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    Clinical Trial Results:
    A Phase Ib/II Study Evaluating the Safety and Efficacy of Idasanutlin in Combination with Cytarabine and Daunorubicin in Patients Newly Diagnosed with Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission

    Summary
    EudraCT number
    		 2018-002964-25
    Trial protocol
    		 FR   ES   IT  
    Global end of trial date
    10 Aug 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Sep 2021
    First version publication date
    19 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GO40800
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, +41
    Public contact
    Roche Trial Information Hotline, Roche Trial Information Hotline, +41 61 6878333,
    Scientific contact
    Medical Communications, Hoffmann-La Roche, CH-4070 800 8218590, genentech@druginfo.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
    24 Feb 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Aug 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    A Study Evaluating the Safety and Efficacy of Idasanutlin in Combination with Cytarabine and Daunorubicin in Patients Newly Diagnosed with Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) guidelines according to the regulations and procedures described in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Mar 2019
    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: 4
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    United States: 17
    Worldwide total number of subjects
    23
    EEA total number of subjects
    2
    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)
    18
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 24 subjects were enrolled from total of 40 subjects

    Pre-assignment
    Screening details
    		 A total of 40 patients were screened; 17 patients failed the screening and 23 patients were enrolled and treated from 11 centers from the following four countries including the USA (7 Centers), Australia (2 centers), France (1 Center), and Italy (1 Center)

    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 Cohort 1
    Arm description
    		 For maintenance, participants were treated with single agent idasanutlin of 150mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction

    Arm title
    		 Dose Escalation Cohort 2
    Arm description
    		 350mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    350mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction

    Arm title
    		 Dose Escalation Cohort 3
    Arm description
    		 For induction, participants will be treated with 250mg idasanultin plus cytarabine. For maintenance, participants will be treated with single agent idasanutlin of 150 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    250mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction

    Arm title
    		 Post Consolidation Cohort
    Arm description
    		 Post consolidation cohort (experimental). 150mg idasanultin day 1 to 5 in maintenance of first remission
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idasnutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150mg idasanultin day 1 to 5 in maintenance of first remission

    Number of subjects in period 1
    		Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Started
    4
    9
    6
    4
    Completed
    0
    0
    0
    0
    Not completed
    4
    9
    6
    4
         Sponsor's decision to terminate
    4
    9
    6
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dose-Escalation Cohort 1
    Reporting group description
    		 For maintenance, participants were treated with single agent idasanutlin of 150mg

    Reporting group title
    Dose Escalation Cohort 2
    Reporting group description
    		 350mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction

    Reporting group title
    Dose Escalation Cohort 3
    Reporting group description
    		 For induction, participants will be treated with 250mg idasanultin plus cytarabine. For maintenance, participants will be treated with single agent idasanutlin of 150 mg

    Reporting group title
    Post Consolidation Cohort
    Reporting group description
    		 Post consolidation cohort (experimental). 150mg idasanultin day 1 to 5 in maintenance of first remission

    Reporting group values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort Total
    Number of subjects
    		 4 9 6 4 23
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 3 7 6 2 18
        From 65-84 years
    		 1 2 0 2 5
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 49.5 ( 17.1 ) 45.2 ( 16.9 ) 49.8 ( 14.0 ) 64.8 ( 7.2 ) -
    Sex: Female, Male
    Units:
        Female
    		 2 3 3 3 11
        Male
    		 2 6 3 1 12
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 1 0 0 1
        White
    		 3 7 4 3 17
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 1 1 2 1 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 0 5 0 6
        Not Hispanic or Latino
    		 2 9 0 3 14
        Unknown or Not Reported
    		 1 0 1 1 3

    End points

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    End points reporting groups
    Reporting group title
    Dose-Escalation Cohort 1
    Reporting group description
    		 For maintenance, participants were treated with single agent idasanutlin of 150mg

    Reporting group title
    Dose Escalation Cohort 2
    Reporting group description
    		 350mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction

    Reporting group title
    Dose Escalation Cohort 3
    Reporting group description
    		 For induction, participants will be treated with 250mg idasanultin plus cytarabine. For maintenance, participants will be treated with single agent idasanutlin of 150 mg

    Reporting group title
    Post Consolidation Cohort
    Reporting group description
    		 Post consolidation cohort (experimental). 150mg idasanultin day 1 to 5 in maintenance of first remission

    Primary: Dose Escalation Phase: Number of Participants with Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment

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    End point title
    		 Dose Escalation Phase: Number of Participants with Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment [1]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of Phase 1. Phase 2 was never initiated. This decision was not based on safety concerns, but rather on the overall company strategy in adult acute myeloid leukemia (AML)
    End point type
    Primary
    End point timeframe
    Cycle 1 of induction treatment (1 cycle is 28 days)
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Participants
    2
    4
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants with at Least One Adverse Event

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    End point title
    		 Number of Participants with at Least One Adverse Event [2]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML.
    End point type
    Primary
    End point timeframe
    From Baseline until 28 days after the final dose of study drug (up to 2 years)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    4
    9
    6
    4
    No statistical analyses for this end point

    Primary: Number of Participants with Grade ≥3 Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

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    End point title
    		 Number of Participants with Grade ≥3 Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) [3]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML.
    End point type
    Primary
    End point timeframe
    From Baseline until 28 days after the final dose of study drug (up to 2 years)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Participants
    4
    9
    5
    4
    No statistical analyses for this end point

    Primary: Number of Participants Reporting Presence or Absence of Nausea Over Time, as Assessed Through Use of the National Cancer Institute (NCI) Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)

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    End point title
    		 Number of Participants Reporting Presence or Absence of Nausea Over Time, as Assessed Through Use of the National Cancer Institute (NCI) Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) [4]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE [5]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    4
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE [6]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [6] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Degree of Interference with Daily Function Caused by Nausea, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Degree of Interference with Daily Function Caused by Nausea, as Assessed Through Use of the NCI PRO-CTCAE [7]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE [8]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [8] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE [9]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE [10]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [10] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE [11]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [11] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Reported Degree of Interference with Daily Function Caused by Vomiting, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Reported Degree of Interference with Daily Function Caused by Vomiting, as Assessed Through Use of the NCI PRO-CTCAE [12]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [12] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE [13]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [13] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time

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    End point title
    		 Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time [14]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
    Notes
    [14] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE [15]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [15] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE [16]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [16] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline in Reported Degree of Interference with Daily Function Caused by Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline in Reported Degree of Interference with Daily Function Caused by Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE [17]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [17] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Change from Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE

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    End point title
    		 Change from Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE [18]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    Notes
    [18] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Participants with a Complete Remission (CR) at the End of Induction Treatment, Among Those Treated at the Recommended Phase 2 Dose

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    End point title
    		 Percentage of Participants with a Complete Remission (CR) at the End of Induction Treatment, Among Those Treated at the Recommended Phase 2 Dose [19]
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Partial data were available based on the evaluable data from the limited participants.
    End point type
    Primary
    End point timeframe
    At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
    Notes
    [19] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4 [20]
    9 [21]
    6 [22]
    4 [23]
    Units: Percentage of Participants
    number (not applicable)
        ELN Classification: Adverse
    0
    25.0
    100
    0
        ELN Classification: Favorable
    0
    100
    66.7
    0
        ELN Classification: Intermediate
    75.0
    75.0
    100
    0
    Notes
    [20] - ELN Adverse:0 ELN Favorable:0 ELN Intermediate:4
    [21] - ELN Adverse:2 ELN Favorable:1 ELN Intermediate:4
    [22] - ELN Adverse:1 ELN Favorable:3 ELN Intermediate:2
    [23] - ELN Adverse:0 ELN Favorable:0 ELN Intermediate:0
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Phases: Percentage of Participants with a CR, Complete Remission with Incomplete Blood Count Recovery (CRi), or Complete Remission with Incomplete Platelet Count Recovery (CRp) at the End of Induction Treatment

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    End point title
    		 Dose Escalation and Expansion Phases: Percentage of Participants with a CR, Complete Remission with Incomplete Blood Count Recovery (CRi), or Complete Remission with Incomplete Platelet Count Recovery (CRp) at the End of Induction Treatment
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Phases: Percentage of Participants with a CR or Complete Remission with Partial Hematologic Recovery (CRh) at the End of Induction Treatment

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    End point title
    		 Dose Escalation and Expansion Phases: Percentage of Participants with a CR or Complete Remission with Partial Hematologic Recovery (CRh) at the End of Induction Treatment
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Dose-Escalation and Expansion Phases: Percentage of Participants with a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment

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    End point title
    		 Dose-Escalation and Expansion Phases: Percentage of Participants with a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Post-Consolidation Phase: Percentage of Participants Converting from MRD-Positive to MRD-Negative Status at Any Time During Treatment

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    End point title
    		 Post-Consolidation Phase: Percentage of Participants Converting from MRD-Positive to MRD-Negative Status at Any Time During Treatment
    End point description
    Sponsor decided to not open the phase 2 portion of the study at the end of phase 1 where a RP2D was identified. This decision was not based on safety concerns, but rather on the overall company strategy in AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    At the end of maintenance treatment (12 cycles, 1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival

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    End point title
    		 Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival

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    End point title
    		 Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Percentage of Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those who Achieve Remission (CR, CRi, CRp, or CRh)

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    End point title
    		 Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those who Achieve Remission (CR, CRi, CRp, or CRh)
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    Units: Percentage of Participants
    Notes
    [24] - The study was prematurely terminated, therefore no data available
    [25] - The study was prematurely terminated, therefore no data available
    [26] - The study was prematurely terminated, therefore no data available
    [27] - The study was prematurely terminated, therefore no data available
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score

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    End point title
    		 Change from Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    0 [28]
    0 [29]
    0 [30]
    0 [31]
    Units: Score
    Notes
    [28] - The study was prematurely terminated, therefore no data available
    [29] - The study was prematurely terminated, therefore no data available
    [30] - The study was prematurely terminated, therefore no data available
    [31] - The study was prematurely terminated, therefore no data available
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Physical Function Scale Score of the Participant-Reported European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)

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    End point title
    		 Change from Baseline Over Time in Physical Function Scale Score of the Participant-Reported European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    0 [32]
    0 [33]
    0 [34]
    0 [35]
    Units: Score
    Notes
    [32] - The study was prematurely terminated, therefore no data available
    [33] - The study was prematurely terminated, therefore no data available
    [34] - The study was prematurely terminated, therefore no data available
    [35] - The study was prematurely terminated, therefore no data available
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30

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    End point title
    		 Change from Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    Units: Score
    Notes
    [36] - The study was prematurely terminated, therefore no data available
    [37] - The study was prematurely terminated, therefore no data available
    [38] - The study was prematurely terminated, therefore no data available
    [39] - The study was prematurely terminated, therefore no data available
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30

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    End point title
    		 Change from Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Headache Symptom Score of the Participant-Reported European Organisation for Research and Treatment of Cancer (EORTC) Item Library Questionnaire

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    End point title
    		 Change from Baseline Over Time in Headache Symptom Score of the Participant-Reported European Organisation for Research and Treatment of Cancer (EORTC) Item Library Questionnaire
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire

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    End point title
    		 Change from Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire

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    End point title
    		 Change from Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score

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    End point title
    		 Change from Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score

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    End point title
    		 Change from Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Score
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin

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    End point title
    		 Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: mmol/L
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: AUC of Cytarabine

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    End point title
    		 AUC of Cytarabine
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: mmol/L
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: AUC of Daunorubicin

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    End point title
    		 AUC of Daunorubicin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: mmol/L
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Idasanutlin

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Idasanutlin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: ng x hr/mL
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cmax of Cytarabine

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    End point title
    		 Cmax of Cytarabine
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: ng x hr/mL
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cmax of Daunorubicin

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    End point title
    		 Cmax of Daunorubicin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: ng x hr/mL
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Total Clearance (CL) of Idasanutlin

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    End point title
    		 Total Clearance (CL) of Idasanutlin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Hour
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: CL of Cytarabine

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    End point title
    		 CL of Cytarabine
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Hours
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: CL of Daunorubicin

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    End point title
    		 CL of Daunorubicin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Hour
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Volume of Distribution at Steady State (Vss) of Idasanutlin

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    End point title
    		 Volume of Distribution at Steady State (Vss) of Idasanutlin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    0 [40]
    0 [41]
    0 [42]
    0 [43]
    Units: Liter per Killigram
    Notes
    [40] - The study was prematurely terminated, therefore no data available
    [41] - The study was prematurely terminated, therefore no data available
    [42] - The study was prematurely terminated, therefore no data available
    [43] - The study was prematurely terminated, therefore no data available
    No statistical analyses for this end point

    Secondary: Vss of Cytarabine

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    End point title
    		 Vss of Cytarabine
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Liter per Killogram
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Vss of Daunorubicin

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    End point title
    		 Vss of Daunorubicin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Liters per Kg
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Terminal Half-Life (t1/2) of Idasanutlin

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    End point title
    		 Terminal Half-Life (t1/2) of Idasanutlin
    End point description
    Sponsor decided to not open the phase 2 portion of the study at the end of phase 1 where a RP2D was identified. This decision was not based on safety concerns, but rather on the overall company strategy in AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Minute
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: t1/2 of Cytarabine

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    End point title
    		 t1/2 of Cytarabine
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Minute
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: t1/2 of Daunorubicin

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    End point title
    		 t1/2 of Daunorubicin
    End point description
    Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
    End point type
    Secondary
    End point timeframe
    Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
    End point values
    		 Dose-Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3 Post Consolidation Cohort
    Number of subjects analysed
    4
    9
    6
    4
    Units: Minute
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 28 days
    Adverse event reporting additional description
    All AEs covered the periods of Treatment and Safety Follow-up.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    DOSE ESCALATION COHORT 1
    Reporting group description
    		 For induction, participants will be treated with idasanutlin plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin of 200 mg

    Reporting group title
    POST CONSOLIDATION PHASE COHORT
    Reporting group description
    		 Participants who are idasanutlin treatment-naive, had received induction and chemotherapy consolidation for AML outside of the study, and were in minimal residual disease (MRD)-positive remission after induction will be enrolled in this cohort to receive maintenance treatment with single-agent idasanutlin of 150 mg

    Reporting group title
    DOSE ESCALATION COHORT 3
    Reporting group description
    		 For induction, participants will be treated with idasanutlin plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin of 250 mg

    Reporting group title
    DOSE ESCALATION COHORT 2
    Reporting group description
    		 For induction, participants will be treated with idasanutlin plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin of 350 mg

    Serious adverse events
    		 DOSE ESCALATION COHORT 1 POST CONSOLIDATION PHASE COHORT DOSE ESCALATION COHORT 3 DOSE ESCALATION COHORT 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    4 / 9 (44.44%)
         number of deaths (all causes)
    2
    1
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Metapneumovirus infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DOSE ESCALATION COHORT 1 POST CONSOLIDATION PHASE COHORT DOSE ESCALATION COHORT 3 DOSE ESCALATION COHORT 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    6 / 6 (100.00%)
    9 / 9 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    0
    1
    Embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Flushing
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypertension
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hypotension
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    2 / 9 (22.22%)
         occurrences all number
    1
    0
    5
    2
    Orthostatic hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    5
    1
    0
    Catheter site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Catheter site erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Catheter site rash
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    1
    0
    2
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Face oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Fatigue
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    3 / 6 (50.00%)
    3 / 9 (33.33%)
         occurrences all number
    2
    1
    4
    3
    Generalised oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    2
    2
    Mucosal inflammation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    6 / 9 (66.67%)
         occurrences all number
    1
    0
    1
    6
    Malaise
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    5 / 6 (83.33%)
    3 / 9 (33.33%)
         occurrences all number
    2
    0
    7
    3
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    3
    2
    Peripheral swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Xerosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Physical deconditioning
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    2
    2
    Dysphonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    2
    0
    4
    2
    Haemoptysis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    2
    1
    Hiccups
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Pleuritic pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Sinus congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Anxiety
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    0
    0
    1
    Depressed mood
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    0
    3
    1
    Suicidal ideation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 6 (66.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    9
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 6 (66.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    5
    0
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    4
    1
    Blood count abnormal
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood lactic acid increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Blood uric acid decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    5
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    8
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    3
    4
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    4
    1
    Weight decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    5
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    5
    0
    Scrotal injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    1
    0
    2
    Transfusion reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    0
    2
    Vascular access complication
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pericarditis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    4
    1
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    0
    1
    Dizziness postural
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    4 / 9 (44.44%)
         occurrences all number
    1
    0
    1
    4
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    3
    1
    Hypersomnia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Restless legs syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    1
    3
    Tremor
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    4 / 9 (44.44%)
         occurrences all number
    5
    10
    4
    5
    Coagulopathy
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Febrile neutropenia
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 4 (0.00%)
    4 / 6 (66.67%)
    8 / 9 (88.89%)
         occurrences all number
    4
    0
    4
    11
    Leukopenia
         subjects affected / exposed
    2 / 4 (50.00%)
    3 / 4 (75.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    7
    14
    0
    0
    Neutropenia
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    1
    17
    1
    1
    Pancytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 4 (50.00%)
    4 / 4 (100.00%)
    3 / 6 (50.00%)
    4 / 9 (44.44%)
         occurrences all number
    8
    9
    3
    5
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Ear swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    1
    0
    0
    3
    Eye swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Papilloedema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Retinal haemorrhage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Abdominal pain
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    4 / 9 (44.44%)
         occurrences all number
    2
    0
    2
    4
    Abdominal pain lower
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Change of bowel habit
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Colitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    0
    0
    0
    3
    Constipation
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    2 / 6 (33.33%)
    3 / 9 (33.33%)
         occurrences all number
    1
    2
    2
    3
    Diarrhoea
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 4 (75.00%)
    5 / 6 (83.33%)
    9 / 9 (100.00%)
         occurrences all number
    6
    5
    9
    14
    Dry mouth
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    3
    0
    1
    2
    Dysphagia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    2
    1
    Gingival swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematemesis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematochezia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Hyperchlorhydria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Ileus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Large intestinal obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Melaena
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    3 / 4 (75.00%)
    4 / 4 (100.00%)
    4 / 6 (66.67%)
    8 / 9 (88.89%)
         occurrences all number
    3
    6
    5
    11
    Odynophagia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Oesophageal pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oesophagitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Oesophagitis haemorrhagic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Oral disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oral pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    1
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Proctalgia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Salivary hypersecretion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Stomatitis
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    2 / 9 (22.22%)
         occurrences all number
    5
    0
    3
    3
    Tongue discolouration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tongue ulceration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    3 / 6 (50.00%)
    4 / 9 (44.44%)
         occurrences all number
    4
    3
    4
    5
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cholelithiasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Hepatocellular injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Angioedema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blister
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood blister
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    1
    1
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    4
    3
    Exfoliative rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Leukoplakia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Night sweats
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Onychalgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Pain of skin
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    2
    1
    Palmar erythema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    2
    0
    0
    5
    Papule
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 6 (66.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    5
    2
    Purpura
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    4 / 6 (66.67%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    4
    3
    Rash erythematous
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Rash macular
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    2
    2
    Rash morbilliform
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash pruritic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Toxic erythema of chemotherapy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Transient acantholytic dermatosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Glycosuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    2
    1
    Proteinuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    1
    0
    0
    2
    Back pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gouty arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Muscle fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Muscular weakness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    3
    0
    0
    1
    Neck pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    1
    Infections and infestations
    Bacillus bacteraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Bacteraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    0
    0
    0
    3
    COVID-19
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bacteroides bacteraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    3
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    0
    1
    Cystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Endophthalmitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Enterocolitis bacterial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    2
    Influenza
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    3 / 9 (33.33%)
         occurrences all number
    0
    0
    1
    3
    Paronychia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    2
    4
    1
    2
    Fluid overload
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    2
    0
    1
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    15
    0
    Gout
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperphosphataemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    1
    1
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    7
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    4 / 6 (66.67%)
    3 / 9 (33.33%)
         occurrences all number
    1
    1
    11
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    8
    1
    Hypomagnesaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 6 (66.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    6
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    3 / 9 (33.33%)
         occurrences all number
    1
    0
    5
    3
    Metabolic acidosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    1

    More information

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

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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.

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