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    Clinical Trial Results:
    An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime-Avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram-Negative Pathogens

    Summary
    EudraCT number
    2012-000726-21
    Trial protocol
    BE   DE   CZ   ES   GR   BG   HU   IT   GB  
    Global end of trial date
    29 Sep 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Apr 2016
    First version publication date
    27 Apr 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D4280C00006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    151 85 Södertälje, Södertälje, Sweden,
    Public contact
    Nell Moore, AstraZeneca, UK 44 788-411-5907, Nell.Moore@astrazeneca.com
    Scientific contact
    Leanne Gasink, AstraZeneca, USA 302-885-5550, Leanne.Gasink@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Mar 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Sep 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To estimate the per-patient clinical response to ceftazidime-avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy (BAT) at Test of Cure (TOC) in the treatment of selected serious infections caused by ceftazidime-resistant Gram-negative pathogens.
    Protection of trial subjects
    The study will be performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with the International Conference on Harmonisation (ICH) harmonised tripartite guideline E6(R1): Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Jan 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 91
    Country: Number of subjects enrolled
    Croatia: 12
    Country: Number of subjects enrolled
    Czech Republic: 6
    Country: Number of subjects enrolled
    Romania: 31
    Country: Number of subjects enrolled
    Russian Federation: 74
    Country: Number of subjects enrolled
    Turkey: 23
    Country: Number of subjects enrolled
    Ukraine: 31
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    United States: 9
    Country: Number of subjects enrolled
    Argentina: 9
    Country: Number of subjects enrolled
    Israel: 17
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Mexico: 7
    Country: Number of subjects enrolled
    Peru: 9
    Country: Number of subjects enrolled
    South Africa: 2
    Worldwide total number of subjects
    333
    EEA total number of subjects
    147
    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)
    159
    From 65 to 84 years
    163
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 333 patients were randomized in 53 centers in 16 countries: 306 patients had cUTI and 27 patients had cIAI. The first patient was randomized on 07 January 2013 and the last patient was randomized on 29 August 2014. One patient in the CAZ-AVI arm was randomized but did not receive study drug.

    Pre-assignment
    Screening details
    None

    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
    Investigator, Monitor, Carer, Data analyst, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    cIAI:Best Available Therapy
    Arm description
    cIAI: Best Available Therapy Determinated by Investigator
    Arm type
    Active comparator

    Investigational medicinal product name
    Investigator-determined BAT(protocol preferred BAT options: meropenem,imipenem,doripenem,tigecycline, and colistin (if colistin,metronidazole should be added)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Details for dose and frequency of administration of BAT can be found.

    Arm title
    cIAI:CAZ-AVI + metronidazole
    Arm description
    cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)
    Arm type
    Experimental

    Investigational medicinal product name
    Metronidazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Metronidazole 500 mg/100 mL solution for infusion

    Investigational medicinal product name
    CAZ-AVI (single-vial product supply)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Sterile crystalline powder, 2000 mg ceftazidime/500 mg avibactam for solution for infusion

    Arm title
    cUTI:Best Available Therapy
    Arm description
    cUTI:Best Available Therapy Determinated by Investigator
    Arm type
    Active comparator

    Investigational medicinal product name
    Investigator-determined BAT(protocol preferred BAT options: meropenem,imipenem,doripenem,tigecycline, and colistin (if colistin,metronidazole should be added)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Details for dose and frequency of administration of BAT can be found.

    Arm title
    cUTI:CAZ-AVI
    Arm description
    cUTI: CAZ-AVI
    Arm type
    Experimental

    Investigational medicinal product name
    CAZ-AVI (single-vial product supply)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Sterile crystalline powder, 2000 mg ceftazidime/500 mg avibactam for

    Number of subjects in period 1
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Started
    15
    12
    153
    153
    Completed
    13
    12
    148
    143
    Not completed
    2
    0
    5
    10
         Other Eligibility criteria
             -
             -
             -
             2
         Adverse event, serious fatal
             1
             -
             3
             3
         Consent withdrawn by subject
             1
             -
             2
             1
         Lost to follow-up
             -
             -
             -
             4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    cIAI:Best Available Therapy
    Reporting group description
    cIAI: Best Available Therapy Determinated by Investigator

    Reporting group title
    cIAI:CAZ-AVI + metronidazole
    Reporting group description
    cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)

    Reporting group title
    cUTI:Best Available Therapy
    Reporting group description
    cUTI:Best Available Therapy Determinated by Investigator

    Reporting group title
    cUTI:CAZ-AVI
    Reporting group description
    cUTI: CAZ-AVI

    Reporting group values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI Total
    Number of subjects
    15 12 153 153 333
    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)
    7 10 79 63 159
        From 65-84 years
    7 2 71 83 163
        85 years and over
    1 0 3 7 11
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    59.5 ± 18.78 50.3 ± 14.71 61 ± 15.27 64.3 ± 14.72 -
    Gender, Male/Female
    Units: Participants
        Female
    5 7 73 67 152
        Male
    10 5 80 86 181
    Age, Customized
    Units: Subjects
        18-45
    3 3 24 20 50
        46-64
    4 7 55 43 109
        65-74
    4 2 46 50 102
        75-90
    4 0 28 40 72

    End points

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    End points reporting groups
    Reporting group title
    cIAI:Best Available Therapy
    Reporting group description
    cIAI: Best Available Therapy Determinated by Investigator

    Reporting group title
    cIAI:CAZ-AVI + metronidazole
    Reporting group description
    cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)

    Reporting group title
    cUTI:Best Available Therapy
    Reporting group description
    cUTI:Best Available Therapy Determinated by Investigator

    Reporting group title
    cUTI:CAZ-AVI
    Reporting group description
    cUTI: CAZ-AVI

    Primary: Clinical response at Test of Cure (TOC) in Microbiological modified intent-to-treat (mMITT) analysis set

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    End point title
    Clinical response at Test of Cure (TOC) in Microbiological modified intent-to-treat (mMITT) analysis set [1]
    End point description
    Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Primary
    End point timeframe
    6-12 days after last infusion of study therapy
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Clinical cure
    6
    8
    129
    132
        Clinical failure
    0
    0
    2
    2
        Indeterminate
    5
    2
    6
    10
    No statistical analyses for this end point

    Secondary: Clinical response at End of treatment (EOT) in mMITT analysis set.

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    End point title
    Clinical response at End of treatment (EOT) in mMITT analysis set.
    End point description
    Proportion of patients with clinical cure at the EOT visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Clinical cure
    6
    9
    136
    142
        Clinical failure
    0
    0
    0
    0
        Indeterminate
    5
    1
    1
    2
    No statistical analyses for this end point

    Secondary: Clinical response at Follow-up 1 (FU1) in mMITT analysis set

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    End point title
    Clinical response at Follow-up 1 (FU1) in mMITT analysis set
    End point description
    Proportion of patients with clinical cure at the FU1 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Clinical cure
    6
    8
    121
    127
        Clinical failure
    0
    0
    8
    5
        Indeterminate
    5
    2
    8
    12
    No statistical analyses for this end point

    Secondary: Clinical response at Follow-up 2 (FU2) in mMITT analysis set

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    End point title
    Clinical response at Follow-up 2 (FU2) in mMITT analysis set
    End point description
    Proportion of patients with clinical cure at the FU2 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [2]
    0 [3]
    137
    144
    Units: Participant
        Clinical cure
    118
    123
        Clinical failure
    13
    11
        Indeterminate
    6
    10
    Notes
    [2] - cIAI patients: FU2 is not applicable.
    [3] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Clinical response at EOT in Extended Microbiologically Evaluable (EME) at EOT analysis set.

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    End point title
    Clinical response at EOT in Extended Microbiologically Evaluable (EME) at EOT analysis set.
    End point description
    Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    9
    127
    134
    Units: Participant
        Clinical cure
    5
    9
    127
    134
        Clinical failure
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Clinical response at TOC in EME at TOC analysis set.

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    End point title
    Clinical response at TOC in EME at TOC analysis set.
    End point description
    Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    122
    128
    Units: Participant
        Clinical cure
    5
    8
    120
    126
        Clinical failure
    0
    0
    2
    2
    No statistical analyses for this end point

    Secondary: Clinical response at FU1 in EME at FU1 analysis set.

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    End point title
    Clinical response at FU1 in EME at FU1 analysis set.
    End point description
    Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    7
    118
    124
    Units: Participant
        Clinical cure
    5
    7
    110
    120
        Clinical failure
    0
    0
    8
    4
    No statistical analyses for this end point

    Secondary: Clinical response at FU2 in EME at FU2 analysis set

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    End point title
    Clinical response at FU2 in EME at FU2 analysis set
    End point description
    Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [4]
    0 [5]
    114
    116
    Units: Participant
        Clinical cure
    102
    106
        Clinical failure
    12
    10
    Notes
    [4] - cIAI patients: FU2 is not applicable.
    [5] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Clinical cure at TOC by baseline Gram-negative pathogen in mMITT analysis set

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    End point title
    Clinical cure at TOC by baseline Gram-negative pathogen in mMITT analysis set
    End point description
    Proportion of patients with clinical cure at TOC visit by baseline pathogen (>=10% of frequncy in the combined cIAI and cUTI patients) in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        E. coli - Clinical cure (n=6, 4, 57, 59)
    2
    3
    54
    53
        K. pneumoniae - Clinical cure (n=3, 5, 65, 55)
    2
    3
    61
    54
        P. aeruginosa - clinical cure (n=1, 1, 5, 14)
    1
    1
    5
    12
    No statistical analyses for this end point

    Secondary: Clinical cure at TOC by baseline Gram-negative pathogen in EME at TOC analysis set

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    End point title
    Clinical cure at TOC by baseline Gram-negative pathogen in EME at TOC analysis set
    End point description
    Proportion of patients with clinical cure at TOC visit by baseline Gram-negative pathogen (>=10% of frequncy in the combined cIAI and cUTI patients) in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    124
    131
    Units: Participant
        E. coli - Clinical cure (n=2, 3, 48, 52)
    2
    3
    47
    51
        K. pneumoniae - Clinical cure (n=2, 3, 59, 53)
    2
    3
    59
    53
        P. aeruginosa - Clinical cure (n=1, 1, 5, 12)
    1
    1
    5
    12
    No statistical analyses for this end point

    Secondary: Clinical cure at TOC by previously failed treatment class in mMITT analysis set

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    End point title
    Clinical cure at TOC by previously failed treatment class in mMITT analysis set
    End point description
    Proportion of patients with clinical cure at TOC visit by previously failed treatment class in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        At least 1 failed - Cure (n=4,7,12,7)
    3
    7
    12
    6
        Antibiotics - Cure (n=0,1,0,0)
    0
    1
    0
    0
        Carbapenems - Cure (n=1,0,1,2)
    0
    0
    1
    1
        Comb of Sulf/Trime inc Deriv-Cure(n=0,0,2,0)
    0
    0
    2
    0
        Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)
    1
    3
    0
    2
        Cortico,Po. Comb W/Antibio.-Cure(n=0,0,1,0)
    0
    0
    1
    0
        First-Gen. Cephalosporins-Cure (n=0,0,2,0)
    0
    0
    2
    0
        Fluoroquinolones - Cure (n=1,2,7,1)
    0
    2
    7
    1
        Glycopeptide Antibacterials-Cure (n=1,0,0,0)
    0
    0
    0
    0
        Imidazole Derivatives - Cure (n=2,3,0,0)
    1
    3
    0
    0
        Other Aminoglycosides-Cure (n=0,0,1,1)
    0
    0
    1
    1
        Other Antibacterials-Cure (n=0,1,1,0)
    0
    1
    1
    0
        Other Antibio. F. Topic. Use-Cure(n=0,0,1,0)
    0
    0
    1
    0
        Penici. With Ext. Spectrum-Cure(n=0,1,0,0)
    0
    1
    0
    0
        Third-Gen.Cephalosporins -Cure(n=2,4,3,2)
    2
    4
    3
    2
    No statistical analyses for this end point

    Secondary: Clinical cure at EOT by previously failed treatment class in EME at EOT analysis set

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    End point title
    Clinical cure at EOT by previously failed treatment class in EME at EOT analysis set
    End point description
    Proportion of patients with clinical cure at EOT visit by previously failed treatment class in EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    9
    127
    134
    Units: Participant
        Antibiotics - Cure (n=0,1,0,0)
    0
    1
    0
    0
        Carbapenems - Cure (n=0,0,1,1)
    0
    0
    1
    1
        Comb of Sulf/Trime inc Deriv-Cure(n=0,0,2,0)
    0
    0
    2
    0
        Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)
    1
    3
    0
    2
        Cortico,Po. Comb W/Antibio.-Cure(n=0,0,1,0)
    0
    0
    1
    0
        First-Gen. Cephalosporins-Cure (n=0,0,2,0)
    0
    0
    2
    0
        Fluoroquinolones - Cure (n=0,2,5,1)
    0
    2
    5
    1
        Imidazole Derivatives - Cure (n=1,3,0,0)
    1
    3
    0
    0
        Other Aminoglycosides-Cure (n=0,0,1,1)
    0
    0
    1
    1
        Other Antibacterials-Cure (n=0,1,1,0)
    0
    1
    1
    0
        Other Antibio. F. Topic. Use-Cure(n=0,0,1,0)
    0
    0
    1
    0
        Penici. With Ext. Spectrum-Cure(n=0,1,0,0)
    0
    1
    0
    0
        Third-Gen.Cephalosporins -Cure(n=2,4,2,2)
    2
    4
    2
    2
    No statistical analyses for this end point

    Secondary: Clinical cure at TOC by previously failed treatment class in EME at TOC analysis set

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    End point title
    Clinical cure at TOC by previously failed treatment class in EME at TOC analysis set
    End point description
    Proportion of patients with clinical cure at TOC visit by previously failed treatment class in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    122
    128
    Units: Participant
        Antibiotics - Cure (n=0,1,0,0)
    0
    1
    0
    0
        Carbapenems - Cure (n=0,0,1,1)
    0
    0
    1
    1
        Comb of Sulf/Trime inc Deriv-Cure(n=0,0,2,0)
    0
    0
    2
    0
        Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)
    1
    3
    0
    2
        Cortico,Po. Comb W/Antibio.-Cure(n=0,0,1,0)
    0
    0
    1
    0
        First-Gen. Cephalosporins-Cure (n=0,0,2,0)
    0
    0
    2
    0
        Fluoroquinolones - Cure (n=0,2,5,1)
    0
    2
    5
    1
        Imidazole Derivatives - Cure (n=1,3,0,0)
    1
    3
    0
    0
        Other Aminoglycosides-Cure (n=0,0,0,1)
    0
    0
    0
    1
        Other Antibacterials-Cure (n=0,1,1,0)
    0
    1
    1
    0
        Other Antibio. F. Topic. Use-Cure(n=0,0,1,0)
    0
    0
    1
    0
        Penici. With Ext. Spectrum-Cure(n=0,1,0,0)
    0
    1
    0
    0
        Third-Gen.Cephalosporins -Cure(n=2,4,2,2)
    2
    4
    2
    2
    No statistical analyses for this end point

    Secondary: Clinical cure at FU1 by previously failed treatment class in EME at FU1 analysis set

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    End point title
    Clinical cure at FU1 by previously failed treatment class in EME at FU1 analysis set
    End point description
    Proportion of patients with clinical cure at FU1 visit by previously failed treatment class in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
    End point type
    Secondary
    End point timeframe
    cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    7
    118
    124
    Units: Participant
        Antibiotics - Cure (n=0,1,0,0)
    0
    1
    0
    0
        Carbapenems - Cure (n=0,0,1,1)
    0
    0
    1
    1
        Comb of Sulf/Trime inc Deriv-Cure(n=0,0,1,0)
    0
    0
    1
    0
        Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)
    1
    3
    0
    2
        Cortico,Po. Comb W/Antibio.-Cure(n=0,0,1,0)
    0
    0
    0
    0
        First-Gen. Cephalosporins-Cure (n=0,0,2,0)
    0
    0
    2
    0
        Fluoroquinolones - Cure (n=0,2,5,1)
    0
    2
    4
    1
        Imidazole Derivatives - Cure (n=1,3,0,0)
    1
    3
    0
    0
        Other Aminoglycosides-Cure (n=0,0,0,1)
    0
    0
    0
    1
        Other Antibacterials-Cure (n=0,1,1,0)
    0
    1
    1
    0
        Other Antibio. F. Topic. Use-Cure(n=0,0,1,0)
    0
    0
    1
    0
        Penici. With Ext. Spectrum-Cure(n=0,1,0,0)
    0
    1
    0
    0
        Third-Gen.Cephalosporins -Cure(n=2,4,1,2)
    2
    4
    0
    2
    No statistical analyses for this end point

    Secondary: Clinical cure at FU2 by previously failed treatment class in EME at FU2 analysis set

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    End point title
    Clinical cure at FU2 by previously failed treatment class in EME at FU2 analysis set
    End point description
    Proportion of patients with clinical cure at FU2 visit by previously failed treatment class in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [6]
    0 [7]
    114
    116
    Units: Participant
        Carbapenems - Cure (n=1,0)
    0
    0
        Comb of Sulf/Trime inc Deriv-Cure(n=1,0)
    0
    0
        Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=0,2)
    0
    2
        Cortico,Po. Comb W/Antibio.-Cure(n=1,0)
    0
    0
        First-Gen. Cephalosporins-Cure (n=2,0)
    2
    0
        Fluoroquinolones - Cure (n=5,0)
    4
    0
        Other Aminoglycosides-Cure (n=0,1)
    0
    1
        Other Antibacterials-Cure (n=1,0)
    0
    0
        Other Antibio. F. Topic. Use-Cure(n=1,0)
    1
    0
        Third-Gen.Cephalosporins -Cure(n=1,1)
    0
    1
    Notes
    [6] - cIAI patients: FU2 is not applicable.
    [7] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at EOT in mMITT analysis set

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    End point title
    Per-patient microbiological response at EOT in mMITT analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Favorable
    6
    9
    130
    136
        Unfavorable
    0
    0
    1
    1
        Indeterminate
    5
    1
    6
    7
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at TOC in mMITT analysis set

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    End point title
    Per-patient microbiological response at TOC in mMITT analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Favorable
    6
    8
    88
    118
        Unfavorable
    0
    0
    42
    17
        Indeterminate
    5
    2
    7
    9
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at FU1 in mMITT analysis set

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    End point title
    Per-patient microbiological response at FU1 in mMITT analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Favorable
    6
    8
    78
    103
        Unfavorable
    0
    0
    50
    29
        Indeterminate
    5
    2
    9
    12
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at FU2 in mMITT analysis set

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    End point title
    Per-patient microbiological response at FU2 in mMITT analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [8]
    0 [9]
    137
    144
    Units: Participant
        Favorable
    73
    99
        Unfavorable
    54
    35
        Indeterminate
    10
    10
    Notes
    [8] - cIAI patients: FU2 is not applicable.
    [9] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at EOT in EME at EOT analysis set

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    End point title
    Per-patient microbiological response at EOT in EME at EOT analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    9
    127
    134
    Units: Participant
        Favorable
    5
    9
    127
    133
        Unfavorable
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at TOC in EME at TOC analysis set

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    End point title
    Per-patient microbiological response at TOC in EME at TOC analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    124
    131
    Units: Participant
        Favorable
    5
    8
    84
    114
        Unfavorable
    0
    0
    40
    17
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at FU1 in EME at FU1 analysis set

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    End point title
    Per-patient microbiological response at FU1 in EME at FU1 analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    7
    120
    126
    Units: Participant
        Favorable
    5
    7
    75
    98
        Unfavorable
    0
    0
    45
    28
    No statistical analyses for this end point

    Secondary: Per-patient microbiological response at FU2 in EME at FU2 analysis set

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    End point title
    Per-patient microbiological response at FU2 in EME at FU2 analysis set
    End point description
    Microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [10]
    0 [11]
    115
    117
    Units: Participant
        Favorable
    68
    85
        Unfavorable
    47
    32
    Notes
    [10] - cIAI patients: FU2 is not applicable.
    [11] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at EOT in mMITT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at EOT in mMITT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        E. coli - Favorable (n=6, 4, 57, 59)
    2
    3
    53
    57
        E. coli - Unfavorable (n=6, 4, 57, 59)
    0
    0
    0
    0
        E. coli - Indeterminate (n=6, 4, 57, 59)
    4
    1
    4
    2
        K. pneumoniae - Favorable (n=3, 5, 65, 55)
    2
    4
    61
    52
        K. pneumoniae - Unfavorable (n=3, 5, 65, 55)
    0
    0
    1
    0
        K. pneumoniae - Indeterminate (n=3, 5, 65, 55)
    1
    1
    3
    3
        P. aeruginosa - Favorable (n=1, 1, 5, 14)
    1
    1
    5
    14
        P. aeruginosa - Unfavorable (n=1, 1, 5, 14)
    0
    0
    0
    0
        P. aeruginosa - Indeterminate (n=1, 1, 5, 14)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at TOC in mMITT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at TOC in mMITT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        E. coli - Favorable (n=6, 4, 57, 59)
    2
    3
    38
    52
        E. coli - Unfavorable (n=6, 4, 57, 59)
    0
    0
    16
    3
        E. coli - Indeterminate (n=6, 4, 57, 59)
    4
    1
    3
    4
        K. pneumoniae - Favorable (n=3, 5, 65, 55)
    2
    3
    43
    46
        K. pneumoniae - Unfavorable (n=3, 5, 65, 55)
    0
    0
    19
    8
        K. pneumoniae - Indeterminate (n=3, 5, 65, 55)
    1
    2
    3
    1
        P. aeruginosa - Favorable (n=1, 1, 5, 14)
    1
    1
    3
    11
        P. aeruginosa - Unfavorable (n=1, 1, 5, 14)
    0
    0
    2
    2
        P. aeruginosa - Indeterminate (n=1, 1, 5, 14)
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at FU1 in mMITT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at FU1 in mMITT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        E. coli - Favorable (n=6, 4, 57, 59)
    2
    3
    33
    45
        E. coli - Unfavorable (n=6, 4, 57, 59)
    0
    0
    18
    12
        E. coli - Indeterminate (n=6, 4, 57, 59)
    4
    1
    6
    2
        K. pneumoniae - Favorable (n=3, 5, 65, 55)
    2
    3
    39
    42
        K. pneumoniae - Unfavorable (n=3, 5, 65, 55)
    0
    0
    23
    10
        K. pneumoniae - Indeterminate (n=3, 5, 65, 55)
    1
    2
    3
    3
        P. aeruginosa - Favorable (n=1, 1, 5, 14)
    1
    1
    3
    8
        P. aeruginosa - Unfavorable (n=1, 1, 5, 14)
    0
    0
    2
    2
        P. aeruginosa - Indeterminate (n=1, 1, 5, 14)
    0
    0
    0
    4
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at FU2 in mMITT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at FU2 in mMITT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [12]
    0 [13]
    137
    144
    Units: Participant
        E. coli - Favorable (n=0, 0, 57, 59)
    32
    43
        E. coli - Unfavorable (n=0, 0, 57, 59)
    19
    14
        E. coli - Indeterminate (n=0, 0, 57, 59)
    6
    2
        K. pneumoniae - Favorable (n=0, 0, 65, 55)
    35
    39
        K. pneumoniae - Unfavorable (n=0, 0, 65, 55)
    26
    14
        K. pneumoniae - Indeterminate (n=0, 0, 65, 55)
    4
    2
        P. aeruginosa - Favorable (n=0, 0, 5, 14)
    2
    10
        P. aeruginosa - Unfavorable (n=0, 0, 5, 14)
    3
    2
        P. aeruginosa - Indeterminate (n=0, 0, 5, 14)
    0
    2
    Notes
    [12] - cIAI patients: FU2 is not applicable.
    [13] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at EOT in EME at EOT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at EOT in EME at EOT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    28 hours after completion of last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    9
    127
    134
    Units: Participant
        E. coli - Favorable (n=2, 3, 51, 55)
    2
    3
    51
    55
        E. coli - Unfavorable (n=2, 3, 51, 55)
    0
    0
    0
    0
        K. pneumoniae - Favorable (n=2, 4, 60, 52)
    2
    4
    60
    52
        K. pneumoniae - Unfavorable (n=2, 4, 60, 52)
    0
    0
    0
    0
        P. aeruginosa - Favorable (n=1, 1, 5, 14)
    1
    1
    5
    14
        P. aeruginosa - Unfavorable (n=1, 1, 5, 14)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at TOC in EME at TOC analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at TOC in EME at TOC analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    124
    131
    Units: Participant
        E. coli - Favorable (n=2, 3, 49, 53)
    2
    3
    34
    50
        E. coli - Unfavorable (n=2, 3, 49, 53)
    0
    0
    15
    3
        K. pneumoniae - Favorable (n=2, 3, 60, 53)
    2
    3
    42
    45
        K. pneumoniae - Unfavorable (n=2, 3, 60, 53)
    0
    0
    18
    8
        P. aeruginosa - Favorable (n=1, 1, 5, 13)
    1
    1
    3
    11
        P. aeruginosa - Unfavorable (n=1, 1, 5, 13)
    0
    0
    2
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at FU1 in EME at FU1 analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at FU1 in EME at FU1 analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    7
    120
    126
    Units: Participant
        E. coli - Favorable (n=2, 3, 46, 54)
    2
    3
    30
    43
        E. coli - Unfavorable (n=2, 3, 46, 54)
    0
    0
    16
    11
        K. pneumoniae - Favorable (n=2, 2, 59, 50)
    2
    2
    38
    40
        K. pneumoniae - Unfavorable (n=2, 2, 59, 50)
    0
    0
    21
    10
        P. aeruginosa - Favorable (n=1, 1, 5, 10)
    1
    1
    3
    8
        P. aeruginosa - Unfavorable (n=1, 1, 5, 10)
    0
    0
    2
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at FU2 in EME at FU2 analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at FU2 in EME at FU2 analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    cUTI only: 28-34 calendar days from randomization
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    0 [14]
    0 [15]
    115
    117
    Units: Participant
        E. coli - Favorable (n=44, 50)
    28
    39
        E. coli - Unfavorable (n=44, 50)
    16
    11
        K. pneumoniae - Favorable (n= 56, 46)
    33
    32
        K. pneumoniae - Unfavorable (n=56, 46)
    23
    14
        P. aeruginosa - Favorable (n=4, 11)
    2
    9
        P. aeruginosa - Unfavorable (n=4, 11)
    2
    2
    Notes
    [14] - cIAI patients: FU2 is not applicable.
    [15] - cIAI patients: FU2 is not applicable.
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at TOC by CAZ-AVI MIC in mMITT analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at TOC by CAZ-AVI MIC in mMITT analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        E. coli (MIC: <=0.008)-Favorable (n=0, 0, 1, 1)
    0
    0
    1
    1
        E. coli (MIC: 0.03)-Favorable (n=0, 0, 0, 2)
    0
    0
    0
    1
        E. coli (MIC: 0.06)-Favorable (n=1, 0, 3, 2)
    0
    0
    3
    2
        E. coli (MIC: 0.12)-Favorable (n=4, 2, 20, 20)
    2
    1
    12
    16
        E. coli (MIC: 0.25)-Favorable (n=0, 0, 15, 16)
    0
    0
    10
    15
        E. coli (MIC: 0.5)-Favorable (n=0, 1, 8, 11)
    0
    1
    5
    10
        E. coli (MIC: 1)-Favorable (n=0, 0, 2, 2)
    0
    0
    1
    2
        E. coli (MIC: 2)-Favorable (n=0, 0, 2, 1)
    0
    0
    2
    1
        E. coli (MIC: 8)-Favorable (n=0, 0, 2, 4)
    0
    0
    2
    4
        K. pneumoniae (MIC: 0.06)-Favorable (n=0,0,2,0)
    0
    0
    1
    0
        K. pneumoniae (MIC: 0.12)-Favorable (n=0,1,8,5)
    0
    0
    6
    4
        K. pneumoniae (MIC: 0.25)-Favorable (n=0,3,12,6)
    0
    2
    7
    5
        K. pneumoniae (MIC: 0.5)-Favorable (n=2,0,24,22)
    1
    0
    16
    19
        K. pneumoniae (MIC: 1)-Favorable (n=0,0,16,18)
    0
    0
    11
    16
        K. pneumoniae (MIC: 2)-Favorable (n=1, 1, 1, 2)
    1
    1
    1
    1
        K. pneumoniae (MIC: 4)-Favorable (n=0, 0, 1, 1)
    0
    0
    1
    0
        K. pneumoniae (MIC: 32)-Favorable (n=0, 0, 1, 0)
    0
    0
    0
    0
        K. pneumoniae (MIC: >32)-Favorable (n=0,0,0,1)
    0
    0
    0
    0
        P. aeruginosa (MIC: 2)-Favorable (n=1, 0, 0, 1)
    1
    0
    0
    1
        P. aeruginosa (MIC: 4)-Favorable (n=0, 0, 3, 2)
    0
    0
    1
    1
        P. aeruginosa (MIC: 8)-Favorable (n=0, 0, 0, 2)
    0
    0
    0
    2
        P. aeruginosa (MIC: 16)-Favorable (n=0, 1, 0, 1)
    0
    1
    0
    0
        P. aeruginosa (MIC: 32)-Favorable (n=0, 0, 1, 3)
    0
    0
    1
    3
        P. aeruginosa (MIC: >32)-Favorable (n=0,0,1,5)
    0
    0
    1
    4
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response of Gram-negative pathogen at TOC by CAZ-AVI MIC in EME at TOC analysis set

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    End point title
    Per-pathogen microbiological response of Gram-negative pathogen at TOC by CAZ-AVI MIC in EME at TOC analysis set
    End point description
    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification &lt; 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
    End point type
    Secondary
    End point timeframe
    6-12 days after last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    124
    131
    Units: Participant
        E. coli (MIC: <=0.008)-Favorable (n=0, 0, 1, 1)
    0
    0
    1
    1
        E. coli (MIC: 0.03)-Favorable (n=0, 0, 0, 2)
    0
    0
    0
    1
        E. coli (MIC: 0.06)-Favorable (n=0, 0, 3, 1)
    0
    0
    3
    1
        E. coli (MIC: 0.12)-Favorable (n=2, 1, 18, 18)
    2
    1
    10
    16
        E. coli (MIC: 0.25)-Favorable (n=0, 0, 13, 15)
    0
    0
    9
    15
        E. coli (MIC: 0.5)-Favorable (n=0, 1, 6, 9)
    0
    1
    4
    9
        E. coli (MIC: 1)-Favorable (n=0, 0, 2, 2)
    0
    0
    1
    2
        E. coli (MIC: 2)-Favorable (n=0, 0, 2, 1)
    0
    0
    2
    1
        E. coli (MIC: 8)-Favorable (n=0, 0, 2, 4)
    0
    0
    2
    4
        K. pneumoniae (MIC: 0.06)-Favorable (n=0,0,1,0)
    0
    0
    0
    0
        K. pneumoniae (MIC: 0.12)-Favorable (n=0,0,8,5)
    0
    0
    6
    4
        K. pneumoniae (MIC: 0.25)-Favorable (n=0,2,11,6)
    0
    2
    7
    5
        K. pneumoniae (MIC: 0.5)-Favorable (n=1,0,23,21)
    1
    0
    16
    19
        K. pneumoniae (MIC: 1)-Favorable (n=0,0,15,17)
    0
    0
    11
    15
        K. pneumoniae (MIC: 2)-Favorable (n=1, 1, 1, 2)
    1
    1
    1
    2
        K. pneumoniae (MIC: 4)-Favorable (n=0, 0, 1, 1)
    0
    0
    1
    0
        K. pneumoniae (MIC: >32)-Favorable (n=0,0,0,1)
    0
    0
    0
    0
        P. aeruginosa (MIC: 2)-Favorable (n=1, 0, 0, 1)
    1
    0
    0
    1
        P. aeruginosa (MIC: 4)-Favorable (n=0, 0, 3, 2)
    0
    0
    1
    1
        P. aeruginosa (MIC: 8)-Favorable (n=0, 0, 0, 2)
    0
    0
    0
    2
        P. aeruginosa (MIC: 16)-Favorable (n=0, 1, 0, 1)
    0
    1
    0
    0
        P. aeruginosa (MIC: 32)-Favorable (n=0, 0, 1, 3)
    0
    0
    1
    3
        P. aeruginosa (MIC: >32)-Favorable (n=0,0,1,4)
    0
    0
    1
    4
    No statistical analyses for this end point

    Secondary: The reason for treatment change/discontinuation in mMITT analysis set

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    End point title
    The reason for treatment change/discontinuation in mMITT analysis set
    End point description
    Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted.
    End point type
    Secondary
    End point timeframe
    From first infusion to last infusion of study therapy
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        Treatment Change
    1
    0
    8
    11
        Treatment Change - Crcl change
    1
    0
    5
    10
        Treatment Change - Other
    0
    0
    3
    1
        Treatment discontinuation
    4
    0
    3
    1
        Treatment discontinuation - AE
    1
    0
    1
    1
        Treatment discontinuation - Other
    3
    0
    2
    0
        Treatment interrupted
    0
    0
    0
    1
        Treatment interrupted - Change of infusion site
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: The 28 days all cause mortality rate in mMITT analysis set

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    End point title
    The 28 days all cause mortality rate in mMITT analysis set
    End point description
    Proportion of patients with Day 28 all-cause mortality in mMITT analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
    End point type
    Secondary
    End point timeframe
    From first infusion to Day 28
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    11
    10
    137
    144
    Units: Participant
        All cause mortality
    1
    0
    3
    3
        Deaths due to disease progression
    0
    0
    0
    0
        Number of patients with any AE with outcome=death
    1
    0
    3
    3
    No statistical analyses for this end point

    Secondary: The 28 days all cause mortality rate in EME at TOC analysis set

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    End point title
    The 28 days all cause mortality rate in EME at TOC analysis set
    End point description
    Proportion of patients with Day 28 all-cause mortality in EME at TOC analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
    End point type
    Secondary
    End point timeframe
    From first infusion to Day 28
    End point values
    cIAI:Best Available Therapy cIAI:CAZ-AVI + metronidazole cUTI:Best Available Therapy cUTI:CAZ-AVI
    Number of subjects analysed
    5
    8
    124
    131
    Units: Participant
        All cause mortality
    0
    0
    1
    1
        Deaths due to disease progression
    0
    0
    0
    0
        Number of patients with any AE withoutcome=death
    0
    0
    1
    1
    No statistical analyses for this end point

    Secondary: Plasma concentrations for ceftazidime (CAZ) within 15 minutes before/ after dose in PK analysis set

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    End point title
    Plasma concentrations for ceftazidime (CAZ) within 15 minutes before/ after dose in PK analysis set [16]
    End point description
    Blood samples were taken at anytime within 15 minutes prior to or after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    Anytime within 15 minutes prior to or after stopping study drug
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    145
    Units: NG/ML
        geometric mean (full range (min-max))
    23880.3 (2700 to 80900)
    74260.2 (5970 to 1640000)
    No statistical analyses for this end point

    Secondary: Plasma concentrations for avibactam (AVI) within 15 minutes before/ after study dose in PK analysis set

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    End point title
    Plasma concentrations for avibactam (AVI) within 15 minutes before/ after study dose in PK analysis set [17]
    End point description
    Blood samples were taken at anytime within 15 minutes prior to or after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    Anytime within 15 minutes prior to or after stopping study drug
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    147
    Units: NG/ML
        geometric mean (full range (min-max))
    3061.3 (286 to 13200)
    10103.8 (504 to 376000)
    No statistical analyses for this end point

    Secondary: Plasma concentrations for ceftazidime (CAZ) between 30 to 90 minutes after dose in PK analysis set

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    End point title
    Plasma concentrations for ceftazidime (CAZ) between 30 to 90 minutes after dose in PK analysis set [18]
    End point description
    Blood samples were taken at anytime between 30 to 90 minutes after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    anytime between 30 to 90 minutes after stopping study drug
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    141
    Units: NG/ML
        geometric mean (full range (min-max))
    39465.3 (2620 to 85500)
    56905.9 (14700 to 1910000)
    No statistical analyses for this end point

    Secondary: Plasma concentrations for avibactam (AVI) between 30 to 90 minutes after dose in PK analysis set

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    End point title
    Plasma concentrations for avibactam (AVI) between 30 to 90 minutes after dose in PK analysis set [19]
    End point description
    Blood samples were taken at anytime between 30 to 90 minutes after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    anytime between 30 to 90 minutes after stopping study drug
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    147
    Units: NG/ML
        geometric mean (full range (min-max))
    6304.1 (285 to 15500)
    8141.2 (773 to 405000)
    No statistical analyses for this end point

    Secondary: Plasma concentrations for ceftazidime (CAZ) between 300 to 360 minutes after dose in PK analysis set

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    End point title
    Plasma concentrations for ceftazidime (CAZ) between 300 to 360 minutes after dose in PK analysis set [20]
    End point description
    Blood samples were taken at anytime between 300 to 360 minutes after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    anytime between 300 to 360 minutes after stopping study drug
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    146
    Units: NG/ML
        geometric mean (full range (min-max))
    14904.8 (2500 to 58100)
    21442 (2490 to 1600000)
    No statistical analyses for this end point

    Secondary: Plasma concentrations for avibactam (AVI) between 300 to 360 minutes after dose in PK analysis set

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    End point title
    Plasma concentrations for avibactam (AVI) between 300 to 360 minutes after dose in PK analysis set [21]
    End point description
    Blood samples were taken at anytime between 300 to 360 minutes after stopping study drug on Day 3 for ceftazidime and avibactam plasma concentration.
    End point type
    Secondary
    End point timeframe
    anytime between 300 to 360 minutes after stopping study drug
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No treatment comparisons were done in this study. No no statistical analysis section were entered.
    End point values
    cIAI:CAZ-AVI + metronidazole cUTI:CAZ-AVI
    Number of subjects analysed
    12
    146
    Units: NG/ML
        geometric mean (full range (min-max))
    1769.3 (277 to 7900)
    2425 (315 to 431000)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non serious AEs and SAEs were from the first infusion of study therapy through the FU visits (cIAI: 28-35 days calendar days from randomization, cUTI: 28-32 calendar days from randomization).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    cIAI:Best Available Therapy
    Reporting group description
    cIAI: Best Available Therapy Determinated by Investigator

    Reporting group title
    cUTI:Best Available Therapy
    Reporting group description
    cUTI:Best Available Therapy Determinated by Investigator

    Reporting group title
    cUTI:CAZ-AVI
    Reporting group description
    cUTI: CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)

    Reporting group title
    cIAI:CAZ-AVI + metronidazole
    Reporting group description
    cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)

    Serious adverse events
    cIAI:Best Available Therapy cUTI:Best Available Therapy cUTI:CAZ-AVI cIAI:CAZ-AVI + metronidazole
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 15 (33.33%)
    5 / 153 (3.27%)
    7 / 152 (4.61%)
    2 / 12 (16.67%)
         number of deaths (all causes)
    1
    3
    3
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Injury, poisoning and procedural complications
    Pancreatic injury
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         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 fistula
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Cardiac arrest
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 153 (1.31%)
    1 / 152 (0.66%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Pneumonia aspiration
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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 embolism
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Respiratory failure
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (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
    Nervous system disorders
    Presyncope
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Asthenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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 disorders
    Intestinal obstruction
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Hernial eventration
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (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
    Nausea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Small intestinal perforation
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         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
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Infections and infestations
    Urosepsis
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (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
    Lobar pneumonia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (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
    Pneumonia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (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
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (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
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    cIAI:Best Available Therapy cUTI:Best Available Therapy cUTI:CAZ-AVI cIAI:CAZ-AVI + metronidazole
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 15 (80.00%)
    36 / 153 (23.53%)
    18 / 152 (11.84%)
    8 / 12 (66.67%)
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 153 (1.31%)
    1 / 152 (0.66%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    1
    2
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperthermia
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 153 (1.31%)
    4 / 152 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    3
    8
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    4 / 15 (26.67%)
    0 / 153 (0.00%)
    2 / 152 (1.32%)
    2 / 12 (16.67%)
         occurrences all number
    4
    0
    2
    2
    Injury, poisoning and procedural complications
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 153 (1.31%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Endoscopy gastrointestinal abnormal
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    1
    2
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Atelectasis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hydrothorax
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Tachypnoea
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Nervous system disorders
    Hydrocephalus
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Parosmia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    1 / 152 (0.66%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    1
    Headache
         subjects affected / exposed
    1 / 15 (6.67%)
    11 / 153 (7.19%)
    1 / 152 (0.66%)
    2 / 12 (16.67%)
         occurrences all number
    1
    17
    1
    2
    Paraesthesia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    2 / 152 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Abdominal pain
         subjects affected / exposed
    1 / 15 (6.67%)
    4 / 153 (2.61%)
    3 / 152 (1.97%)
    0 / 12 (0.00%)
         occurrences all number
    4
    5
    3
    0
    Diarrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    8 / 153 (5.23%)
    3 / 152 (1.97%)
    2 / 12 (16.67%)
         occurrences all number
    0
    8
    4
    2
    Duodenitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 15 (0.00%)
    5 / 153 (3.27%)
    2 / 152 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    5
    2
    0
    Enteritis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Pancreatitis acute
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Oesophagitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Gastritis erosive
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 153 (1.31%)
    4 / 152 (2.63%)
    2 / 12 (16.67%)
         occurrences all number
    1
    2
    5
    2
    Nausea
         subjects affected / exposed
    1 / 15 (6.67%)
    9 / 153 (5.88%)
    5 / 152 (3.29%)
    3 / 12 (25.00%)
         occurrences all number
    1
    9
    5
    3
    Renal and urinary disorders
    Nocturia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    2 / 152 (1.32%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    2
    1
    Urticaria
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 153 (0.65%)
    1 / 152 (0.66%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    1
    1
    Back pain
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Muscular weakness
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Bone pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    2 / 152 (1.32%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    1
    Neck pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 153 (0.65%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Metabolic acidosis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    1 / 152 (0.66%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Infections and infestations
    Incision site infection
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Oral herpes
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Orchitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 153 (0.00%)
    0 / 152 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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