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    Clinical Trial Results:
    Protocol I4T-MC-JVCZ Randomized Phase 2 Trial Evaluating Alternative Ramucirumab Doses in Combination with Paclitaxel in Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma

    Summary
    EudraCT number
    		 2014-005067-32
    Trial protocol
    		 DE   CZ   SE   GR   BE   ES  
    Global end of trial date
    28 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Jan 2020
    First version publication date
    05 Jan 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4T-MC-JVCZ
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02514551
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 15541
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    28 Dec 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study is to evaluate the efficacy of an alternative dose of ramucirumab in combination with paclitaxel in participants with second-line metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma (GEJ).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (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 a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Oct 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 21 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Greece: 21
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Turkey: 40
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    United States: 24
    Country: Number of subjects enrolled
    Ukraine: 44
    Country: Number of subjects enrolled
    Italy: 23
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Spain: 56
    Country: Number of subjects enrolled
    Czech Republic: 16
    Worldwide total number of subjects
    245
    EEA total number of subjects
    133
    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)
    165
    From 65 to 84 years
    80
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Available

    Pre-assignment
    Screening details
    		 Completers are defined as participants who died or had progressive disease (PD) or completed treatment or did not complete treatment and were followed for survival data. Final study data will be provided after study completion.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm description
    		 12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    Other name
    LY3009806,IMC-1121B,Cyramza
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles)

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.

    Arm title
    		 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm description
    		 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    Other name
    LY3009806, IMC-1121B
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles).

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Number of subjects in period 1
    		12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Started
    123
    122
    Received at least one dose of study drug
    123
    120
    Completed
    123
    119
    Not completed
    0
    3
         Participant Never Treated
    -
    2
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.

    Reporting group title
    8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Reporting group values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel Total
    Number of subjects
    		 123 122 245
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 83 82 165
        Adults (65-84 years)
    		 40 40 80
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.6 ± 11.4 57.9 ± 12.3 -
    Gender categorical
    Units: Subjects
        Female
    		 40 44 84
        Male
    		 83 78 161
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 8 7 15
        Not Hispanic or Latino
    		 110 108 218
        Unknown or Not Reported
    		 5 7 12
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 0 3 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 2 2 4
        White
    		 119 117 236
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 1 0 1
    Region of Enrollment
    Units: Subjects
        Greece
    		 10 11 21
        Canada
    		 0 4 4
        Sweden
    		 1 1 2
        Turkey
    		 24 16 40
        Belgium
    		 6 5 11
        United States
    		 16 8 24
        Czechia
    		 7 9 16
        Ukraine
    		 18 26 44
        Italy
    		 16 7 23
        Germany
    		 2 2 4
        Spain
    		 23 33 56

    End points

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    End points reporting groups
    Reporting group title
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.

    Reporting group title
    8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Subject analysis set title
    I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Primary: Progression Free Survival (PFS) in Ramucirumab 12mg/kg arm I4T-MC-JVCZ

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    End point title
    		 Progression Free Survival (PFS) in Ramucirumab 12mg/kg arm I4T-MC-JVCZ [1]
    End point description
    PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later). This analysis were comparison of PFS for participants treated with ramucirumab 12 mg/kg plus paclitaxel in Study I4T-MC-JVCZ versus placebo plus paclitaxel in I4T-IE-JVBE (NCT01170663) using meta-analysis. Placebo + 80 mg/m² Paclitaxel in I4T-IE-JVBE Number of participants: 335, Median (95% CI), months: 2.86 (2.79 to 3.02). Hazard Ratio (HR) = 0.617, 2 sided Confidence Interval (0.447 to 0.853 ). HR was estimated by Unstratified cox proportional hazards model comparing Ramucirumab I4T-MC-JVCZ and I4T-IE-JVBE (NCT01170663).
    End point type
    Primary
    End point timeframe
    Randomization to Objective Progressive Disease or Death (Up To 21 Months) Analysis Population Description (APD). All randomized participants in arm 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel. Censored: Ramucirumab 12 mg/kg + 80 mg/m² Paclitaxel= 25.
    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: Statistical analysis are reported in the outcome measure description. This was a meta-analysis of two studies JVCZ and JVBE. There is no JVBE arm in the participant flow hence comparison data cannot be reported in the statistical analysis section.
    End point values
    		 I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    123
    Units: months
        median (confidence interval 95%)
    5.42 (4.40 to 6.01)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ

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    End point title
    		 Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ
    End point description
    PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.
    End point type
    Secondary
    End point timeframe
    Randomization to Objective Progressive Disease or Death (Up To 21 Months) APD: All randomized participants. Censored: Ramucirumab 12 mg/kg + Paclitaxel 80 mg/m2= 25 and 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel =23.
    End point values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    123
    122
    Units: months
        median (confidence interval 95%)
    5.42 (4.40 to 6.01)
    5.16 (3.81 to 5.65)
    Statistical analysis title
    		 Progression Free Survival (PFS) Ramucirumab 12mg/
    Comparison groups
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel v 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects included in analysis
    245
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.963
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.727
         upper limit
    		 1.274

    Secondary: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel

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    End point title
    		 Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel
    End point description
    Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel. Analysis Population Description: All randomized participants who received at least one dose of study drug and had evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI
    End point values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    103
    95
    Units: Microgram per milliliter (µg/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 15 (Week 2)
    39.2 ± 43
    21.4 ± 58
        Cycle 2 Day 1 (Week 4)
    63.6 ± 40
    37.1 ± 50
        Cycle 2 Day 15 (Week 6)
    76.7 ± 42
    43.5 ± 53
        Cycle 3 Day 1(Week 8)
    91.2 ± 40
    51.5 ± 55
        Cycle 3 Day 15 (Week 10)
    99.0 ± 44
    52.9 ± 56
        Cycle 4 Day 1 (Week 12)
    101 ± 55
    56.1 ± 56
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])

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    End point title
    		 Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])
    End point description
    ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. Analysis Population Description: All randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Progressive Disease (Up To 21 Months)
    End point values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    123
    122
    Units: percentage of participants
        number (not applicable)
    27.6
    25.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)]

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    End point title
    		 Percentage of Participants who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)]
    End point description
    DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions. DCR=CR+PR+SD/total number of participants*100.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Progressive Disease (Up To 21 Months) Analysis Population Description: All randomized participants.
    End point values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    123
    122
    Units: percentage of participants
        number (not applicable)
    78.9
    75.4
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-Ramucirumab Antibodies

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    End point title
    		 Number of Participants with Anti-Ramucirumab Antibodies
    End point description
    Participants who had anti-ramucirumab antibodies at postbaseline. Analysis Population Description: All randomized participants who received at least one dose of study drug and were evaluable for ramucirumab anti-drug antibody.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Predose through Follow-up (Up To 24 Months)
    End point values
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Number of subjects analysed
    105
    89
    Units: participants
    2
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up T0 40 Months
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Reporting group title
    8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Reporting group description
    		 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

    Serious adverse events
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    47 / 123 (38.21%)
    32 / 120 (26.67%)
         number of deaths (all causes)
    10
    8
         number of deaths resulting from adverse events
    5
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    lymphangiosis carcinomatosa
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour perforation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Vascular disorders
    hypotension
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    shock haemorrhagic
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    localised oedema
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malaise
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    organ failure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    oedema genital
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    aspiration
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    dyspnoea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hiccups
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    pneumothorax
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary hypertension
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory distress
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Investigations
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood bilirubin increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutrophil count decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    6 / 123 (4.88%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    femoral neck fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infusion related reaction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    cardiac failure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiopulmonary failure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cardiovascular insufficiency
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    syncope
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    3 / 123 (2.44%)
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bone marrow failure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    febrile neutropenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    4 / 123 (3.25%)
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    leukocytosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    4 / 123 (3.25%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ascites
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysphagia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    3 / 123 (2.44%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    5 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric perforation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric stenosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematemesis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ileus
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestinal haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal fistula
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    oesophageal haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal obstruction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal perforation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumoperitoneum
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tongue oedema
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    vomiting
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    3 / 123 (2.44%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholangitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gallbladder rupture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatitis toxic
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    proteinuria
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (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
    back pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    bacteraemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    clostridium difficile colitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enteritis infectious
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    escherichia infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 123 (1.63%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia necrotising
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    cachexia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    decreased appetite
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 123 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperkalaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypokalaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malnutrition
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 123 (0.81%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    117 / 123 (95.12%)
    115 / 120 (95.83%)
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    14 / 123 (11.38%)
    7 / 120 (5.83%)
         occurrences all number
    27
    8
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    20 / 123 (16.26%)
    8 / 120 (6.67%)
         occurrences all number
    43
    15
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    10 / 120 (8.33%)
         occurrences all number
    25
    14
    blood bilirubin increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    8 / 123 (6.50%)
    2 / 120 (1.67%)
         occurrences all number
    12
    3
    neutrophil count decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    30 / 123 (24.39%)
    24 / 120 (20.00%)
         occurrences all number
    91
    60
    platelet count decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    7 / 120 (5.83%)
         occurrences all number
    15
    13
    weight decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    14 / 123 (11.38%)
    13 / 120 (10.83%)
         occurrences all number
    16
    17
    white blood cell count decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    13 / 123 (10.57%)
    14 / 120 (11.67%)
         occurrences all number
    33
    35
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    24 / 123 (19.51%)
    21 / 120 (17.50%)
         occurrences all number
    44
    46
    Nervous system disorders
    dysgeusia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    5 / 123 (4.07%)
    9 / 120 (7.50%)
         occurrences all number
    5
    13
    headache
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    10 / 123 (8.13%)
    9 / 120 (7.50%)
         occurrences all number
    12
    12
    neuropathy peripheral
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    15 / 123 (12.20%)
    15 / 120 (12.50%)
         occurrences all number
    38
    22
    paraesthesia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    13 / 123 (10.57%)
    13 / 120 (10.83%)
         occurrences all number
    30
    29
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    8 / 123 (6.50%)
    20 / 120 (16.67%)
         occurrences all number
    15
    46
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    34 / 123 (27.64%)
    39 / 120 (32.50%)
         occurrences all number
    72
    77
    leukopenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    9 / 120 (7.50%)
         occurrences all number
    44
    18
    neutropenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    22 / 123 (17.89%)
    24 / 120 (20.00%)
         occurrences all number
    78
    62
    thrombocytopenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    7 / 123 (5.69%)
    4 / 120 (3.33%)
         occurrences all number
    10
    5
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    15 / 123 (12.20%)
    19 / 120 (15.83%)
         occurrences all number
    35
    49
    fatigue
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    43 / 123 (34.96%)
    46 / 120 (38.33%)
         occurrences all number
    85
    82
    oedema peripheral
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    10 / 123 (8.13%)
    16 / 120 (13.33%)
         occurrences all number
    11
    22
    pyrexia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    8 / 120 (6.67%)
         occurrences all number
    10
    8
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    7 / 123 (5.69%)
    6 / 120 (5.00%)
         occurrences all number
    9
    8
    abdominal pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    20 / 123 (16.26%)
    19 / 120 (15.83%)
         occurrences all number
    31
    22
    abdominal pain upper
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    8 / 123 (6.50%)
    12 / 120 (10.00%)
         occurrences all number
    13
    16
    ascites
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    5 / 120 (4.17%)
         occurrences all number
    11
    8
    constipation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    23 / 123 (18.70%)
    21 / 120 (17.50%)
         occurrences all number
    33
    27
    diarrhoea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    31 / 123 (25.20%)
    35 / 120 (29.17%)
         occurrences all number
    78
    65
    dysphagia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    11 / 123 (8.94%)
    4 / 120 (3.33%)
         occurrences all number
    12
    4
    nausea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    27 / 123 (21.95%)
    38 / 120 (31.67%)
         occurrences all number
    52
    95
    stomatitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    15 / 123 (12.20%)
    18 / 120 (15.00%)
         occurrences all number
    19
    41
    vomiting
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    29 / 123 (23.58%)
    27 / 120 (22.50%)
         occurrences all number
    51
    44
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    14 / 123 (11.38%)
    8 / 120 (6.67%)
         occurrences all number
    17
    11
    dysphonia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    11 / 123 (8.94%)
    6 / 120 (5.00%)
         occurrences all number
    15
    7
    dyspnoea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    4 / 123 (3.25%)
    12 / 120 (10.00%)
         occurrences all number
    5
    13
    epistaxis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    26 / 123 (21.14%)
    28 / 120 (23.33%)
         occurrences all number
    43
    36
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    19 / 123 (15.45%)
    24 / 120 (20.00%)
         occurrences all number
    19
    28
    Renal and urinary disorders
    proteinuria
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    9 / 123 (7.32%)
    8 / 120 (6.67%)
         occurrences all number
    19
    11
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    8 / 123 (6.50%)
    5 / 120 (4.17%)
         occurrences all number
    13
    5
    back pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    10 / 123 (8.13%)
    9 / 120 (7.50%)
         occurrences all number
    13
    14
    myalgia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    11 / 123 (8.94%)
    9 / 120 (7.50%)
         occurrences all number
    18
    16
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    25 / 123 (20.33%)
    32 / 120 (26.67%)
         occurrences all number
    41
    58
    hyperglycaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    8 / 123 (6.50%)
    11 / 120 (9.17%)
         occurrences all number
    18
    20
    hypoalbuminaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    10 / 123 (8.13%)
    14 / 120 (11.67%)
         occurrences all number
    13
    34
    hyponatraemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    7 / 123 (5.69%)
    7 / 120 (5.83%)
         occurrences all number
    13
    8

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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    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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