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    Clinical Trial Results:
    A Randomized (1:1), Double-blind, Multi-center, Placebo Controlled Study Evaluating Intensive Chemotherapy With or Without Glasdegib (Pf-04449913) or Azacitidine (AZA) With or Without Glasdegib in Patients With Previously Untreated Acute Myeloid Leukemia

    Summary
    EudraCT number
    		 2017-002822-19
    Trial protocol
    		 FR   GB   CZ   SE   BE   PL   ES   DE   IT   RO  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    04 Aug 2021
    First version publication date
    04 Aug 2021
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    B1371019
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    Interim
    Date of interim/final analysis
    05 Jun 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jun 2020
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that glasdegib is superior to placebo in combination with azacitidine (non-intensive study) or cytarabine and daunorubicin (intensive study) in prolonging OS in subjects with untreated acute myeloid leukemia (AML).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Apr 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    China: 72
    Country: Number of subjects enrolled
    Czechia: 60
    Country: Number of subjects enrolled
    France: 29
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Hungary: 36
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Japan: 85
    Country: Number of subjects enrolled
    Korea, Republic of: 29
    Country: Number of subjects enrolled
    Poland: 24
    Country: Number of subjects enrolled
    Romania: 8
    Country: Number of subjects enrolled
    Russian Federation: 33
    Country: Number of subjects enrolled
    Spain: 72
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    Taiwan: 19
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    United States: 143
    Country: Number of subjects enrolled
    Austria: 15
    Country: Number of subjects enrolled
    Mexico: 3
    Worldwide total number of subjects
    729
    EEA total number of subjects
    287
    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)
    318
    From 65 to 84 years
    396
    85 years and over
    15

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study evaluated glasdegib in intensive and non-intensive (NI) chemotherapy populations. Intensive study: Glasdegib was studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (AML).

    Pre-assignment
    Screening details
    		 NI study: Glasdegib was studied in combination with azacitidine for treatment of adults with previously untreated AML who were not candidates for intensive induction chemotherapy. Results are reported at primary completion date and data is reported only for primary endpoint. Data for secondary endpoint will be posted at secondary completion date.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Intensive Study: Glasdegib + Cytarabine + Daunorubicin
    Arm description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib 100 mg tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. Follow up (FU) was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Glasdegib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Glasdegib 100 mg tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive (complete remission) CR MRD-negative central laboratory results, whichever came first.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Cytarabine 100 mg/m^2 daily by IV infusion for 7 days. If greater than or equals to (>=) 5 percent (%) bone marrow blast or investigator judgement for less than (<) 5% bone marrow blasts then subjects received either option 1: cytarabine 100 mg/m^2 IV daily for 5 days or option 2: cytarabine 100 mg/m^2 IV daily for 7 days.

    Investigational medicinal product name
    Daunorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daunorubicin 60 mg/m^2 daily IV for 3 days. If >=5% bone marrow blast or investigator judgement for < 5% bone marrow blasts then received daunorubicin 60 mg/m^2 IV daily for 2 days or daunorubicin 60 mg/m^2 IV daily for 3 days.

    Arm title
    		 Intensive Study: Placebo + Cytarabine + Daunorubicin
    Arm description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib matched placebo tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. FU was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Glasdegib matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative central laboratory results, whichever came first.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Cytarabine 100 mg/m^2 daily by IV infusion for 7 days. If >=5% bone marrow blast or investigator judgement for <5% bone marrow blasts then subjects received either option 1: cytarabine 100 mg/m^2 IV daily for 5 days or option 2: cytarabine 100 mg/m^2 IV daily for 7 days.

    Investigational medicinal product name
    Daunorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daunorubicin 60 mg/m^2 daily IV for 3 days. If >=5% bone marrow blast or investigator judgement for < 5% bone marrow blasts then received daunorubicin 60 mg/m^2 IV daily for 2 days or daunorubicin 60 mg/m^2 IV daily for 3 days.

    Arm title
    		 Non-intensive Study: Glasdegib + Azacitidine
    Arm description
    		 Subjects received chemotherapy with azacitidine 75 milligram per square meter (mg/m^2) subcutaneous (SC) injection or intravenous (IV) infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subject refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent hematopoietic stem cell transplantation (HSCT) per local standard of care and received glasdegib up to 2 years following randomization unless 2 consecutive negative minimal residual disease (MRD) assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Glasdegib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received glasdegib 100 mg PO QD from Day 1 of chemotherapy and continued if subject’s demonstrated reasonable evidence of clinical benefit or until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first.

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, patient refusal or death, whichever occurred first.

    Arm title
    		 Non-intensive Study: Placebo + Azacitidine
    Arm description
    		 Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subjects refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent HSCT per local standard of care and glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Glasdegib matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received glasdegib 100 mg matching placebo PO QD from Day 1 of chemotherapy and continued if subject’s demonstrated reasonable evidence of clinical benefit or until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first.

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, patient refusal or death, whichever occurred first.

    Number of subjects in period 1
    		Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
    Started
    201
    203
    163
    162
    Completed
    0
    0
    0
    0
    Not completed
    201
    203
    163
    162
         Adverse event, serious fatal
    67
    60
    96
    88
         Consent withdrawn by subject
    13
    19
    5
    6
         Ongoing
    121
    123
    62
    66
         Unspecified
    -
    1
    -
    -
         Lost to follow-up
    -
    -
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Intensive Study: Glasdegib + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib 100 mg tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. Follow up (FU) was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Intensive Study: Placebo + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib matched placebo tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. FU was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Non-intensive Study: Glasdegib + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 milligram per square meter (mg/m^2) subcutaneous (SC) injection or intravenous (IV) infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subject refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent hematopoietic stem cell transplantation (HSCT) per local standard of care and received glasdegib up to 2 years following randomization unless 2 consecutive negative minimal residual disease (MRD) assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Reporting group title
    Non-intensive Study: Placebo + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subjects refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent HSCT per local standard of care and glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Reporting group values
    		 Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine Total
    Number of subjects
    		 201 203 163 162 729
    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)
    		 144 141 16 17 318
        From 65-84 years
    		 57 61 142 136 396
        85 years and over
    		 0 1 5 9 15
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.55 ± 12.60 55.38 ± 13.61 73.19 ± 7.17 73.14 ± 6.82 -
    Sex: Female, Male
    Units: subjects
        Female
    		 71 97 97 89 354
        Male
    		 130 106 66 73 375
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 0 0 1
        Asian
    		 66 57 51 44 218
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 3 3 1 7 14
        White
    		 110 123 97 99 429
        More than one race
    		 1 0 0 0 1
        Unknown or Not Reported
    		 20 20 14 12 66
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 19 12 12 16 59
        Not Hispanic or Latino
    		 166 171 140 139 616
        Unknown or Not Reported
    		 16 20 11 7 54

    End points

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    End points reporting groups
    Reporting group title
    Intensive Study: Glasdegib + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib 100 mg tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. Follow up (FU) was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Intensive Study: Placebo + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib matched placebo tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. FU was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Non-intensive Study: Glasdegib + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 milligram per square meter (mg/m^2) subcutaneous (SC) injection or intravenous (IV) infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subject refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent hematopoietic stem cell transplantation (HSCT) per local standard of care and received glasdegib up to 2 years following randomization unless 2 consecutive negative minimal residual disease (MRD) assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Reporting group title
    Non-intensive Study: Placebo + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subjects refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent HSCT per local standard of care and glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Primary: Intensive Study: Overall Survival (OS)

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    End point title
    		 Intensive Study: Overall Survival (OS) [1]
    End point description
    OS is defined as the time from the date of randomization to the date of death due to any cause. Subjects last known to be alive were to be censored at the date of last contact. FA set included all randomised subjects. Here, '99999 =Upper limit of 95 % CI was not estimable due to low number of subjects with events.'
    End point type
    Primary
    End point timeframe
    Baseline up to 25 months
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistics were only planned for the arms specified
    End point values
    		 Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
    Number of subjects analysed
    201
    203
    Units: months
        median (confidence interval 95%)
    17.3 (15.2 to 18.5)
    20.4 (17.6 to 99999)
    Statistical analysis title
    		 Glasdegib Vs Placebo
    Statistical analysis description
    Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio less than (<) 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2 compared to Placebo + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2.
    Comparison groups
    Intensive Study: Glasdegib + Cytarabine + Daunorubicin v Intensive Study: Placebo + Cytarabine + Daunorubicin
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6579
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.755
         upper limit
    		 1.532

    Primary: Non-intensive Study: Overall Survival (OS)

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    End point title
    		 Non-intensive Study: Overall Survival (OS) [2]
    End point description
    Overall survival (OS) was defined as the time from date of first study treatment to date of death from any cause. Subject's last known to be alive were to be censored at the date of last contact. FA set included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Baseline up to 25 months
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistics were only planned for the arms specified
    End point values
    		 Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
    Number of subjects analysed
    163
    162
    Units: months
        median (confidence interval 95%)
    10.3 (7.7 to 12.4)
    10.6 (8.4 to 13.3)
    Statistical analysis title
    		 Glasdegib Vs Placebo
    Statistical analysis description
    Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio < 1 indicates a reduction in hazard rate in favor of Glasdegib 100 mg PO QD + Azacitidine compared to Placebo + Azacitidine
    Comparison groups
    Non-intensive Study: Glasdegib + Azacitidine v Non-intensive Study: Placebo + Azacitidine
    Number of subjects included in analysis
    325
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5955
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.775
         upper limit
    		 1.388

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 28 days from last dose of study drug (up to 25 months)
    Adverse event reporting additional description
    Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Safety analysis (SA) set included all subjects who received at least one dose of study drug.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Intensive Study: Glasdegib + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib 100 mg tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. FU was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Intensive Study: Placebo + Cytarabine + Daunorubicin
    Reporting group description
    		 Subjects received 28 days induction therapy: Cytarabine 100 mg/m^2 IV daily for 7 days + daunorubicin 60 mg/m^2 daily IV for 3 days. Depending on bone marrow blast or investigator judgement subjects had second induction to receive either same therapy or cytarabine 100 mg/m^2 IV daily for 5 days + daunorubicin 60 mg/m^2 IV daily for 2 days. Subjects with <5% bone marrow blasts entered consolation phase: treated with either or both of: 1) Cytarabine 1 to 3 gm/m^2 IV for adults >= 60 to <60 years twice daily on Days 1, 3, 5 for 4 cycle (1 cycle=28 days) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Subjects received Glasdegib matched placebo tablet PO QD from Day 1 up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative, whichever came first. FU was up to 2 years from last dose and long term survival FU from last subject randomized up to 5 years or until death or consent withdrawal.

    Reporting group title
    Non-intensive Study: Glasdegib + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subject refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg orally PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent HSCT per local standard of care and received glasdegib up to 2 years following randomization unless 2 consecutive negative MRD assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Reporting group title
    Non-intensive Study: Placebo + Azacitidine
    Reporting group description
    		 Subjects received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, subjects refusal or death, whichever occurred first. Subjects also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible subjects underwent HSCT per local standard of care and glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Subjects were followed up for first 2 years from last dose of drug and had long term follow-up for survival for up to 5 years from randomization of last subject in study, or until death, or consent withdrawal.

    Serious adverse events
    		 Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    85 / 198 (42.93%)
    91 / 201 (45.27%)
    110 / 162 (67.90%)
    118 / 160 (73.75%)
         number of deaths (all causes)
    67
    60
    96
    88
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Differentiation syndrome
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal neoplasm
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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 / 1
    Neoplasm progression
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Neoplasm prostate
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Embolism
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Orthostatic hypotension
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Aneurysm ruptured
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Circulatory collapse
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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 / 1
    Peripheral ischaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Thrombosis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Venous thrombosis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    2 / 198 (1.01%)
    4 / 201 (1.99%)
    14 / 162 (8.64%)
    22 / 160 (13.75%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 15
    0 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 198 (2.02%)
    6 / 201 (2.99%)
    9 / 162 (5.56%)
    11 / 160 (6.88%)
         occurrences causally related to treatment / all
    1 / 4
    3 / 6
    3 / 10
    3 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Chills
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Malaise
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Mucosal inflammation
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Asthenia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    4 / 162 (2.47%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
    Sudden death
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Fatigue
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    3 / 160 (1.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue inflammation
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Immune system disorders
    Graft versus host disease
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Graft versus host disease in skin
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Cytokine release syndrome
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    3 / 162 (1.85%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 198 (1.01%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 198 (0.51%)
    4 / 201 (1.99%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 198 (0.51%)
    3 / 201 (1.49%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 198 (0.51%)
    2 / 201 (1.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Pneumonia aspiration
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    3 / 160 (1.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Pulmonary oedema
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adjustment disorder with depressed mood
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Hallucination
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    13 / 198 (6.57%)
    8 / 201 (3.98%)
    5 / 162 (3.09%)
    3 / 160 (1.88%)
         occurrences causally related to treatment / all
    9 / 15
    8 / 10
    3 / 5
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 198 (0.51%)
    2 / 201 (1.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 198 (0.51%)
    2 / 201 (1.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 198 (1.01%)
    3 / 201 (1.49%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Creatinine renal clearance decreased
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electroencephalogram abnormal
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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 / 1
    Weight decreased
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Splenic rupture
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Femoral neck fracture
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Post procedural complication
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Subdural haematoma
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Subdural haemorrhage
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Tooth fracture
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Transfusion reaction
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    3 / 198 (1.52%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Cardiomyopathy
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracardiac mass
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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 / 1
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Bradycardia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Ventricular fibrillation
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 198 (1.01%)
    2 / 201 (1.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Central nervous system lesion
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Cerebral infarction
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Intracranial aneurysm
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 198 (1.01%)
    1 / 201 (0.50%)
    5 / 162 (3.09%)
    5 / 160 (3.13%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    1 / 6
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    18 / 198 (9.09%)
    17 / 201 (8.46%)
    24 / 162 (14.81%)
    18 / 160 (11.25%)
         occurrences causally related to treatment / all
    20 / 26
    22 / 23
    14 / 33
    6 / 27
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Neutropenia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 198 (0.51%)
    3 / 201 (1.49%)
    2 / 162 (1.23%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    1 / 1
    28 / 28
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Splenic necrosis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    4 / 162 (2.47%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 5
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    3 / 162 (1.85%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 198 (1.52%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 198 (1.01%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Intussusception
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Proctalgia
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Abdominal pain
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Mechanical ileus
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Pancreatitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Gastrointestinal perforation
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glossitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids thrombosed
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Ileus
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 198 (1.01%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Cholangitis acute
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Rash maculo-papular
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Dermatitis exfoliative generalised
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 198 (1.01%)
    3 / 201 (1.49%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Haematuria
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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 / 1
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Osteoarthritis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Soft tissue necrosis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Arthritis infective
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    4 / 198 (2.02%)
    2 / 201 (1.00%)
    3 / 162 (1.85%)
    4 / 160 (2.50%)
         occurrences causally related to treatment / all
    5 / 6
    0 / 2
    1 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    7 / 160 (4.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    3 / 198 (1.52%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    5 / 160 (3.13%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    1 / 1
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 198 (0.51%)
    2 / 201 (1.00%)
    3 / 162 (1.85%)
    5 / 160 (3.13%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Perirectal abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    15 / 198 (7.58%)
    11 / 201 (5.47%)
    26 / 162 (16.05%)
    35 / 160 (21.88%)
         occurrences causally related to treatment / all
    9 / 22
    3 / 13
    9 / 38
    9 / 49
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    0 / 9
    1 / 9
    Pneumonia fungal
         subjects affected / exposed
    2 / 198 (1.01%)
    2 / 201 (1.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 3
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    15 / 198 (7.58%)
    13 / 201 (6.47%)
    13 / 162 (8.02%)
    9 / 160 (5.63%)
         occurrences causally related to treatment / all
    12 / 26
    10 / 14
    5 / 18
    3 / 13
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    1 / 6
    1 / 4
    Septic shock
         subjects affected / exposed
    2 / 198 (1.01%)
    4 / 201 (1.99%)
    4 / 162 (2.47%)
    5 / 160 (3.13%)
         occurrences causally related to treatment / all
    1 / 2
    4 / 4
    3 / 7
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    1 / 3
    Soft tissue infection
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    3 / 160 (1.88%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    9 / 162 (5.56%)
    4 / 160 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    3 / 13
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anorectal infection
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Atypical pneumonia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Brain abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Candida pneumonia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium bacteraemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related bacteraemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Disseminated varicella zoster virus infection
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    2 / 198 (1.01%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 198 (0.51%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fungal sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Herpes ophthalmic
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Herpes zoster
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal bacteraemia
         subjects affected / exposed
    3 / 198 (1.52%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Streptococcal sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    1 / 198 (0.51%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (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
    Abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Anal abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Bronchitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Candida sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Device related infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Herpes dermatitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Infected skin ulcer
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Periodontitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Post procedural infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    2 / 160 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Skin infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Subdiaphragmatic abscess
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Suspected COVID-19
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Systemic infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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
    Systemic mycosis
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral infection
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    0 / 160 (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
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    3 / 162 (1.85%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    1 / 201 (0.50%)
    0 / 162 (0.00%)
    0 / 160 (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
    Failure to thrive
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    1 / 160 (0.63%)
         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 / 1
    Hyperkalaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    3 / 160 (1.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    2 / 162 (1.23%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    1 / 162 (0.62%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    		 Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    194 / 198 (97.98%)
    195 / 201 (97.01%)
    153 / 162 (94.44%)
    149 / 160 (93.13%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    10 / 198 (5.05%)
    25 / 201 (12.44%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    15
    39
    0
    0
    Hypotension
         subjects affected / exposed
    18 / 198 (9.09%)
    17 / 201 (8.46%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    19
    23
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    15 / 198 (7.58%)
    11 / 201 (5.47%)
    15 / 162 (9.26%)
    18 / 160 (11.25%)
         occurrences all number
    21
    14
    24
    40
    Fatigue
         subjects affected / exposed
    31 / 198 (15.66%)
    32 / 201 (15.92%)
    13 / 162 (8.02%)
    23 / 160 (14.38%)
         occurrences all number
    53
    47
    17
    32
    Oedema peripheral
         subjects affected / exposed
    25 / 198 (12.63%)
    32 / 201 (15.92%)
    11 / 162 (6.79%)
    18 / 160 (11.25%)
         occurrences all number
    36
    43
    13
    25
    Pyrexia
         subjects affected / exposed
    84 / 198 (42.42%)
    84 / 201 (41.79%)
    41 / 162 (25.31%)
    39 / 160 (24.38%)
         occurrences all number
    194
    169
    68
    65
    Chills
         subjects affected / exposed
    20 / 198 (10.10%)
    11 / 201 (5.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    25
    17
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    12 / 198 (6.06%)
    7 / 201 (3.48%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    16
    9
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    13 / 198 (6.57%)
    8 / 201 (3.98%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    16
    10
    0
    0
    Oedema
         subjects affected / exposed
    9 / 198 (4.55%)
    19 / 201 (9.45%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    17
    22
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    11 / 162 (6.79%)
    7 / 160 (4.38%)
         occurrences all number
    0
    0
    42
    19
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    23 / 198 (11.62%)
    23 / 201 (11.44%)
    10 / 162 (6.17%)
    20 / 160 (12.50%)
         occurrences all number
    28
    25
    10
    26
    Dyspnoea
         subjects affected / exposed
    15 / 198 (7.58%)
    23 / 201 (11.44%)
    11 / 162 (6.79%)
    18 / 160 (11.25%)
         occurrences all number
    18
    25
    11
    25
    Epistaxis
         subjects affected / exposed
    19 / 198 (9.60%)
    20 / 201 (9.95%)
    8 / 162 (4.94%)
    10 / 160 (6.25%)
         occurrences all number
    21
    25
    16
    14
    Oropharyngeal pain
         subjects affected / exposed
    19 / 198 (9.60%)
    19 / 201 (9.45%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    23
    21
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    27 / 198 (13.64%)
    30 / 201 (14.93%)
    12 / 162 (7.41%)
    8 / 160 (5.00%)
         occurrences all number
    29
    37
    15
    13
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    39 / 198 (19.70%)
    53 / 201 (26.37%)
    13 / 162 (8.02%)
    11 / 160 (6.88%)
         occurrences all number
    104
    138
    27
    20
    Aspartate aminotransferase increased
         subjects affected / exposed
    30 / 198 (15.15%)
    41 / 201 (20.40%)
    10 / 162 (6.17%)
    9 / 160 (5.63%)
         occurrences all number
    51
    83
    17
    20
    Blood creatinine increased
         subjects affected / exposed
    18 / 198 (9.09%)
    13 / 201 (6.47%)
    20 / 162 (12.35%)
    13 / 160 (8.13%)
         occurrences all number
    24
    20
    34
    15
    Electrocardiogram QT prolonged
         subjects affected / exposed
    21 / 198 (10.61%)
    20 / 201 (9.95%)
    20 / 162 (12.35%)
    19 / 160 (11.88%)
         occurrences all number
    30
    35
    28
    33
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    12 / 198 (6.06%)
    22 / 201 (10.95%)
    10 / 162 (6.17%)
    8 / 160 (5.00%)
         occurrences all number
    36
    75
    19
    13
    Neutrophil count decreased
         subjects affected / exposed
    56 / 198 (28.28%)
    49 / 201 (24.38%)
    22 / 162 (13.58%)
    22 / 160 (13.75%)
         occurrences all number
    308
    317
    129
    153
    Platelet count decreased
         subjects affected / exposed
    77 / 198 (38.89%)
    73 / 201 (36.32%)
    30 / 162 (18.52%)
    26 / 160 (16.25%)
         occurrences all number
    627
    504
    155
    162
    Weight decreased
         subjects affected / exposed
    21 / 198 (10.61%)
    22 / 201 (10.95%)
    34 / 162 (20.99%)
    19 / 160 (11.88%)
         occurrences all number
    37
    32
    63
    36
    White blood cell count decreased
         subjects affected / exposed
    63 / 198 (31.82%)
    53 / 201 (26.37%)
    17 / 162 (10.49%)
    18 / 160 (11.25%)
         occurrences all number
    454
    495
    114
    143
    Blood alkaline phosphatase increased
         subjects affected / exposed
    14 / 198 (7.07%)
    13 / 201 (6.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    26
    21
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    25 / 198 (12.63%)
    13 / 201 (6.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    62
    34
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    19 / 198 (9.60%)
    21 / 201 (10.45%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    133
    111
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    7 / 162 (4.32%)
    9 / 160 (5.63%)
         occurrences all number
    0
    0
    13
    20
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    10 / 162 (6.17%)
    10 / 160 (6.25%)
         occurrences all number
    0
    0
    19
    11
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    11 / 198 (5.56%)
    7 / 201 (3.48%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    13
    7
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    23 / 198 (11.62%)
    18 / 201 (8.96%)
    9 / 162 (5.56%)
    14 / 160 (8.75%)
         occurrences all number
    32
    26
    9
    24
    Dysgeusia
         subjects affected / exposed
    39 / 198 (19.70%)
    20 / 201 (9.95%)
    37 / 162 (22.84%)
    8 / 160 (5.00%)
         occurrences all number
    48
    21
    41
    8
    Headache
         subjects affected / exposed
    39 / 198 (19.70%)
    47 / 201 (23.38%)
    4 / 162 (2.47%)
    9 / 160 (5.63%)
         occurrences all number
    56
    62
    4
    20
    Paraesthesia
         subjects affected / exposed
    11 / 198 (5.56%)
    0 / 201 (0.00%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    11
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    101 / 198 (51.01%)
    97 / 201 (48.26%)
    73 / 162 (45.06%)
    70 / 160 (43.75%)
         occurrences all number
    553
    530
    217
    335
    Febrile neutropenia
         subjects affected / exposed
    97 / 198 (48.99%)
    96 / 201 (47.76%)
    22 / 162 (13.58%)
    20 / 160 (12.50%)
         occurrences all number
    134
    152
    32
    37
    Leukopenia
         subjects affected / exposed
    10 / 198 (5.05%)
    13 / 201 (6.47%)
    11 / 162 (6.79%)
    4 / 160 (2.50%)
         occurrences all number
    34
    65
    52
    10
    Neutropenia
         subjects affected / exposed
    41 / 198 (20.71%)
    43 / 201 (21.39%)
    35 / 162 (21.60%)
    30 / 160 (18.75%)
         occurrences all number
    96
    180
    130
    120
    Thrombocytopenia
         subjects affected / exposed
    52 / 198 (26.26%)
    52 / 201 (25.87%)
    37 / 162 (22.84%)
    32 / 160 (20.00%)
         occurrences all number
    271
    324
    152
    123
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    31 / 198 (15.66%)
    29 / 201 (14.43%)
    12 / 162 (7.41%)
    10 / 160 (6.25%)
         occurrences all number
    37
    38
    13
    12
    Constipation
         subjects affected / exposed
    71 / 198 (35.86%)
    61 / 201 (30.35%)
    58 / 162 (35.80%)
    50 / 160 (31.25%)
         occurrences all number
    96
    87
    90
    69
    Diarrhoea
         subjects affected / exposed
    96 / 198 (48.48%)
    88 / 201 (43.78%)
    36 / 162 (22.22%)
    31 / 160 (19.38%)
         occurrences all number
    141
    133
    49
    46
    Haemorrhoids
         subjects affected / exposed
    13 / 198 (6.57%)
    19 / 201 (9.45%)
    8 / 162 (4.94%)
    10 / 160 (6.25%)
         occurrences all number
    13
    21
    11
    10
    Nausea
         subjects affected / exposed
    110 / 198 (55.56%)
    106 / 201 (52.74%)
    55 / 162 (33.95%)
    44 / 160 (27.50%)
         occurrences all number
    169
    181
    96
    70
    Vomiting
         subjects affected / exposed
    57 / 198 (28.79%)
    40 / 201 (19.90%)
    35 / 162 (21.60%)
    32 / 160 (20.00%)
         occurrences all number
    77
    57
    47
    44
    Abdominal pain upper
         subjects affected / exposed
    12 / 198 (6.06%)
    9 / 201 (4.48%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    12
    12
    0
    0
    Dyspepsia
         subjects affected / exposed
    12 / 198 (6.06%)
    5 / 201 (2.49%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    13
    5
    0
    0
    Proctalgia
         subjects affected / exposed
    14 / 198 (7.07%)
    6 / 201 (2.99%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    15
    7
    0
    0
    Stomatitis
         subjects affected / exposed
    29 / 198 (14.65%)
    41 / 201 (20.40%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    45
    55
    0
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 198 (0.00%)
    0 / 201 (0.00%)
    11 / 162 (6.79%)
    0 / 160 (0.00%)
         occurrences all number
    0
    0
    18
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    22 / 198 (11.11%)
    26 / 201 (12.94%)
    20 / 162 (12.35%)
    3 / 160 (1.88%)
         occurrences all number
    26
    29
    22
    3
    Pruritus
         subjects affected / exposed
    12 / 198 (6.06%)
    11 / 201 (5.47%)
    8 / 162 (4.94%)
    9 / 160 (5.63%)
         occurrences all number
    12
    19
    8
    9
    Rash
         subjects affected / exposed
    46 / 198 (23.23%)
    51 / 201 (25.37%)
    10 / 162 (6.17%)
    13 / 160 (8.13%)
         occurrences all number
    70
    80
    12
    16
    Dry skin
         subjects affected / exposed
    13 / 198 (6.57%)
    10 / 201 (4.98%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    13
    12
    0
    0
    Petechiae
         subjects affected / exposed
    8 / 198 (4.04%)
    11 / 201 (5.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    10
    11
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    21 / 198 (10.61%)
    21 / 201 (10.45%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    26
    30
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    17 / 198 (8.59%)
    14 / 201 (6.97%)
    11 / 162 (6.79%)
    11 / 160 (6.88%)
         occurrences all number
    23
    16
    13
    20
    Back pain
         subjects affected / exposed
    22 / 198 (11.11%)
    17 / 201 (8.46%)
    7 / 162 (4.32%)
    12 / 160 (7.50%)
         occurrences all number
    24
    18
    8
    15
    Muscle spasms
         subjects affected / exposed
    20 / 198 (10.10%)
    3 / 201 (1.49%)
    28 / 162 (17.28%)
    4 / 160 (2.50%)
         occurrences all number
    31
    3
    44
    4
    Myalgia
         subjects affected / exposed
    15 / 198 (7.58%)
    11 / 201 (5.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    27
    12
    0
    0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    32 / 198 (16.16%)
    33 / 201 (16.42%)
    19 / 162 (11.73%)
    15 / 160 (9.38%)
         occurrences all number
    44
    53
    27
    19
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 198 (4.55%)
    11 / 201 (5.47%)
    12 / 162 (7.41%)
    11 / 160 (6.88%)
         occurrences all number
    13
    16
    14
    11
    Urinary tract infection
         subjects affected / exposed
    5 / 198 (2.53%)
    11 / 201 (5.47%)
    16 / 162 (9.88%)
    9 / 160 (5.63%)
         occurrences all number
    5
    12
    24
    11
    Bacteraemia
         subjects affected / exposed
    16 / 198 (8.08%)
    11 / 201 (5.47%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    20
    14
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    52 / 198 (26.26%)
    41 / 201 (20.40%)
    45 / 162 (27.78%)
    21 / 160 (13.13%)
         occurrences all number
    67
    68
    55
    32
    Hyperglycaemia
         subjects affected / exposed
    10 / 198 (5.05%)
    10 / 201 (4.98%)
    5 / 162 (3.09%)
    9 / 160 (5.63%)
         occurrences all number
    12
    17
    5
    19
    Hypoalbuminaemia
         subjects affected / exposed
    32 / 198 (16.16%)
    30 / 201 (14.93%)
    11 / 162 (6.79%)
    13 / 160 (8.13%)
         occurrences all number
    78
    57
    28
    28
    Hypocalcaemia
         subjects affected / exposed
    25 / 198 (12.63%)
    17 / 201 (8.46%)
    10 / 162 (6.17%)
    13 / 160 (8.13%)
         occurrences all number
    41
    37
    25
    32
    Hypokalaemia
         subjects affected / exposed
    76 / 198 (38.38%)
    83 / 201 (41.29%)
    35 / 162 (21.60%)
    22 / 160 (13.75%)
         occurrences all number
    200
    217
    65
    42
    Hypomagnesaemia
         subjects affected / exposed
    29 / 198 (14.65%)
    24 / 201 (11.94%)
    11 / 162 (6.79%)
    5 / 160 (3.13%)
         occurrences all number
    52
    49
    17
    6
    Hyponatraemia
         subjects affected / exposed
    24 / 198 (12.12%)
    15 / 201 (7.46%)
    16 / 162 (9.88%)
    9 / 160 (5.63%)
         occurrences all number
    34
    23
    21
    19
    Hypophosphataemia
         subjects affected / exposed
    42 / 198 (21.21%)
    44 / 201 (21.89%)
    10 / 162 (6.17%)
    15 / 160 (9.38%)
         occurrences all number
    88
    84
    21
    30
    Hyperuricaemia
         subjects affected / exposed
    13 / 198 (6.57%)
    9 / 201 (4.48%)
    0 / 162 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    20
    28
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Nov 2017
    In schedule of activities of Intenstive study, pregnancy testing added for Day 1 of each Consolidation Cycle with single-agent cytarabine and Day 1 of each cycle where single-agent glasdegib/placebo administered to ensure appropriate safety monitoring.

    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.
    Inadvertently 1 subject was enrolled twice into the study resulting in enrollment number as 730. However, a total of 729 subject were randomized and received treatment in the study.
    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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