Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) with or without Durvalumab in Combination with Chemotherapy in Subjects with Metastatic Pancreatic Ductal Adenocarcinoma

    Summary
    EudraCT number
    		 2018-001028-21
    Trial protocol
    		 NO   ES  
    Global end of trial date
    22 Jul 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    24 Sep 2023
    First version publication date
    03 Aug 2023
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D6070C00005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03611556
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, Maryland, United States, 20878
    Public contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.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 Nov 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study are: 1. To assess the safety and tolerability of oleclumab (Ole) plus durvalumab (Durva) in combination with chemotherapy administered in participants with metastatic pancreatic ductal adenocarcinoma (PDAC) in dose escalation phase (Part 1). 2. To evaluate the preliminary antitumor activity of ole with or without durva in combination with gemcitabine (Gem) and nab-paclitaxel (nab-pacli) compared to gem and nab-pacli administered in participants with first-line metastatic PDAC in dose expansion phase (Part 2). 3. To evaluate the preliminary antitumor activity of ole with or without durva in combination with modified regimen of leucovorin (folinic acid), 5-fluorouracil, and oxaliplatin (mFOLFOX) compared to mFOLFOX administered in participants with second-line (2L) metastatic PDAC in dose expansion phase (Part 2).
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Jun 2018
    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
    Australia: 21
    Country: Number of subjects enrolled
    Norway: 4
    Country: Number of subjects enrolled
    Spain: 24
    Country: Number of subjects enrolled
    United States: 146
    Worldwide total number of subjects
    195
    EEA total number of subjects
    28
    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)
    102
    From 65 to 84 years
    92
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 29 sites in 4 countries (Australia, Norway, Spain, and the United States of America).

    Pre-assignment
    Screening details
    		 A total of 25 participants were treated in dose escalation part of this study. A total of 188 participants were randomized in dose expansion part of this study of which 170 participants were treated (18 participants were randomized but not treated). Results are presented for 195 treated participants only.

    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
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) until disease progression (PD), intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Arm description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    mFOLFOX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Arm description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    mFOLFOX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Number of subjects in period 1
    		Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Started
    7
    7
    3
    8
    62
    38
    70
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    7
    7
    3
    8
    62
    38
    70
         Adverse event, serious fatal
    1
    -
    -
    -
    3
    1
    3
         Death due to disease progression
    6
    7
    3
    8
    42
    31
    49
         Death due to toxicity related to study drug
    -
    -
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    -
    -
    -
    -
    4
    2
    4
         Death, reason unspecified
    -
    -
    -
    -
    2
    -
    -
         Sponsor decision
    -
    -
    -
    -
    9
    4
    12
         Reasons
    -
    -
    -
    -
    2
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli Total
    Number of subjects
    		 7 7 3 8 62 38 70 195
    Age categorical
    Units: Participants
        In utero
    		 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 2 4 1 3 29 23 40 102
        From 65-84 years
    		 5 3 2 5 32 15 30 92
        85 years and over
    		 0 0 0 0 1 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 66.7 ( 12.8 ) 59.6 ( 11.4 ) 67.0 ( 14.9 ) 64.8 ( 4.8 ) 65.6 ( 8.0 ) 62.5 ( 11.1 ) 62.9 ( 8.3 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 3 4 1 4 26 17 34 89
        Male
    		 4 3 2 4 36 21 36 106
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 1 1
        Asian
    		 0 0 0 0 5 1 1 7
        Native Hawaiian or Other Pacific Islander
    		 1 0 0 0 0 0 0 1
        Black or African American
    		 0 1 0 2 3 2 2 10
        White
    		 6 5 3 6 54 33 64 171
        More than one race
    		 0 1 0 0 0 1 0 2
        Unknown or Not Reported
    		 0 0 0 0 0 1 2 3
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 1 0 1 1 3
        Not Hispanic or Latino
    		 7 7 3 7 61 37 69 191
        Unknown or Not Reported
    		 0 0 0 0 1 0 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase [1] [2]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    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 was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Any TEAEs
    7
    7
    3
    8
        Any TESAEs
    4
    6
    0
    4
    No statistical analyses for this end point

    Primary: Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase [3] [4]
    End point description
    DLT: Any study drug related Grade (G)3/higher toxicity including: any G4 immune-mediated AEs,>=G3 colitis/pneumonitis(PN)/interstitial lung disease (ILD),>=G3 nausea/vomiting/diarrhea that did not resolve to G2/less in 3 days of maximal supportive care (MSC), G2 PN/ILD that did not resolve in 7 days of starting MSC, G4 anemia, G3 anemia with clinical sequelae/>2 units of red blood cells transfusion, G4 thrombocytopenia(TP)/neutropenia>=7 days, G3/4 TP with >=G3 hemorrhage, G4 febrile neutropenia(FN), G3 FN >=5 days with MSC, isolated G3; liver transaminase elevation(LTE)/total bilirubin(TBL) that did not downgrade to G1/less in 14 days of onset, isolated G4 LTE/TBL, AST/ALT >3×upper limit normal (ULN) and concurrent TBL >2×ULN, any other toxicity judged by Dose Escalation Committee. The DLT-evaluable population included all participants who received planned doses of study drugs in dose-escalation phase and completed safety follow-up/experienced any DLT during DLT-evaluation period.
    End point type
    Primary
    End point timeframe
    From Day 1 to 28 days after the first dose of study drugs
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    5
    6
    3
    8
    Units: Participants
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase [5] [6]
    End point description
    Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    Notes
    [5] - 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 was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Pyrexia
    3
    3
    0
    1
        Dyspnoea
    1
    0
    0
    0
        Dyspnoea exertional
    0
    1
    0
    0
        Hypotension
    2
    1
    0
    1
        Temperature intolerance
    0
    0
    1
    0
        Hypertension
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase [7] [8]
    End point description
    Number of participants with abnormal ECG parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    Notes
    [7] - 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 was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Atrial fibrillation
    0
    1
    0
    0
        Tachycardia
    0
    1
    0
    0
        Atrioventricular block
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase [9] [10]
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    Notes
    [9] - 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 was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Anaemia
    3
    3
    1
    0
        Neutropenia
    2
    2
    2
    1
        Thrombocytopenia
    2
    2
    2
    1
        Hypothyroidism
    0
    1
    0
    1
        Alanine aminotransferase increased
    3
    4
    0
    2
        Aspartate aminotransferase increased
    3
    3
    0
    3
        Blood alkaline phosphatase increased
    2
    1
    0
    1
        Blood bilirubin increased
    1
    0
    0
    1
        Blood creatinine increased
    0
    3
    0
    0
        Blood glucose decreased
    1
    0
    0
    0
        International normalised ratio increased
    1
    0
    0
    0
        Lymphocyte count decreased
    0
    1
    0
    2
        Neutrophil count decreased
    0
    2
    1
    3
        Platelet count decreased
    1
    3
    1
    2
        White blood cell count decreased
    0
    2
    0
    2
        Hypoalbuminaemia
    0
    2
    0
    1
        Hypocalcaemia
    0
    1
    0
    1
        Hypokalaemia
    0
    3
    0
    2
        Hypomagnesaemia
    1
    2
    0
    1
        Hyponatraemia
    0
    2
    0
    2
        Hypophosphataemia
    0
    1
    0
    0
        Proteinuria
    1
    0
    0
    0
        Hyperthyroidism
    0
    0
    0
    1
        Amylase increased
    0
    0
    1
    1
        Gamma-glutamyltransferase increased
    0
    0
    0
    1
        Lipase increased
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose Expansion Phase [11]
    End point description
    The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), any pathological lymph nodes (LN) (target [TLN] and non-target [NTLN]) must have reduction in short axis <10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. The intent-to treat (ITT) population included all participants who were randomized and received any study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Primary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Percentage of Participants
        number (confidence interval 95%)
    29.0 (18.2 to 41.9)
    21.1 (9.6 to 37.3)
    32.9 (22.1 to 45.1)
    Statistical analysis title
    		 Statistical Analysis 1 (a)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3614 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    -8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.6
         upper limit
    		 12.1
    Notes
    [12] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 2 (a)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6503 [13]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.2
         upper limit
    		 20.7
    Notes
    [13] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 2 (b)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6503 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    3.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 15
    Notes
    [14] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 1 (b)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3614 [15]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    -8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -20.9
         upper limit
    		 5.2
    Notes
    [15] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.

    Secondary: Number of Participants With TEAEs and TESAEs in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With TEAEs and TESAEs in Dose Expansion Phase [16]
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Any TEAEs
    62
    37
    70
        Any TESAEs
    34
    24
    37
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase [17]
    End point description
    Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Hypothermia
    0
    0
    1
        Pyrexia
    15
    12
    21
        Dyspnoea
    7
    6
    8
        Dyspnoea exertional
    1
    1
    2
        Hypertension
    2
    3
    11
        Hypotension
    3
    4
    4
        Orthostatic hypotension
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase [18]
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Anaemia
    17
    14
    28
        Febrile neutropenia
    0
    1
    3
        Leukocytosis
    1
    0
    1
        Leukopenia
    1
    2
    3
        Lymphopenia
    2
    0
    2
        Neutropenia
    22
    15
    16
        Thrombocytopenia
    6
    7
    13
        Thrombocytosis
    2
    0
    1
        Hyperthyroidism
    0
    0
    3
        Hypothyroidism
    0
    0
    7
        Hypertransaminasaemia
    0
    1
    0
        Alanine aminotransferase decreased
    1
    0
    0
        Alanine aminotransferase increased
    8
    9
    16
        Amylase increased
    1
    0
    1
        Aspartate aminotransferase increased
    11
    8
    15
        Blood albumin decreased
    1
    0
    0
        Blood alkaline phosphatase increased
    3
    2
    8
        Blood bilirubin increased
    3
    3
    2
        Blood creatinine increased
    2
    0
    8
        Blood glucose increased
    0
    2
    0
        Blood lactate dehydrogenase increased
    1
    0
    3
        Blood magnesium decreased
    0
    1
    0
        Blood oestrogen decreased
    0
    1
    0
        Gamma-glutamyltransferase increased
    6
    1
    8
        Haemoglobin decreased
    0
    0
    1
        International normalised ratio increased
    0
    0
    1
        Lipase increased
    0
    1
    2
        Liver function test increased
    1
    0
    0
        Lymphocyte count decreased
    4
    2
    6
        Neutrophil count
    0
    0
    1
        Neutrophil count decreased
    19
    8
    24
        Platelet count decreased
    13
    9
    20
        Troponin I increased
    1
    0
    0
        White blood cell count decreased
    6
    6
    10
        White blood cell count increased
    0
    1
    0
        Hyperglycaemia
    4
    2
    6
        Hyperkalaemia
    1
    1
    1
        Hypoalbuminaemia
    3
    2
    6
        Hypocalcaemia
    2
    2
    3
        Hypoglycaemia
    0
    0
    2
        Hypokalaemia
    4
    2
    8
        Hypomagnesaemia
    4
    3
    6
        Hyponatraemia
    8
    0
    3
        Hypophosphataemia
    1
    0
    0
        Hypovolaemia
    1
    0
    0
        Iron deficiency
    0
    0
    1
        Type 2 diabetes mellitus
    0
    1
    0
        Proteinuria
    0
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase [19]
    End point description
    Number of participants with abnormal ECG parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Supraventricular tachycardia
    0
    1
    0
        Tachycardia
    2
    3
    3
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase [20]
    End point description
    DC: defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis <10 mm, and no new lesions. The PR is at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from first documentation date. The SD is neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for progressive disease (PD), and no new lesions. The PD is at least 20% increase in SoD of TLs and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Percentage of Participants
        number (confidence interval 95%)
    42.9 (9.9 to 81.6)
    71.4 (29.0 to 96.3)
    66.7 (9.4 to 99.2)
    62.5 (24.5 to 91.5)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase

    		 Close Top of page
    End point title
    		 Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase [21]
    End point description
    The OR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. The numbers of confidence interval (CI) '0 to 0' signified that there was zero responder in the specified cohort, so 95% CI could not be calculated.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Percentage of Participants
        number (confidence interval 95%)
    0 (0 to 0)
    14.3 (0.4 to 57.9)
    0 (0 to 0)
    12.5 (0.3 to 52.7)
    No statistical analyses for this end point

    Secondary: Number of Participants With Overall Survival Events in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Overall Survival Events in Dose Expansion Phase [22]
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. The number of participants with overall survival events (deaths) is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants with event
        number (not applicable)
    47
    32
    53
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.498
         upper limit
    		 1.131
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.983

    Secondary: Number of Participants With Progression-free Survival (PFS) Events According to RECIST v1.1 in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Progression-free Survival (PFS) Events According to RECIST v1.1 in Dose Expansion Phase [23]
    End point description
    The PFS is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. PD: at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. The number of participants with PFS events is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants with event
        number (not applicable)
    43
    32
    51
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.719
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.468
         upper limit
    		 1.105
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.726
         upper limit
    		 1.837

    Secondary: Overall Survival in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Overall Survival in Dose Expansion Phase [24]
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Months
        median (confidence interval 95%)
    10.8 (8.2 to 13.2)
    8.9 (6.9 to 11.5)
    12.9 (10.1 to 15.3)
    No statistical analyses for this end point

    Secondary: Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase [25]
    End point description
    Progression-free survival (PFS) is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. The PD is defined as at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Months
        median (confidence interval 95%)
    6.7 (5.5 to 9.0)
    5.6 (3.5 to 7.5)
    7.5 (5.5 to 10.9)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase [26]
    End point description
    DoR: Time from first documentation of OR until first documentation of PD/death due to any cause, whichever occurred first. OR: Confirmed CR/PR based on RECIST v1.1. CR: Disappearance of all TLs and NTLs, any pathological TLN and NTLN must had reduction in short axis <10 mm and no new lesions. PR: At least 30% decrease in SoD of TLs and no new lesions. Confirmation of CR and PR is required by repeat,consecutive assessment no less than 4 weeks from first documentation date. PD: At least 20% increase in SoD of TLs and absolute increase of at least 5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion/s. DoR is assessed using Kaplan-Meier method. ITT population included all participants who received any study drugs and analyzed according to randomized treatment assignment. DoR is assessed for only those participants who had OR. The arbitrary number 99.99 signified upper limit confidence interval (CI) could not be derived due to insufficient events being observed.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    18
    8
    23
    Units: Months
        median (confidence interval 95%)
    7.2 (4.9 to 99.99)
    12.9 (2.2 to 99.99)
    9.5 (5.7 to 12.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase [27]
    End point description
    DC: defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis <10 mm, and no new lesions. The PR is at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from first documentation date. The SD is neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for PD, and no new lesions. The PD is at least 20% increase in SoD of TLs and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. The ITT population included all participants who were randomized and received any study drugs and analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Percentage of Participants
        number (confidence interval 95%)
    66.1 (53.0 to 77.7)
    73.7 (56.9 to 86.6)
    75.7 (64.0 to 85.2)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    OR: Best overall response of confirmed CR/PR based on RECIST v1.1. CR: Disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must had reduction in short axis <10 mm, and no new lesions. PR: At least 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than weeks from first documentation date. The OR is assessed by cluster of differentiation 73 (CD73) expression level either low or high at baseline. CD73 low: No CD73 expression in tumor cells or <50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Percentage of Participants
        number (confidence interval 95%)
    23.9 (12.6 to 38.8)
    22.2 (8.6 to 42.3)
    31.4 (19.1 to 45.9)
    43.8 (19.8 to 70.1)
    18.2 (2.3 to 51.8)
    36.8 (16.3 to 61.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.2
         upper limit
    		 21.9
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -25.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.3
         upper limit
    		 13.9
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.1
         upper limit
    		 26.6
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.6
         upper limit
    		 27

    Secondary: Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. The number of participants with overall survival events (deaths) is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Participants with events
        number (not applicable)
    37
    22
    39
    10
    10
    14
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.676
         upper limit
    		 1.985
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.472
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.638
         upper limit
    		 3.576
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.549
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.622
         upper limit
    		 3.917
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.605
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.377
         upper limit
    		 0.968

    Secondary: Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Months
        median (confidence interval 95%)
    9.9 (6.8 to 12.2)
    7.9 (4.2 to 9.7)
    12.1 (8.6 to 15.0)
    22.2 (10.2 to 33.6)
    16.0 (5.7 to 22.6)
    16.1 (10.3 to 21.0)
    No statistical analyses for this end point

    Secondary: Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    PFS: Time from randomization until first documentation of PD/death due to any cause, whichever occurred first, regardless of whether participant received subsequent anticancer treatment prior to progression. PD:>=20% increase in SoD of TLs and an absolute increase of >= 5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion. Participants who had no documented progression and were still alive at the time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. Number of participants with PFS events is reported. ITT population was analyzed for this endpoint. "Number of subjects analyzed" (N) signified those participants who had high/low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Participants with event
        number (not applicable)
    35
    23
    39
    8
    9
    12
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.598
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.366
         upper limit
    		 0.973
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.584
         upper limit
    		 1.693
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.374
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 3.707
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.933
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.716
         upper limit
    		 5.437

    Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab

    		 Close Top of page
    End point title
    		 Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab [28]
    End point description
    Number of participants with positive ADA to oleclumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. The ADA evaluable oleclumab population included all participants who received oleclumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (Pre-dose on Cycle [C] 1 Day [D] 1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of oleclumab)
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    6
    7
    3
    7
    31
    63
    Units: Participants
        ADA positive at baseline
    0
    0
    0
    0
    0
    0
        ADA positive post-baseline
    1
    0
    0
    1
    1
    0
        Persistent Positive
    1
    0
    0
    1
    0
    0
        Transient Positive
    0
    0
    0
    0
    1
    0
        Treatment-boosted ADA
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

    		 Close Top of page
    End point title
    		 Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    PFS:Time from randomization until first documentation of PD/death due to any cause, whichever occurred first, regardless of subsequent anticancer treatment prior to progression. PD:>=20% increase in SoD of TLs and absolute increase of >=5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion. Participants who had no documented progression and were still alive at time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. ITT population was analyzed for this endpoint. "Number of subjects analyzed"(N) signified those participants who had high/low levels of CD73. Arbitrary number 99.99 signified upper limit CI could not be derived due to insufficient events.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Months
        median (confidence interval 95%)
    5.6 (3.7 to 7.4)
    5.2 (1.9 to 6.3)
    5.5 (4.4 to 9.3)
    10.5 (6.9 to 99.99)
    7.6 (3.3 to 11.2)
    10.9 (5.7 to 13.2)
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive ADA to Durvalumab

    		 Close Top of page
    End point title
    		 Number of Participants With Positive ADA to Durvalumab [29]
    End point description
    Number of participants with positive ADA to durvalumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. The ADA evaluable durvalumab population included all participants who received durvalumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
    End point type
    Secondary
    End point timeframe
    Day 1 through 128 weeks (Pre-dose on C1D1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of durvalumab)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    6
    7
    3
    7
    60
    Units: Participants
        ADA positive at baseline
    0
    0
    0
    0
    2
        ADA positive post-baseline
    1
    0
    0
    2
    0
        Persistent Positive
    1
    0
    0
    2
    0
        Transient Positive
    0
    0
    0
    0
    0
        Treatment-boosted ADA
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Oleclumab

    		 Close Top of page
    End point title
    		 Serum Concentrations of Oleclumab [30]
    End point description
    Serum concentrations of oleclumab are reported. Pharmacokinetic (PK) evaluable oleclumab population included all participants who received at least one dose of oleclumab and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm. The arbitrary numbers 999.99 and 9999.9 signified that the geometric mean and geometric CV% could not be calculated as no participant was analysed at that time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten minutes (mins) (± 5 mins) post end of infusion (EOI), approximately 1 hour (+ 15 mins) after start of infusion on C1D1, C3D1, and C5D1; and pre-dose on C3D1 and C5D1
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    3
    8
    38
    70
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,3,7,37,70)
    297.6 ( 25.70 )
    710.2 ( 21.42 )
    412.7 ( 11.12 )
    734.6 ( 41.01 )
    704.4 ( 30.28 )
    725.9 ( 34.69 )
        C3D1 (pre-dose) (n=3,5,3,4,27,57)
    128.6 ( 10.00 )
    211.5 ( 73.40 )
    134.3 ( 141.5 )
    368.9 ( 2.461 )
    164.8 ( 324.1 )
    226.8 ( 70.41 )
        C3D1 (EOI) (n=2,5,3,4,25,57)
    0.99999 ( 99999 )
    870.3 ( 21.86 )
    571.1 ( 15.75 )
    1181 ( 24.97 )
    893.0 ( 30.66 )
    894.4 ( 39.22 )
        C5D1 (pre-dose) (n=1,3,0,4,20,45)
    0.99999 ( 99999 )
    73.19 ( 130.2 )
    999.99 ( 9999.9 )
    235.7 ( 27.68 )
    85.99 ( 192.0 )
    116.4 ( 54.0 )
        C5D1 (EOI) (n=1,3,0,4,20,45)
    0.99999 ( 99999 )
    948.3 ( 44.90 )
    999.99 ( 9999.9 )
    1057 ( 14.88 )
    852.8 ( 24.77 )
    753.2 ( 41.32 )
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Durvalumab

    		 Close Top of page
    End point title
    		 Serum Concentrations of Durvalumab [31]
    End point description
    Serum concentrations of durvalumab are reported. The PK evaluable durvalumab population included all participants who received at least one dose of durvalumab and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm. The arbitrary numbers 999.99 and 9999.9 signified that the geometric mean and geometric CV% could not be calculated as no participant was analysed at that time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 1 hour (+ 15 mins) after start of infusion on C1D1 and C5D1; and pre-dose on C2D1 and C5D1
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    3
    8
    70
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,3,8,70)
    292.5 ( 11.72 )
    374.5 ( 27.50 )
    309.0 ( 11.58 )
    380.7 ( 56.89 )
    345.8 ( 324.2 )
        C2D1 (pre-dose) (n=5,6,3,7,61)
    35.97 ( 51.44 )
    14.39 ( 5129 )
    50.52 ( 57.30 )
    59.97 ( 176.7 )
    86.20 ( 97.95 )
        C5D1 (pre-dose) (n=1,3,0,4,45)
    0.99999 ( 99999 )
    74.52 ( 28.32 )
    999.99 ( 9999.9 )
    175.9 ( 43.50 )
    137.9 ( 48.85 )
        C5D1 (EOI) (n=1,3,0,4,44)
    0.99999 ( 99999 )
    522.1 ( 46.72 )
    999.99 ( 9999.9 )
    664.5 ( 28.14 )
    597.9 ( 23.40 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Gemcitabine and Metabolite 2’,2’-Difluorodeoxyuridine (dFdU)

    		 Close Top of page
    End point title
    		 Plasma Concentrations of Gemcitabine and Metabolite 2’,2’-Difluorodeoxyuridine (dFdU) [32]
    End point description
    Plasma concentrations of gemcitabine and metabolite dFdU are reported. The PK evaluable gemcitabine population included all participants who received at least one dose of gemcitabine and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    57
    38
    70
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Gemcitabine C1D1 (EOI) (n=7,7,54,36,65)
    3194 ( 64.74 )
    4659 ( 67.41 )
    3301 ( 192.0 )
    3315 ( 135.4 )
    4086 ( 148.9 )
        Gemcitabine C4D1 (pre-dose) (n=2,4,33,25,50)
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
        Gemcitabine C4D1 (EOI) (n=2,4,28,25,49)
    0.99999 ( 99999 )
    3530 ( 48.11 )
    1748 ( 236.5 )
    1431 ( 446.3 )
    2998 ( 151.3 )
        dFdU C1D1 (EOI) (n=7,7,54,36,65)
    33700 ( 14.70 )
    32160 ( 17.67 )
    29510 ( 113.4 )
    32350 ( 17.10 )
    26300 ( 163.9 )
        dFdU C4D1 (pre-dose) (n=2,4,33,25,50)
    0.99999 ( 99999 )
    434.6 ( 344.7 )
    245.1 ( 361.5 )
    149.9 ( 147.0 )
    177.5 ( 170.0 )
        dFdU C4D1 (EOI) (n=2,4,28,25,49)
    0.99999 ( 99999 )
    34550 ( 35.37 )
    23900 ( 189.1 )
    21970 ( 130.3 )
    27260 ( 43.07 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Nab-paclitaxel

    		 Close Top of page
    End point title
    		 Plasma Concentrations of Nab-paclitaxel [33]
    End point description
    Plasma concentrations of nab-paclitaxel are reported. The PK evaluable nab-paclitaxel population included all participants who received at least one dose of nab-paclitaxel and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    60
    38
    70
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,58,35,69)
    1711 ( 80.37 )
    2685 ( 63.55 )
    2381 ( 105.2 )
    2711 ( 81.67 )
    2611 ( 142.0 )
        C4D1 (pre-dose) (n=2,4,35,24,47)
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
        C4D1 (EOI) (n=2,4,31,24,48)
    0.99999 ( 99999 )
    1474 ( 96.12 )
    1825 ( 178.1 )
    1445 ( 145.8 )
    1747 ( 99.26 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through 172.1 weeks (maximum observed duration)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Serious adverse events
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 7 (57.14%)
    6 / 7 (85.71%)
    0 / 3 (0.00%)
    4 / 8 (50.00%)
    34 / 62 (54.84%)
    24 / 38 (63.16%)
    37 / 70 (52.86%)
         number of deaths (all causes)
    7
    7
    3
    8
    47
    32
    53
         number of deaths resulting from adverse events
    1
    0
    0
    0
    3
    1
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Shock
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Localised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    3 / 38 (7.89%)
    8 / 70 (11.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    3 / 6
    3 / 3
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    4 / 70 (5.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemolytic uraemic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    4 / 62 (6.45%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    2 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    5 / 62 (8.06%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 1
    3 / 5
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder rupture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bullous impetigo
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Hepatic infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    60 / 62 (96.77%)
    36 / 38 (94.74%)
    70 / 70 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cancer fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cryoglobulinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Deep vein thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    0
    0
    5
    3
    1
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Flushing
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    3 / 38 (7.89%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    3
    Orthostatic hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    3 / 38 (7.89%)
    10 / 70 (14.29%)
         occurrences all number
    0
    0
    0
    1
    2
    7
    15
    Hypotension
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    4 / 38 (10.53%)
    4 / 70 (5.71%)
         occurrences all number
    2
    1
    0
    1
    3
    4
    4
    Haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Phlebitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Superficial vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Asthenia
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    8 / 62 (12.90%)
    4 / 38 (10.53%)
    7 / 70 (10.00%)
         occurrences all number
    2
    2
    0
    0
    9
    9
    10
    Catheter site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    6 / 38 (15.79%)
    9 / 70 (12.86%)
         occurrences all number
    0
    0
    0
    0
    3
    11
    10
    Early satiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    6 / 7 (85.71%)
    7 / 7 (100.00%)
    2 / 3 (66.67%)
    6 / 8 (75.00%)
    30 / 62 (48.39%)
    25 / 38 (65.79%)
    41 / 70 (58.57%)
         occurrences all number
    6
    9
    2
    7
    33
    60
    54
    Feeling abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gait disturbance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Generalised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Hypothermia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Localised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    Influenza like illness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    7 / 70 (10.00%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    10
    Infusion site extravasation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Injection site reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Illness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    13 / 62 (20.97%)
    12 / 38 (31.58%)
    28 / 70 (40.00%)
         occurrences all number
    4
    4
    0
    2
    15
    21
    41
    Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    2
    0
    0
    1
    1
    2
    1
    Peripheral swelling
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    2
    0
    0
    0
    1
    2
    1
    Pyrexia
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    10 / 62 (16.13%)
    10 / 38 (26.32%)
    18 / 70 (25.71%)
         occurrences all number
    4
    2
    0
    1
    14
    16
    26
    Temperature intolerance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    3 / 38 (7.89%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    1
    1
    3
    3
    3
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    1
    0
    0
    2
    3
    1
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    Unevaluable event
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Immunisation reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Pelvic discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Prostatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    2
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    4 / 38 (10.53%)
    11 / 70 (15.71%)
         occurrences all number
    1
    2
    0
    0
    6
    5
    13
    Dysphonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    6 / 62 (9.68%)
    6 / 38 (15.79%)
    7 / 70 (10.00%)
         occurrences all number
    1
    0
    0
    0
    7
    6
    7
    Bronchiectasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    5 / 70 (7.14%)
         occurrences all number
    2
    0
    0
    0
    3
    2
    6
    Hiccups
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    1
    3
    2
    1
    Hypoxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Nasal congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    4
    Pulmonary congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    3
    Orthopnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    4
    Pneumonitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    1
    0
    0
    0
    1
    2
    4
    Nasal ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    2 / 38 (5.26%)
    4 / 70 (5.71%)
         occurrences all number
    1
    0
    0
    0
    4
    2
    4
    Pulmonary oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    0
    0
    Throat irritation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Sinus congestion
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    Psychiatric disorders
    Depressive symptom
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Agitation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    4 / 38 (10.53%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    1
    3
    4
    2
    Confusional state
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    2
    Depression
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    5 / 70 (7.14%)
         occurrences all number
    1
    1
    0
    0
    2
    1
    5
    Disorientation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    5 / 38 (13.16%)
    7 / 70 (10.00%)
         occurrences all number
    2
    0
    0
    1
    3
    9
    7
    Mania
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Mental status changes
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Persistent depressive disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    11 / 62 (17.74%)
    8 / 38 (21.05%)
    15 / 70 (21.43%)
         occurrences all number
    3
    6
    0
    3
    14
    9
    22
    Alanine aminotransferase decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Amylase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 7 (42.86%)
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    8 / 62 (12.90%)
    9 / 38 (23.68%)
    16 / 70 (22.86%)
         occurrences all number
    3
    4
    0
    2
    9
    10
    22
    Blood bilirubin increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    3 / 38 (7.89%)
    2 / 70 (2.86%)
         occurrences all number
    1
    0
    0
    1
    3
    3
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    8 / 70 (11.43%)
         occurrences all number
    2
    3
    0
    1
    3
    2
    9
    Blood albumin decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    Lipase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    2
    Liver function test increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    6 / 62 (9.68%)
    1 / 38 (2.63%)
    8 / 70 (11.43%)
         occurrences all number
    0
    0
    0
    2
    8
    1
    10
    Blood oestrogen decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blood magnesium decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    3
    Blood glucose decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    8 / 70 (11.43%)
         occurrences all number
    0
    3
    0
    0
    2
    0
    10
    Blood glucose increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Weight increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    Weight decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    4 / 62 (6.45%)
    7 / 38 (18.42%)
    7 / 70 (10.00%)
         occurrences all number
    0
    0
    1
    1
    4
    7
    8
    White blood cell count increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    6 / 62 (9.68%)
    6 / 38 (15.79%)
    10 / 70 (14.29%)
         occurrences all number
    0
    4
    0
    2
    19
    8
    19
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    4 / 62 (6.45%)
    2 / 38 (5.26%)
    6 / 70 (8.57%)
         occurrences all number
    0
    2
    0
    3
    11
    2
    8
    Neutrophil count
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    3 / 8 (37.50%)
    19 / 62 (30.65%)
    8 / 38 (21.05%)
    24 / 70 (34.29%)
         occurrences all number
    0
    3
    2
    4
    41
    13
    49
    Platelet count decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    13 / 62 (20.97%)
    9 / 38 (23.68%)
    20 / 70 (28.57%)
         occurrences all number
    2
    6
    2
    3
    39
    24
    50
    Urine output decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Troponin I increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Contusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Fall
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    5 / 70 (7.14%)
         occurrences all number
    1
    0
    0
    0
    5
    2
    7
    Foot fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    4
    Limb injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Procedural complication
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rib fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Skin abrasion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Skin laceration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    Spinal compression fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Thermal burn
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Wound
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Atrioventricular block
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Angina pectoris
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    3 / 38 (7.89%)
    3 / 70 (4.29%)
         occurrences all number
    0
    1
    0
    0
    2
    3
    4
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Akathisia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Ageusia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Burning sensation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    6 / 62 (9.68%)
    7 / 38 (18.42%)
    6 / 70 (8.57%)
         occurrences all number
    0
    0
    0
    1
    7
    7
    9
    Disturbance in attention
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Cerebral ischaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Hypersomnia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Headache
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    6 / 62 (9.68%)
    3 / 38 (7.89%)
    12 / 70 (17.14%)
         occurrences all number
    0
    2
    0
    1
    6
    3
    13
    Dysgeusia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 7 (42.86%)
    2 / 3 (66.67%)
    0 / 8 (0.00%)
    10 / 62 (16.13%)
    5 / 38 (13.16%)
    12 / 70 (17.14%)
         occurrences all number
    0
    3
    2
    0
    10
    10
    13
    Memory impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Neuralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    11 / 62 (17.74%)
    11 / 38 (28.95%)
    13 / 70 (18.57%)
         occurrences all number
    5
    1
    0
    2
    13
    12
    17
    Polyneuropathy in malignant disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    9 / 62 (14.52%)
    11 / 38 (28.95%)
    15 / 70 (21.43%)
         occurrences all number
    0
    3
    0
    1
    11
    17
    17
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Neurotoxicity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    4
    1
    1
    Presyncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Restless legs syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Taste disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    2 / 70 (2.86%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    2
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    22 / 62 (35.48%)
    14 / 38 (36.84%)
    16 / 70 (22.86%)
         occurrences all number
    2
    13
    3
    1
    37
    25
    36
    Lymphopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    2
    Lymphadenopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    8
    Leukocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Splenic infarction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Febrile neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Anaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    17 / 62 (27.42%)
    14 / 38 (36.84%)
    27 / 70 (38.57%)
         occurrences all number
    4
    4
    2
    0
    25
    15
    41
    Haemolytic uraemic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Thrombocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    6 / 62 (9.68%)
    7 / 38 (18.42%)
    13 / 70 (18.57%)
         occurrences all number
    5
    3
    3
    1
    8
    10
    24
    Splenic vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Ear congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    2
    Hypoacusis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Meniere's disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cataract
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Dry eye
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hypermetropia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye irritation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Eyelid irritation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Eyelid ptosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Glaucoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye allergy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Orbital haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Periorbital pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Photopsia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    4
    Visual field defect
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vitreous floaters
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Ocular hyperaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    12 / 62 (19.35%)
    6 / 38 (15.79%)
    13 / 70 (18.57%)
         occurrences all number
    2
    3
    2
    1
    13
    7
    16
    Abdominal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Abdominal distension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    2
    2
    2
    3
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    5 / 62 (8.06%)
    4 / 38 (10.53%)
    5 / 70 (7.14%)
         occurrences all number
    0
    1
    0
    1
    5
    4
    5
    Abdominal tenderness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Anal incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Anorectal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    3 / 38 (7.89%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    1
    2
    3
    3
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Constipation
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 7 (71.43%)
    2 / 3 (66.67%)
    2 / 8 (25.00%)
    10 / 62 (16.13%)
    15 / 38 (39.47%)
    18 / 70 (25.71%)
         occurrences all number
    2
    5
    2
    2
    13
    21
    28
    Diarrhoea
         subjects affected / exposed
    5 / 7 (71.43%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    5 / 8 (62.50%)
    18 / 62 (29.03%)
    14 / 38 (36.84%)
    36 / 70 (51.43%)
         occurrences all number
    6
    2
    1
    6
    26
    29
    63
    Dry mouth
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    0
    3
    2
    4
    Dyspepsia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    4 / 38 (10.53%)
    7 / 70 (10.00%)
         occurrences all number
    0
    1
    0
    0
    2
    4
    7
    Colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Faeces discoloured
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Flatulence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    2
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Gingival pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    3
    0
    0
    0
    1
    1
    2
    Mouth ulceration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Nausea
         subjects affected / exposed
    6 / 7 (85.71%)
    6 / 7 (85.71%)
    2 / 3 (66.67%)
    4 / 8 (50.00%)
    26 / 62 (41.94%)
    26 / 38 (68.42%)
    41 / 70 (58.57%)
         occurrences all number
    6
    8
    2
    5
    34
    70
    49
    Odynophagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oedema mouth
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Melaena
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Periodontal disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Proctitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Oral dysaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    5 / 62 (8.06%)
    3 / 38 (7.89%)
    7 / 70 (10.00%)
         occurrences all number
    0
    0
    0
    3
    5
    5
    7
    Tongue blistering
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Vomiting
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    3 / 8 (37.50%)
    15 / 62 (24.19%)
    12 / 38 (31.58%)
    16 / 70 (22.86%)
         occurrences all number
    4
    2
    1
    3
    21
    18
    23
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Cholangitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Congestive hepatopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hepatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    4 / 70 (5.71%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    6
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Portal vein occlusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Portal vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Haemorrhagic hepatic cyst
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Eczema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dermal cyst
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Dermatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    4 / 38 (10.53%)
    3 / 70 (4.29%)
         occurrences all number
    1
    0
    0
    0
    0
    4
    5
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    5 / 38 (13.16%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    2
    5
    3
    Alopecia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    12 / 62 (19.35%)
    11 / 38 (28.95%)
    25 / 70 (35.71%)
         occurrences all number
    1
    3
    0
    0
    12
    11
    26
    Erythema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    0
    Hair colour changes
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    5
    1
    Nail discolouration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Night sweats
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    2
    Onychalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Onycholysis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Onychomadesis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Pain of skin
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Petechiae
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    5 / 62 (8.06%)
    6 / 38 (15.79%)
    16 / 70 (22.86%)
         occurrences all number
    1
    1
    0
    1
    5
    10
    18
    Purpura
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    4 / 62 (6.45%)
    6 / 38 (15.79%)
    13 / 70 (18.57%)
         occurrences all number
    1
    1
    0
    1
    4
    15
    14
    Rash erythematous
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Rash macular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Skin fissures
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Rash papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rash pruritic
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    1
    Skin discolouration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Skin exfoliation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    6 / 38 (15.79%)
    12 / 70 (17.14%)
         occurrences all number
    0
    0
    0
    0
    5
    17
    19
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    Skin ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Urticaria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Vitiligo
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    4
    Renal failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Micturition urgency
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Nephrolithiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    1
    Dysuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    3
    0
    0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Urinary retention
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    Urinary tract pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    3
    Hypothyroidism
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    7 / 70 (10.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    7
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    8 / 62 (12.90%)
    7 / 38 (18.42%)
    10 / 70 (14.29%)
         occurrences all number
    2
    2
    2
    1
    10
    9
    14
    Muscle spasms
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 62 (0.00%)
    4 / 38 (10.53%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    2
    0
    7
    2
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    4
    1
    0
    Flank pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    Joint swelling
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Limb discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    3 / 38 (7.89%)
    10 / 70 (14.29%)
         occurrences all number
    0
    1
    0
    0
    1
    3
    10
    Muscle tightness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    8 / 62 (12.90%)
    4 / 38 (10.53%)
    8 / 70 (11.43%)
         occurrences all number
    2
    0
    0
    0
    8
    4
    8
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    4 / 70 (5.71%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    5
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Synovial cyst
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Myopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Myositis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    4 / 38 (10.53%)
    10 / 70 (14.29%)
         occurrences all number
    0
    1
    0
    0
    3
    6
    10
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    8 / 38 (21.05%)
    14 / 70 (20.00%)
         occurrences all number
    0
    0
    1
    0
    3
    10
    19
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    Abdominal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Candida infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    2
    Catheter site infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Diverticulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    External ear cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Herpes simplex
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Liver abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rash pustular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Mucosal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    3
    Oesophageal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    Otitis media
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Paronychia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Sputum purulent
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    1
    0
    0
    1
    2
    3
    6
    Vaginal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 7 (57.14%)
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    3 / 8 (37.50%)
    16 / 62 (25.81%)
    15 / 38 (39.47%)
    21 / 70 (30.00%)
         occurrences all number
    4
    3
    1
    3
    17
    58
    22
    Dehydration
         subjects affected / exposed
    4 / 7 (57.14%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    6 / 62 (9.68%)
    1 / 38 (2.63%)
    10 / 70 (14.29%)
         occurrences all number
    4
    2
    1
    2
    6
    1
    12
    Gout
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    4 / 62 (6.45%)
    2 / 38 (5.26%)
    8 / 70 (11.43%)
         occurrences all number
    0
    5
    0
    3
    9
    3
    12
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    6 / 70 (8.57%)
         occurrences all number
    0
    2
    0
    1
    3
    2
    7
    Hypocalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    2 / 38 (5.26%)
    3 / 70 (4.29%)
         occurrences all number
    0
    4
    0
    1
    3
    2
    4
    Hypoglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Hyperglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    2 / 38 (5.26%)
    6 / 70 (8.57%)
         occurrences all number
    0
    0
    0
    0
    5
    2
    9
    Hypomagnesaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    4 / 62 (6.45%)
    3 / 38 (7.89%)
    6 / 70 (8.57%)
         occurrences all number
    1
    4
    0
    1
    8
    3
    9
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    8 / 62 (12.90%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    4
    0
    3
    9
    0
    2
    Hypophosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    Hypovolaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Iron deficiency
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Jun 2019
    Section 3.1.1 (Overview), Figure 2 (3.1.1-2) (Study Flow Diagram [Part 2: Dose Expansion]), Sections 4.1.1 (Number of Subjects), 4.8.2 (Sample Size), and 4.8.7 (Interim Analysis): Revised Part 2 of the study design as detailed next. Cohort A Part 2: Revised number of participants to include an additional 30 participants per treatment arm (now up to 60 participants per treatment arm). Revised significance level to 0.10 (previously 0.15) and increased power to 77% (previously 66%) in Section 4.8.2. Added an interim analysis in Section 4.8.7 when approximately 30 evaluable participants in each treatment arm have been dosed and reach the data cut off criteria. Cohort B Part 2: Revised the sample size to 35 participants per treatment arm. Revised significance level to 0.10 (previously 0.15), revised difference in OR rate to 20% (previously 15%), and increased power to 72% (previously 63%) in Section 4.8.2. Updated total number of participants. Section 3.1.3.4 (Safety Review Committee [SRC]): Added SRC to provide details regarding ongoing safety surveillance of participants during the randomization phase of the study. Section 4.1.2 (Inclusion Criteria): For Criterion 8, Table 5 (4.1.2-1) (Criteria for Adequate Organ and Marrow Function), clarified that TBL =<3 × ULN in presence of documented Gilbert’s syndrome or liver metastases is allowed only for participants in Cohort B. Section 4.1.3 (Exclusion Criteria): Revised as- Criterion 5: Clarified that participants with thrombosis due to mechanical obstruction by the tumor that is found incidentally and is asymptomatic and does not require therapy may be enrolled at the investigator’s discretion and should be monitored closely. Criterion 21: Added exclusion criterion for participants with known allergy or hypersensitivity to gemcitabine, nab-paclitaxel, oxaliplatin, folinic acid, or 5-FU. Section 4.7.2 (Prohibited Concomitant Medications): Added cannabinoids as prohibited concomitant medication for oleclumab treatment arms.
    20 Dec 2019
    Section 1.6.1 (Potential Risks): Revised arterial calcifications and arterial ischemic disorder to potential risks for oleclumab. Revised risks for durvalumab. Sections 3.1.1 (Overview), 4.1.1 (Number of Subjects), 4.8.2 (Sample Size), and Figure 2 (3.1.1-2; Study Flow Diagram [Part 2: Dose Expansion]): Revised to reflect a sample size of 70 participants per treatment arm for Cohort A (Part 2 [Dose Expansion]). Section 3.1.4.1 and 10.9 (previously numbered 10.10): Revised toxicity management guidelines in Section 10.9. Section 3.1.4.2: Added new section with information regarding toxicity management guidelines for durvalumab. Section 4.1.7: Added statement in the second paragraph that participants with unconfirmed radiologic PD who were eligible to continue receiving their assigned treatment were to be made aware of the potential benefits and risks of continuing treatment in the setting of PD and must provide a separate written informed consent prior to treatment. Section 4.2.3 (Follow-up Period): Added assessment for pregnancy testing Q4W starting 8 weeks through 28 weeks post last dose during follow up in Table 9 (4.2.3-1; Schedule of Follow-up Procedures [Part 1 (Dose Escalation) and Part 2 (Dose Expansion)]). The frequency of the pregnancy testing was updated to align with contraception requirements in the inclusion criteria and the Summary of Product Characteristics for the chemotherapy drugs. Sections 4.5.1.2 (Oleclumab [MEDI9447] IV Bag Preparation and Administration) and 4.5.1.3 (Durvalumab [MEDI4736] IV Bag Preparation and Administration): Revised to require that participant weight was > 30 kg for fixed dosing of oleclumab and durvalumab due to endotoxin levels. Section 5.3.3 (Adverse Events of Special Interest [AESI] for Durvalumab): Added AESIs of vasculitis, non-infectious meningitis, and non-infectious encephalitis per durvalumab IB edition 15.0.
    24 Jun 2022
    Section 4.4.1 (Continued Treatment at Study Completion): New section added to describe the continued treatment period for participants still receiving investigational product at the time of data entry cut off. Sections 1.6.1 (Potential Risks) and 5.3.2.1 (Cardiac Chest Pain, Transient Ischemic Attack, and Thromboembolism): The known and potential risks for oleclumab and durvalumab were updated in line with the most recent information.

    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.
    Dose escalation phase: Participants not enrolled in oleclumab 750 mg cohort. Dose expansion phase: Outcomes of mFOLFOX cohorts not included as enrollment was not opened. Non-compartmental PK parameters were not calculated due to sparse PK samples.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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.

    European Medicines Agency © 1995-Fri May 03 12:12:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA