all number
    7
    6
    13
    Neck pain
         subjects affected / exposed
    5 / 56 (8.93%)
    4 / 61 (6.56%)
    9 / 117 (7.69%)
         occurrences all number
    5
    4
    9
    Musculoskeletal pain
         subjects affected / exposed
    3 / 56 (5.36%)
    4 / 61 (6.56%)
    7 / 117 (5.98%)
         occurrences all number
    3
    4
    7
    Myalgia
         subjects affected / exposed
    5 / 56 (8.93%)
    7 / 61 (11.48%)
    12 / 117 (10.26%)
         occurrences all number
    8
    19
    27
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    20 / 56 (35.71%)
    22 / 61 (36.07%)
    42 / 117 (35.90%)
         occurrences all number
    36
    49
    85
    Upper respiratory tract infection
         subjects affected / exposed
    12 / 56 (21.43%)
    15 / 61 (24.59%)
    27 / 117 (23.08%)
         occurrences all number
    34
    28
    62
    Influenza
         subjects affected / exposed
    11 / 56 (19.64%)
    10 / 61 (16.39%)
    21 / 117 (17.95%)
         occurrences all number
    15
    14
    29
    Urinary tract infection
         subjects affected / exposed
    10 / 56 (17.86%)
    8 / 61 (13.11%)
    18 / 117 (15.38%)
         occurrences all number
    13
    18
    31
    Bronchitis
         subjects affected / exposed
    6 / 56 (10.71%)
    7 / 61 (11.48%)
    13 / 117 (11.11%)
         occurrences all number
    15
    7
    22
    Gastroenteritis
         subjects affected / exposed
    6 / 56 (10.71%)
    5 / 61 (8.20%)
    11 / 117 (9.40%)
         occurrences all number
    7
    6
    13
    Sinusitis
         subjects affected / exposed
    7 / 56 (12.50%)
    4 / 61 (6.56%)
    11 / 117 (9.40%)
         occurrences all number
    20
    4
    24
    Gastroenteritis viral
         subjects affected / exposed
    4 / 56 (7.14%)
    6 / 61 (9.84%)
    10 / 117 (8.55%)
         occurrences all number
    4
    9
    13
    Pneumonia
         subjects affected / exposed
    4 / 56 (7.14%)
    6 / 61 (9.84%)
    10 / 117 (8.55%)
         occurrences all number
    4
    8
    12
    Cellulitis
         subjects affected / exposed
    4 / 56 (7.14%)
    4 / 61 (6.56%)
    8 / 117 (6.84%)
         occurrences all number
    6
    5
    11
    Oral herpes
         subjects affected / exposed
    3 / 56 (5.36%)
    3 / 61 (4.92%)
    6 / 117 (5.13%)
         occurrences all number
    6
    4
    10
    Tonsillitis
         subjects affected / exposed
    1 / 56 (1.79%)
    4 / 61 (6.56%)
    5 / 117 (4.27%)
         occurrences all number
    1
    6
    7
    Herpes zoster
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    3
    1
    4
    Respiratory tract infection
         subjects affected / exposed
    4 / 56 (7.14%)
    0 / 61 (0.00%)
    4 / 117 (3.42%)
         occurrences all number
    6
    0
    6
    Pharyngitis
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 61 (0.00%)
    3 / 117 (2.56%)
         occurrences all number
    4
    0
    4
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 61 (3.28%)
    5 / 117 (4.27%)
         occurrences all number
    3
    2
    5
    Dehydration
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 61 (1.64%)
    4 / 117 (3.42%)
         occurrences all number
    3
    1
    4
    Notes
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Adverse event affected female participants only.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jun 2015
    Protocol Amendment 1 (Global) included the following significant changes from the original protocol: • An allowance for interim analyses was added to the protocol to provide long-term safety and efficacy data for this ongoing study. • Exclusion criteria for unresolved meningococcal infection and for hypersensitivity to murine proteins or to one of the excipients in eculizumab were added to protect participant safety.
    19 Dec 2016
    Protocol Amendment 2 (Global) included the following significant changes from the original protocol: • The addition of a post-treatment follow-up to allow the Sponsor to collect information concerning MG status in participants post-treatment up to 1 year from the end-of-study/early termination visit. • The addition of Appendix 11 to the protocol to provide further details regarding the post-treatment information collection, including: 1. Study participants will be provided an updated informed consent form (ICF) (and/or ICF Addendum) for consent to post-treatment information collection by the Sponsor. 2. Summarizing the reason for collecting follow-up information, what information will be collected, the route(s) through which the information may be collected, and how the information will be used.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30767274
    http://www.ncbi.nlm.nih.gov/pubmed/31115842
    http://www.ncbi.nlm.nih.gov/pubmed/30905021
    http://www.ncbi.nlm.nih.gov/pubmed/31698177
    For support, Contact us.
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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