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    Clinical Trial Results:
    A Phase III, Randomized, Multicenter, Double-Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime-Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram-Negative Pathogen in Hospitalized Adults

    Summary
    EudraCT number
    2011-005722-21
    Trial protocol
    GR   DE   CZ   ES   IT   BG   PL   GB  
    Global end of trial date
    21 Jul 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Feb 2016
    First version publication date
    05 Feb 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D4280C00004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    S-151 85, Södertälje, Sweden,
    Public contact
    Nel Moore, AstraZeneca AB, +44 7884115907, Nell.Moore@astrazeneca.com
    Scientific contact
    Leanne Gasink, AstraZeneca AB, +1 302-299-2237, 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
    04 Sep 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Aug 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the noninferiority of ceftazidime-avibactam (CAZ-AVI, formerly CAZ104) compared with doripenem with respect to the following FDA coprimary endpoints and EU primary endpoint in the microbiological modified intent-to-treat (mMITT) analysis set: FDA Primary Objective (Coprimary Endpoints): Symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) and resolution of, or improvement in, flank pain based on the patient-reported symptom assessment response at the Day 5 visit. Both per-patient favourable microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the Test of Cure (TOC) visit. EU Primary Objective: Per patient favourable microbiological response at the TOC visit.
    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
    10 Oct 2012
    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: 77
    Country: Number of subjects enrolled
    Croatia: 53
    Country: Number of subjects enrolled
    Czech Republic: 10
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Poland: 47
    Country: Number of subjects enrolled
    Romania: 154
    Country: Number of subjects enrolled
    Russian Federation: 184
    Country: Number of subjects enrolled
    Serbia: 8
    Country: Number of subjects enrolled
    Slovakia: 22
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    Ukraine: 215
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Portugal: 1
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    United States: 6
    Country: Number of subjects enrolled
    Argentina: 15
    Country: Number of subjects enrolled
    Brazil: 10
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Mexico: 29
    Country: Number of subjects enrolled
    Peru: 61
    Country: Number of subjects enrolled
    Taiwan: 14
    Country: Number of subjects enrolled
    Japan: 55
    Worldwide total number of subjects
    1033
    EEA total number of subjects
    409
    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)
    710
    From 65 to 84 years
    313
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 1033 patients were randomized in 133 centers in 25 countries. The first patient was randomized on 10OCT2012 and the last patient was randomized on 30JUN2014. A total of 5 patients in the CAZ-AVI arm and 8 patients in Doripenem arm were 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
    Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    CAZ-AVI
    Arm description
    Ceftazidime-avibactam treatment group
    Arm type
    Experimental

    Investigational medicinal product name
    Ceftazidime-avibactam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Sterile crystalline powder, 2000 mg ceftazidime and 500 mg avibactam

    Arm title
    Doripenem
    Arm description
    Doripenem treatment group
    Arm type
    Active comparator

    Investigational medicinal product name
    Doripenem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Sterile powder, 500 mg

    Number of subjects in period 1
    CAZ-AVI Doripenem
    Started
    516
    517
    Completed
    473
    476
    Not completed
    43
    41
         Other Eligibility criteria
    11
    9
         Consent withdrawn by subject
    12
    12
         Lost to follow-up
    20
    20

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    CAZ-AVI
    Reporting group description
    Ceftazidime-avibactam treatment group

    Reporting group title
    Doripenem
    Reporting group description
    Doripenem treatment group

    Reporting group values
    CAZ-AVI Doripenem Total
    Number of subjects
    516 517 1033
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    357 353 710
        From 65-84 years
    153 160 313
        85 years and over
    6 4 10
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    51.6 ± 19.82 52.3 ± 18.89 -
    Gender, Male/Female
    Units: Participants
        Female
    353 364 717
        Male
    163 153 316
    Age, Customized
    Units: Subjects
        18-45
    195 175 370
        46-64
    162 178 340
        65-74
    80 100 180
        75-90
    79 64 143

    End points

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    End points reporting groups
    Reporting group title
    CAZ-AVI
    Reporting group description
    Ceftazidime-avibactam treatment group

    Reporting group title
    Doripenem
    Reporting group description
    Doripenem treatment group

    Primary: Patient-reported symptomatic response at day 5 (mMITT analysis set): non-inferiority hypothesis test

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    End point title
    Patient-reported symptomatic response at day 5 (mMITT analysis set): non-inferiority hypothesis test
    End point description
    Proportion of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
    End point type
    Primary
    End point timeframe
    At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Symptomatic resolution
    276
    276
        Symptom persistence
    103
    124
        Indeterminate
    14
    17
        Symptomatic resolution rate
    70.2
    66.2
    Statistical analysis title
    Non-inferiority hypothesis test
    Statistical analysis description
    H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of symptomatic resolution rates ≤ -12.5%
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    [1]
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Difference of symp resolution rates
    Point estimate
    4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.39
         upper limit
    10.42
    Notes
    [1] - -12.5%

    Primary: Combined patient-reported symptomatic and microbiological response at TOC (mMITT analysis set): non-inferiority hypothesis test

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    End point title
    Combined patient-reported symptomatic and microbiological response at TOC (mMITT analysis set): non-inferiority hypothesis test
    End point description
    Proportion of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
    End point type
    Primary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Favorable
    280
    269
        Unfavorable
    81
    109
        Indeterminate
    32
    39
        Favorable response rate
    71.2
    64.5
    Statistical analysis title
    Non-inferiority hypothesis test
    Statistical analysis description
    H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable combined response rates ≤ -12.5%
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    [2]
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable combined resp rates
    Point estimate
    6.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3
         upper limit
    13.12
    Notes
    [2] - -12.5%

    Primary: Per-patient microbiological response at TOC (mMITT analysis set): non-inferiority hypothesis test

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    End point title
    Per-patient microbiological response at TOC (mMITT analysis set): non-inferiority hypothesis test
    End point description
    Proportion of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.
    End point type
    Primary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Favorable
    304
    296
        Unfavorable
    58
    83
        Indeterminate
    31
    38
        Favorable response rate
    77.4
    71
    Statistical analysis title
    Non-inferiority hypothesis test
    Statistical analysis description
    H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates ≤ -12.5%
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    [3]
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.33
         upper limit
    12.36
    Notes
    [3] - -12.5%

    Secondary: Per-patient microbiological response at EOT (IV) (mMITT analysis set)

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    End point title
    Per-patient microbiological response at EOT (IV) (mMITT analysis set)
    End point description
    Proportion of patients with a favorable per-patient microbiological response at EOT (IV)
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Favorable
    374
    395
        Unfavorable
    1
    3
        Indeterminate
    18
    19
        Favorable response rate
    95.2
    94.7
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    3.56

    Secondary: Per-patient microbiological response at LFU (mMITT analysis set)

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    End point title
    Per-patient microbiological response at LFU (mMITT analysis set)
    End point description
    Proportion of patients with a favorable per patient microbiological response at LFU
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Favorable
    268
    254
        Unfavorable
    83
    125
        Indeterminate
    42
    38
        Favorable response rate
    68.2
    60.9
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    7.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.68
         upper limit
    13.81

    Secondary: Per-patient microbiological response at EOT (IV) (ME at EOT (IV) analysis set)

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    End point title
    Per-patient microbiological response at EOT (IV) (ME at EOT (IV) analysis set)
    End point description
    Proportion of patients with a favorable per-patient microbiological response at EOT (IV)
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    325
    361
    Units: Participants
    number (not applicable)
        Favorable
    324
    359
        Unfavorable
    1
    2
        Favorable response rate
    99.7
    99.4
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    686
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.21
         upper limit
    1.72

    Secondary: Per-patient microbiological response at TOC (ME at TOC analysis set)

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    End point title
    Per-patient microbiological response at TOC (ME at TOC analysis set)
    End point description
    Proportion of patients with a favorable per patient microbiological response at TOC
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participants
    number (not applicable)
        Favorable
    241
    225
        Unfavorable
    45
    73
        Favorable response rate
    84.3
    75.5
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    584
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    8.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.27
         upper limit
    15.24

    Secondary: Per-patient microbiological response at LFU (ME at LFU analysis set)

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    End point title
    Per-patient microbiological response at LFU (ME at LFU analysis set)
    End point description
    Proportion of patients with a favorable per patient microbiological response at LFU
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    245
    262
    Units: Participants
    number (not applicable)
        Favorable
    182
    166
        Unfavorable
    63
    96
        Favorable response rate
    74.3
    63.4
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    507
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    10.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.86
         upper limit
    18.85

    Secondary: Per-patient microbiological response at EOT (IV) (Extended ME at EOT (IV) analysis set)

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    End point title
    Per-patient microbiological response at EOT (IV) (Extended ME at EOT (IV) analysis set)
    End point description
    Proportion of patients with a favorable per-patient microbiological response at EOT (IV)
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    336
    371
    Units: Participants
    number (not applicable)
        Favorable
    335
    369
        Favorable response rate
    99.7
    99.5
        Unfavorable
    1
    2
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.17
         upper limit
    1.68

    Secondary: Per-patient microbiological response at TOC (Extended ME at TOC analysis set)

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    End point title
    Per-patient microbiological response at TOC (Extended ME at TOC analysis set)
    End point description
    Proportion of patients with a favorable per patient microbiological response at TOC
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participants
    number (not applicable)
        Favorable
    243
    236
        Favorable response rate
    83.2
    75.9
        Unfavorable
    49
    75
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    603
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    7.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.88
         upper limit
    13.74

    Secondary: Per-patient microbiological response at LFU (Extended ME at LFU analysis set)

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    End point title
    Per-patient microbiological response at LFU (Extended ME at LFU analysis set)
    End point description
    Proportion of patients with a favorable per patient microbiological response at LFU
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    251
    272
    Units: Participants
    number (not applicable)
        Favorable
    184
    173
        Favorable response rate
    73.3
    63.6
        Unfavorable
    67
    99
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    9.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.72
         upper limit
    17.55

    Secondary: Investigator determined clinical response at EOT (IV) (mMITT analysis set)

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    End point title
    Investigator determined clinical response at EOT (IV) (mMITT analysis set)
    End point description
    Proportion of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Clinical cure
    378
    407
        Clinical cure rate
    96.2
    97.6
        Clinical failure
    5
    5
        Indeterminate
    10
    5
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.07
         upper limit
    1.02

    Secondary: Investigator determined clinical response at TOC (mMITT analysis set)

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    End point title
    Investigator determined clinical response at TOC (mMITT analysis set)
    End point description
    Proportion of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Clinical cure
    355
    377
        Clinical cure rate
    90.3
    90.4
        Clinical failure
    11
    24
        Indeterminate
    27
    16
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.23
         upper limit
    4.03

    Secondary: Investigator determined clinical response at LFU (mMITT analysis set)

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    End point title
    Investigator determined clinical response at LFU (mMITT analysis set)
    End point description
    Proportion of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Clinical cure
    335
    350
        Clinical cure rate
    85.2
    83.9
        Clinical failure
    23
    39
        Indeterminate
    35
    28
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.71
         upper limit
    6.3

    Secondary: Investigator determined clinical response at EOT (IV) (ME at EOT (IV) analysis set)

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    End point title
    Investigator determined clinical response at EOT (IV) (ME at EOT (IV) analysis set)
    End point description
    Proportion of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    325
    361
    Units: Participants
    number (not applicable)
        Clinical cure
    318
    358
        Clinical cure rate
    97.8
    99.2
        Clinical failure
    4
    2
        Indeterminate
    3
    1
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    686
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.64
         upper limit
    0.55

    Secondary: Investigator determined clinical response at TOC (ME at TOC analysis set)

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    End point title
    Investigator determined clinical response at TOC (ME at TOC analysis set)
    End point description
    Proportion of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participants
    number (not applicable)
        Clinical cure
    277
    285
        Clinical cure rate
    96.9
    95.6
        Clinical failure
    4
    13
        Indeterminate
    5
    0
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    584
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.03
         upper limit
    4.56

    Secondary: Investigator determined clinical response at LFU (ME at LFU analysis set)

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    End point title
    Investigator determined clinical response at LFU (ME at LFU analysis set)
    End point description
    Proportion of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    245
    262
    Units: Participants
    number (not applicable)
        Clinical cure
    226
    236
        Clinical cure rate
    92.2
    90.1
        Clinical failure
    15
    24
        Indeterminate
    4
    2
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    507
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    2.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    7.24

    Secondary: Investigator determined clinical response at EOT (IV) (Extended ME at EOT (IV) analysis set)

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    End point title
    Investigator determined clinical response at EOT (IV) (Extended ME at EOT (IV) analysis set)
    End point description
    Proportion of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    336
    371
    Units: Participants
    number (not applicable)
        Clinical cure
    327
    368
        Clinical cure rate
    97.3
    99.2
        Clinical failure
    4
    2
        Indeterminate
    5
    1
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    -1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.3
         upper limit
    0.04

    Secondary: Investigator determined clinical response at TOC (Extended ME at TOC analysis set)

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    End point title
    Investigator determined clinical response at TOC (Extended ME at TOC analysis set)
    End point description
    Proportion of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participants
    number (not applicable)
        Clinical cure
    283
    298
        Clinical cure rate
    96.9
    95.8
        Clinical failure
    4
    13
        Indeterminate
    5
    0
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    603
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.07
         upper limit
    4.32

    Secondary: Investigator determined clinical response at LFU (Extended ME at LFU analysis set)

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    End point title
    Investigator determined clinical response at LFU (Extended ME at LFU analysis set)
    End point description
    Proportion of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    251
    272
    Units: Participants
    number (not applicable)
        Clinical cure
    232
    246
        Clinical cure rate
    92.4
    90.4
        Clinical failure
    15
    24
        Indeterminate
    4
    2
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.94
         upper limit
    6.91

    Secondary: Investigator determined clinical response at EOT (IV) (CE at EOT (IV) analysis set)

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    End point title
    Investigator determined clinical response at EOT (IV) (CE at EOT (IV) analysis set)
    End point description
    Proportion of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    350
    391
    Units: Participants
    number (not applicable)
        Clinical cure
    346
    387
        Clinical cure rate
    98.9
    99
        Clinical failure
    4
    4
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    741
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.99
         upper limit
    1.61

    Secondary: Investigator determined clinical response at TOC (CE at TOC analysis set)

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    End point title
    Investigator determined clinical response at TOC (CE at TOC analysis set)
    End point description
    Proportion of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    297
    330
    Units: Participants
    number (not applicable)
        Clinical cure
    289
    309
        Clinical cure rate
    97.3
    93.6
        Clinical failure
    8
    21
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    627
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    3.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.41
         upper limit
    7.16

    Secondary: Investigator determined clinical response at LFU (CE at LFU analysis set)

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    End point title
    Investigator determined clinical response at LFU (CE at LFU analysis set)
    End point description
    Proportion of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient’s clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient’s clinical response.
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    254
    287
    Units: Participants
    number (not applicable)
        Clinical cure
    235
    254
        Clinical cure rate
    92.5
    88.5
        Clinical failure
    19
    33
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    541
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clinical cure rates
    Point estimate
    4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    9.05

    Secondary: Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (mMITT analysis set)

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    End point title
    Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (mMITT analysis set)
    End point description
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        All patients - Clinical cure (n=75, 84)
    67
    75
        All patients - Clinical cure rate
    89.3
    89.3
        Escherichia coli patients - Clin cure (n=36, 37)
    33
    31
        Klebsiella pneumoniae patients-Clin cure(n=18,30)
    17
    28
        Pseudomonas aeruginosa patients- Clin cure(n=7,6)
    5
    6
        Enterobacter cloacae patients-Clin cure(n=7,6)
    5
    5
        Proteus mirabilis patients - Clin cure (n=2, 5)
    2
    5
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clin cure rates in All patients
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.4
         upper limit
    10.1

    Secondary: Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (ME at TOC analysis set)

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    End point title
    Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (ME at TOC analysis set)
    End point description
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participants
    number (not applicable)
        All patients - Clinical cure (n=48, 57)
    47
    55
        All patients - Clinical cure rate
    97.9
    96.5
        Escherichia coli patients-Clin cure (n=23,27)
    22
    25
        Klebsiella pneumoniae patients-Clin cure(n=14,22)
    14
    22
        Pseudomonas aeruginosa patients-Clin cure(n=1, 2)
    1
    2
        Enterobacter cloacae patients-Clin cure(n=5,5)
    5
    5
        Proteus mirabilis patients - Clin cure (n=0, 2)
    0
    2
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    584
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clin cure rates in All patients
    Point estimate
    1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.8
         upper limit
    10.2

    Secondary: Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (Extended ME at TOC analysis set)

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    End point title
    Investigator determined clinical response at TOC for patients infected by ceftazidime-resistant Gram-negative pathogen (Extended ME at TOC analysis set)
    End point description
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participants
    number (not applicable)
        All patients - Clinical cure (n=51, 63)
    50
    61
        All patients - Clinical cure rate
    98
    96.8
        Escherichia coli patients - Clin cure (n=23, 27)
    22
    25
        Klebsiella pneumoniae patients-Clin cure(n=15,23)
    15
    23
        Pseudomonas aeruginosa patients-Clin cure(n=3,6)
    3
    6
        Enterobacter cloacae patients-Clin cure(n=5,5)
    5
    5
        Proteus mirabilis patients - Clin cure (n=0, 2)
    0
    2
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    603
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of clin cure rates in All patients
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.5
         upper limit
    9.2

    Secondary: Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (mMITT analysis set)

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    End point title
    Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (mMITT analysis set)
    End point description
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    75
    84
    Units: Participants
    number (not applicable)
        Favorable
    47
    51
        Favorable response rate
    62.7
    60.7
        Unfavorable
    19
    27
        Indeterminate
    9
    6
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.18
         upper limit
    16.89

    Secondary: Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (ME at TOC analysis set)

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    End point title
    Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (ME at TOC analysis set)
    End point description
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    48
    57
    Units: Participants
    number (not applicable)
        Favorable
    35
    37
        Favorable response rate
    72.9
    64.9
        Unfavorable
    13
    20
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.03
         upper limit
    25.21

    Secondary: Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (Extended ME at TOC analysis set)

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    End point title
    Per-patient microbiological response at TOC in patients infected by ceftazidime-resistant Gram-negative pathogen (Extended ME at TOC analysis set)
    End point description
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set.
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    51
    63
    Units: Participants
    number (not applicable)
        Favorable
    37
    41
        Favorable response rate
    72.5
    65.1
        Unfavorable
    14
    22
    Statistical analysis title
    Confidence interval
    Statistical analysis description
    Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Unstratified Miettinen & Nurminen method
    Parameter type
    Diff of favorable response rates
    Point estimate
    7.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.91
         upper limit
    24.01

    Secondary: Time to first defervescence while on IV study therapy (mMITT analysis set)

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    End point title
    Time to first defervescence while on IV study therapy (mMITT analysis set)
    End point description
    Time to first defervescence while on IV study therapy in patients in the mMITT analysis set who have fever at study entry.
    End point type
    Secondary
    End point timeframe
    Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participants
    number (not applicable)
        Number of patients with fever (>38°C) at baseline
    157
    150
        Number afebrile at the time of the last obs
    155
    143
        Number censored at the time of the last obs
    2
    7
        Median time (days) to defervescence
    2
    3
    Statistical analysis title
    Analysis of time to first defervescence
    Statistical analysis description
    H0: No difference in time to first defervescence between treatment groups
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.038
    Method
    Logrank
    Confidence interval

    Secondary: Time to first defervescence while on IV study therapy (ME at TOC analysis set)

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    End point title
    Time to first defervescence while on IV study therapy (ME at TOC analysis set)
    End point description
    Time to first defervescence while on IV study therapy in patients in the ME at TOC analysis set who have fever at study entry.
    End point type
    Secondary
    End point timeframe
    Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participants
    number (not applicable)
        Number of patients with fever (>38°C) at baseline
    124
    108
        Number afebrile at the time of the last obs
    124
    105
        Number censored at the time of the last obs
    0
    3
        Median time (days) to defervescence
    3
    3
    Statistical analysis title
    Analysis of time to first defervescence
    Statistical analysis description
    H0: No difference in time to first defervescence between treatment groups
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    584
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.129
    Method
    Logrank
    Confidence interval

    Secondary: Time to first defervescence while on IV study therapy (Extended ME at TOC analysis set)

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    End point title
    Time to first defervescence while on IV study therapy (Extended ME at TOC analysis set)
    End point description
    Time to first defervescence while on IV study therapy in patients in the Extended ME at TOC analysis set who have fever at study entry.
    End point type
    Secondary
    End point timeframe
    Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participants
    number (not applicable)
        Number of patients with fever (>38°C) at baseline
    124
    111
        Number afebrile at the time of the last obs
    124
    108
        Number censored at the time of the last obs
    0
    3
        Median time (days) to defervescence
    3
    3
    Statistical analysis title
    Analysis of time to first defervescence
    Statistical analysis description
    H0: No difference in time to first defervescence between treatment groups
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    603
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.08
    Method
    Logrank
    Confidence interval

    Secondary: Time to first defervescence while on IV study therapy (CE at TOC analysis set)

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    End point title
    Time to first defervescence while on IV study therapy (CE at TOC analysis set)
    End point description
    Time to first defervescence while on IV study therapy in patients in the CE at TOC analysis set who have fever at study entry.
    End point type
    Secondary
    End point timeframe
    Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    297
    330
    Units: Participants
    number (not applicable)
        Number of patients with fever (>38°C) at baseline
    123
    118
        Number afebrile at the time of the last obs
    122
    113
        Number censored at the time of the last obs
    1
    5
        Median time (days) to defervescence
    3
    3
    Statistical analysis title
    Analysis of time to first defervescence
    Statistical analysis description
    H0: No difference in time to first defervescence between treatment groups
    Comparison groups
    CAZ-AVI v Doripenem
    Number of subjects included in analysis
    627
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.155
    Method
    Logrank
    Confidence interval

    Secondary: Per-pathogen microbiological response at EOT (IV) for baseline pathogen (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for baseline pathogen (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set
    End point type
    Secondary
    End point timeframe
    At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=292, 306)
    280
    293
        Klebsiella pneumoniae - Favorable (n=44, 56)
    41
    51
        Proteus mirabilis - Favorable (n=17, 13)
    16
    11
        Enterobacter cloacae - Favorable (n= 11,13)
    9
    13
        Pseudomonas aeruginosa - Favorable (n=18, 20)
    17
    18
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for baseline pathogen (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for baseline pathogen (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=292, 306)
    229
    220
        Klebsiella pneumoniae - Favorable (n=44, 56)
    33
    35
        Proteus mirabilis - Favorable (n=17, 13)
    16
    9
        Enterobacter cloacae - Favorable (n= 11,13)
    6
    9
        Pseudomonas aeruginosa - Favorable (n=18, 20)
    12
    15
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for baseline pathogen (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for baseline pathogen (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=292, 306)
    198
    189
        Klebsiella pneumoniae - Favorable (n=44, 56)
    32
    30
        Proteus mirabilis - Favorable (n=17, 13)
    16
    6
        Enterobacter cloacae - Favorable (n= 11,13)
    6
    9
        Pseudomonas aeruginosa - Favorable (n=18, 20)
    9
    13
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at EOT (IV) for baseline pathogen (Extended ME at EOT (IV) analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for baseline pathogen (Extended ME at EOT (IV) analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set
    End point type
    Secondary
    End point timeframe
    At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    336
    371
    Units: Participant
        Escherichia coli - Favorable (n=250, 274)
    250
    274
        Klebsiella pneumoniae - Favorable (n=34, 49)
    34
    48
        Proteus mirabilis - Favorable (n=13, 11)
    13
    11
        Enterobacter cloacae - Favorable (n= 9, 12)
    9
    12
        Pseudomonas aeruginosa - Favorable (n=18, 18)
    17
    17
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for baseline pathogen (Extended ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for baseline pathogen (Extended ME at TOC analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participant
        Escherichia coli - Favorable (n=214, 226)
    180
    176
        Klebsiella pneumoniae - Favorable (n=32, 42)
    26
    29
        Proteus mirabilis - Favorable (n=14, 7)
    14
    4
        Enterobacter cloacae - Favorable (n= 7, 11)
    5
    8
        Pseudomonas aeruginosa - Favorable (n=13, 18)
    8
    13
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for baseline pathogen (Extended ME at LFU analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for baseline pathogen (Extended ME at LFU analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    251
    272
    Units: Participant
        Escherichia coli - Favorable (n=179, 198)
    129
    131
        Klebsiella pneumoniae - Favorable (n=31, 36)
    24
    19
        Proteus mirabilis - Favorable (n=11,5)
    11
    1
        Enterobacter cloacae - Favorable (n= 7, 11)
    5
    8
        Pseudomonas aeruginosa - Favorable (n=12, 16)
    7
    9
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at EOT (IV) for baseline pathogen (ME at EOT (IV) analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for baseline pathogen (ME at EOT (IV) analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    325
    361
    Units: Participant
        Escherichia coli - Favorable (n=249, 270)
    249
    270
        Klebsiella pneumoniae - Favorable (n=33, 48)
    33
    47
        Proteus mirabilis - Favorable (n=13,11)
    13
    11
        Enterobacter cloacae - Favorable (n= 9, 12)
    9
    12
        Pseudomonas aeruginosa - Favorable (n=10, 15)
    9
    14
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for baseline pathogen (ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for baseline pathogen (ME at TOC analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participant
        Escherichia coli - Favorable (n=214, 221)
    180
    171
        Klebsiella pneumoniae - Favorable (n=31, 41)
    25
    28
        Proteus mirabilis - Favorable (n=14, 7)
    14
    4
        Enterobacter cloacae - Favorable (n= 7, 11)
    5
    8
        Pseudomonas aeruginosa - Favorable (n=9, 13)
    7
    9
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for baseline pathogen (ME at LFU analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for baseline pathogen (ME at LFU analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    245
    262
    Units: Participant
        Escherichia coli - Favorable (n=179, 194)
    129
    127
        Klebsiella pneumoniae - Favorable (n=30, 35)
    23
    18
        Proteus mirabilis - Favorable (n=11,5)
    11
    1
        Enterobacter cloacae - Favorable (n= 7, 11)
    5
    8
        Pseudomonas aeruginosa - Favorable (n=8, 13)
    6
    8
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at EOT (IV) for blood only (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for blood only (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=32, 28)
    31
    28
        Klebsiella pneumoniae - Favorable (n=4, 2)
    2
    2
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=1, 2)
    1
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for blood only (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for blood only (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=32, 28)
    31
    28
        Klebsiella pneumoniae - Favorable (n=4, 2)
    3
    2
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=1, 2)
    1
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for blood only (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for blood only (mMITT analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        Escherichia coli - Favorable (n=32, 28)
    29
    27
        Klebsiella pneumoniae - Favorable (n=4, 2)
    3
    2
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=1, 2)
    1
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at EOT (IV) for blood only (Extended ME at EOT (IV) analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for blood only (Extended ME at EOT (IV) analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    336
    371
    Units: Participant
        Escherichia coli - Favorable (n=26, 24)
    26
    24
        Klebsiella pneumoniae - Favorable (n=2, 1)
    1
    1
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=1, 2)
    1
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for blood only (Extended ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for blood only (Extended ME at TOC analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participant
        Escherichia coli - Favorable (n=22, 20)
    22
    20
        Klebsiella pneumoniae - Favorable (n=2, 2)
    2
    2
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=0, 1)
    0
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for blood only (Extended ME at LFU analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for blood only (Extended ME at LFU analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    251
    272
    Units: Participant
        Escherichia coli - Favorable (n=19, 18)
    19
    17
        Klebsiella pneumoniae - Favorable (n=2, 1)
    2
    1
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=0, 1)
    0
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at EOT (IV) for blood only (ME at EOT (IV) analysis set) 

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    End point title
    Per-pathogen microbiological response at EOT (IV) for blood only (ME at EOT (IV) analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    325
    361
    Units: Participant
        Escherichia coli - Favorable (n=26, 24)
    26
    24
        Klebsiella pneumoniae - Favorable (n=2, 1)
    1
    1
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=1, 2)
    1
    2
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC for blood only (ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC for blood only (ME at TOC analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participant
        Escherichia coli - Favorable (n=22, 20)
    22
    20
        Klebsiella pneumoniae - Favorable (n=2, 2)
    2
    2
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=0, 1)
    0
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at LFU for blood only (ME at LFU analysis set) 

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    End point title
    Per-pathogen microbiological response at LFU for blood only (ME at LFU analysis set) 
    End point description
    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set for blood only
    End point type
    Secondary
    End point timeframe
    At LFU visit. LFU visit is 45 to 52 days from Randomization.
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    245
    262
    Units: Participant
        Escherichia coli - Favorable (n=19, 18)
    19
    17
        Klebsiella pneumoniae - Favorable (n=2, 1)
    2
    1
        Proteus mirabilis - Favorable (n=1, 0)
    1
    0
        Pseudomonas aeruginosa - Favorable (n=0, 1)
    0
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (mMITT analysis set) 
    End point description
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the mMITT analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=5, 6)
    3
    5
        E. coli (MIC: 0.015) - Favorable (n=8, 7)
    8
    6
        E. coli (MIC: 0.03) - Favorable (n=28, 35)
    24
    23
        E. coli (MIC: 0.06) - Favorable (n=123, 139)
    103
    111
        E. coli (MIC: 0.12) - Favorable (n=90, 81)
    67
    54
        E. coli (MIC: 0.25) - Favorable (n=28, 25)
    18
    13
        E. coli (MIC: 0.5) - Favorable (n=5, 6)
    4
    2
        E. coli (MIC: 1) - Favorable (n=3, 0)
    1
    0
        E. coli (MIC: 2) - Favorable (n=1, 0)
    1
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 32) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >32) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) -Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
    1
    2
        Kleb. pneumoniae (MIC: 0.06) - Favorable (n=9, 8)
    7
    8
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=11, 10)
    9
    7
        Kleb. pneumoniae (MIC: 0.25) - Favorable(n=4, 10)
    1
    3
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=8, 16)
    6
    11
        Kleb. pneumoniae (MIC: 1) - Favorable (n=8, 5)
    6
    3
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 4)
    2
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 1)
    0
    1
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=1,1)
    1
    0
        Proteus mirabilis (MIC: 0.03)- Favorable(n=10, 5)
    10
    3
        Proteus mirabilis (MIC: 0.06)- Favorable (n=6,6)
    5
    5
        Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 0.5)- Favorable (n=0,1)
    0
    1
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
    0
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 3,2)
    2
    2
        Entero. cloacae (MIC: 0.25)- Favorable (n= 1,4)
    0
    1
        Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
    0
    1
        Entero. cloacae (MIC: 1)- Favorable (n= 2,5)
    1
    4
        Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
    1
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.5) - Favorable (n=0,2)
    0
    2
        P.aeruginosa (MIC: 1) - Favorable (n=1,4)
    1
    2
        P.aeruginosa (MIC: 2) - Favorable (n=5,5)
    5
    5
        P.aeruginosa (MIC: 4) - Favorable (n=7,6)
    3
    4
        P.aeruginosa (MIC: 8) - Favorable (n=2,2)
    1
    1
        P.aeruginosa (MIC: 16) - Favorable (n=1,1)
    0
    1
        P.aeruginosa (MIC: 32) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: >32) - Favorable (n=2,0)
    2
    0
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (Extended ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (Extended ME at TOC analysis set) 
    End point description
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the Extended ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=4,4)
    2
    4
        E. coli (MIC: 0.015) - Favorable (n=5, 6)
    5
    5
        E. coli (MIC: 0.03) - Favorable (n=18, 21)
    17
    17
        E. coli (MIC: 0.06) - Favorable (n=95, 111)
    83
    94
        E. coli (MIC: 0.12) - Favorable (n=68, 54)
    56
    40
        E. coli (MIC: 0.25) - Favorable (n=19, 18)
    13
    8
        E. coli (MIC: 0.5) - Favorable (n=2, 5)
    2
    2
        E. coli (MIC: 1) - Favorable (n=2, 0)
    1
    0
        E. coli (MIC: 2) - Favorable (n=1, 0)
    1
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 32) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >32) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) - Favorable(n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
    1
    2
        Kleb. pneumoniae (MIC: 0.06) - Favorable (n=5, 7)
    4
    7
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=8, 9)
    7
    6
        Kleb. pneumoniae (MIC: 0.25) - Favorable (n=3, 7)
    1
    2
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=6, 11)
    4
    8
        Kleb. pneumoniae (MIC: 1) - Favorable (n=6, 4)
    6
    3
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 1)
    2
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 1)
    0
    1
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=1,0)
    1
    0
        Proteus mirabilis (MIC: 0.03)- Favorable (n=9, 2)
    9
    0
        Proteus mirabilis (MIC: 0.06)- Favorable (n=4,5)
    4
    4
        Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 0.5)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
    0
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 1,2)
    1
    2
        Entero. cloacae (MIC: 0.25)- Favorable (n= 0,3)
    0
    0
        Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
    0
    1
        Entero. cloacae (MIC: 1)- Favorable (n= 1,4)
    1
    4
        Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
    1
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.5) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 1) - Favorable (n=1,4)
    1
    2
        P.aeruginosa (MIC: 2) - Favorable (n=4,5)
    4
    5
        P.aeruginosa (MIC: 4) - Favorable (n=5,6)
    1
    4
        P.aeruginosa (MIC: 8) - Favorable (n=2,2)
    1
    1
        P.aeruginosa (MIC: 16) - Favorable (n=0,1)
    0
    1
        P.aeruginosa (MIC: 32) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: >32) - Favorable (n=1,0)
    1
    0
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by CAZ AVI MIC for baseline pathogen (ME at TOC analysis set) 
    End point description
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=4,4)
    2
    4
        E. coli (MIC: 0.015) - Favorable (n=5, 6)
    5
    5
        E. coli (MIC: 0.03) - Favorable (n=18, 21)
    17
    17
        E. coli (MIC: 0.06) - Favorable (n=95, 111)
    83
    94
        E. coli (MIC: 0.12) - Favorable (n=68, 54)
    56
    40
        E. coli (MIC: 0.25) - Favorable (n=19, 18)
    13
    8
        E. coli (MIC: 0.5) - Favorable (n=2, 5)
    2
    2
        E. coli (MIC: 1) - Favorable (n=2, 0)
    1
    0
        E. coli (MIC: 2) - Favorable (n=1, 0)
    1
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 32) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >32) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) -Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
    1
    2
        Kleb. pneumoniae (MIC: 0.06) - Favorable (n=5, 7)
    4
    7
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=8, 9)
    7
    6
        Kleb. pneumoniae (MIC: 0.25) - Favorable (n=3, 7)
    1
    2
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=6, 11)
    4
    8
        Kleb. pneumoniae (MIC: 1) - Favorable (n=5, 4)
    5
    3
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 1)
    2
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=1,0)
    1
    0
        Proteus mirabilis (MIC: 0.03)- Favorable (n=9, 2)
    9
    0
        Proteus mirabilis (MIC: 0.06)- Favorable (n=4,5)
    4
    4
        Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 0.5)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
    0
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 1,2)
    1
    2
        Entero. cloacae (MIC: 0.25)- Favorable (n= 0,3)
    0
    0
        Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
    0
    1
        Entero. cloacae (MIC: 1)- Favorable (n= 1,4)
    1
    4
        Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
    1
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
    1
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.5) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 1) - Favorable (n=1,4)
    1
    2
        P.aeruginosa (MIC: 2) - Favorable (n=4,4)
    4
    4
        P.aeruginosa (MIC: 4) - Favorable (n=3,4)
    1
    3
        P.aeruginosa (MIC: 8) - Favorable (n=1,1)
    1
    0
        P.aeruginosa (MIC: 16) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 32) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: >32) - Favorable (n=0,0)
    0
    0
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (mMITT analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (mMITT analysis set) 
    End point description
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the mMITT analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    393
    417
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=1, 3)
    1
    3
        E. coli (MIC: 0.015) - Favorable (n=160, 160)
    127
    119
        E. coli (MIC: 0.03) - Favorable (n=112, 123)
    89
    86
        E. coli (MIC: 0.06) - Favorable (n=14, 10)
    10
    4
        E. coli (MIC: 0.12) - Favorable (n=3, 3)
    1
    2
        E. coli (MIC: 0.25) - Favorable (n=1, 0)
    1
    0
        E. coli (MIC: 0.5) - Favorable (n=0,0)
    0
    0
        E. coli (MIC: 1) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 2) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >16) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) - Favorable(n=1, 3)
    1
    2
        Kleb. pneumoniae (MIC: 0.03)-Favorable (n=22, 27)
    16
    21
        Kleb. pneumoniae (MIC: 0.06)- Favorable(n=11, 16)
    10
    7
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=4,4)
    2
    2
        Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2,3)
    1
    2
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=2, 1)
    1
    0
        Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 1)
    0
    1
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 1)
    0
    0
        Kleb. pneumoniae (MIC: >16) - Favorable (n=1, 0)
    1
    0
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.03)- Favorable (n=1, 0)
    1
    0
        Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
    2
    1
        Proteus mirabilis (MIC: 0.12)- Favorable (n=6,5)
    5
    4
        Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 4)
    6
    2
        Proteus mirabilis (MIC: 0.5)- Favorable (n=2,2)
    2
    2
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 3,1)
    2
    1
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,5)
    1
    2
        Entero. cloacae (MIC: 0.06)- Favorable (n= 3, 1)
    1
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 0, 4)
    0
    4
        Entero. cloacae (MIC: 0.25)- Favorable (n= 0,1)
    0
    0
        Entero. cloacae (MIC: 0.5)- Favorable (n= 4,0)
    2
    0
        Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
    0
    1
        Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
    2
    3
        P.aeruginosa (MIC: 0.12) - Favorable (n=2,2)
    1
    2
        P.aeruginosa (MIC: 0.25) - Favorable (n=2,5)
    2
    2
        P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
    2
    1
        P.aeruginosa (MIC: 1) - Favorable (n=1,4)
    0
    3
        P.aeruginosa (MIC: 2) - Favorable (n=1,0)
    1
    0
        P.aeruginosa (MIC: 4) - Favorable (n=2,2)
    1
    1
        P.aeruginosa (MIC: 8) - Favorable (n=2,1)
    1
    1
        P.aeruginosa (MIC: 16) - Favorable (n=2,1)
    0
    1
        P.aeruginosa (MIC: >16) - Favorable (n=2,1)
    2
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (Extended ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (Extended ME at TOC analysis set) 
    End point description
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the Extended ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    292
    311
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=1,1)
    1
    1
        E. coli (MIC: 0.015) - Favorable (n=122, 119)
    106
    95
        E. coli (MIC: 0.03) - Favorable (n=79, 89)
    64
    70
        E. coli (MIC: 0.06) - Favorable (n=10, 8)
    7
    3
        E. coli (MIC: 0.12) - Favorable (n=1, 2)
    1
    1
        E. coli (MIC: 0.25) - Favorable (n=1, 0)
    1
    0
        E. coli (MIC: 0.5) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 1) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 2) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >16) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) - Favorable(n=1, 2)
    1
    1
        Kleb. pneumoniae (MIC:0.03) - Favorable(n=15, 23)
    12
    18
        Kleb. pneumoniae (MIC: 0.06) - Favorable(n=8, 12)
    7
    6
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=3, 2)
    2
    2
        Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2, 2)
    1
    1
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 0,0)
    0
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 1)
    0
    1
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: >16) - Favorable (n=1, 0)
    1
    0
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.03)- Favorable (n=1,0)
    1
    0
        Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
    2
    1
        Proteus mirabilis (MIC: 0.12)- Favorable (n=4,2)
    4
    2
        Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 3)
    6
    1
        Proteus mirabilis (MIC: 0.5)- Favorable (n=1,0)
    1
    0
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 1,1)
    1
    1
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,4)
    1
    1
        Entero. cloacae (MIC: 0.06)- Favorable (n= 2, 1)
    1
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 0,4)
    0
    4
        Entero. cloacae (MIC: 0.25)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.5)- Favorable (n= 3,0)
    2
    0
        Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
    0
    1
        Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
    2
    3
        P.aeruginosa (MIC: 0.12) - Favorable (n=1,2)
    0
    2
        P.aeruginosa (MIC: 0.25) - Favorable (n=2,4)
    2
    1
        P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
    2
    1
        P.aeruginosa (MIC: 1) - Favorable (n=1,3)
    0
    2
        P.aeruginosa (MIC: 2) - Favorable (n=1,0)
    1
    0
        P.aeruginosa (MIC: 4) - Favorable (n=0,2)
    0
    1
        P.aeruginosa (MIC: 8) - Favorable (n=1,1)
    0
    1
        P.aeruginosa (MIC: 16) - Favorable (n=2,1)
    0
    1
        P.aeruginosa (MIC: >16) - Favorable (n=1,1)
    1
    1
    No statistical analyses for this end point

    Secondary: Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (ME at TOC analysis set) 

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    End point title
    Per-pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen (ME at TOC analysis set) 
    End point description
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the ME at TOC analysis set
    End point type
    Secondary
    End point timeframe
    At TOC visit. TOC visit is 21 to 25 days from Randomization
    End point values
    CAZ-AVI Doripenem
    Number of subjects analysed
    286
    298
    Units: Participant
        E. coli (MIC: <=0.008) - Favorable (n=1,1)
    1
    1
        E. coli (MIC: 0.015) - Favorable (n=122, 119)
    106
    95
        E. coli (MIC: 0.03) - Favorable (n=79, 89)
    64
    70
        E. coli (MIC: 0.06) - Favorable (n=10, 8)
    7
    3
        E. coli (MIC: 0.12) - Favorable (n=1,2)
    1
    1
        E. coli (MIC: 0.25) - Favorable (n=1,0)
    1
    0
        E. coli (MIC: 0.5) - Favorable (n=0,0)
    0
    0
        E. coli (MIC: 1) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 2) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 4) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 8) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: 16) - Favorable (n=0, 0)
    0
    0
        E. coli (MIC: >16) - Favorable (n=0, 0)
    0
    0
        Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 0.015) - Favorable(n=1, 2)
    1
    1
        Kleb. pneumoniae (MIC:0.03) - Favorable(n=15, 23)
    12
    18
        Kleb. pneumoniae (MIC: 0.06) - Favorable(n=8, 12)
    7
    6
        Kleb.pneumoniae (MIC: 0.12) -Favorable(n=3,2)
    2
    2
        Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2, 2)
    1
    1
        Kleb. pneumoniae (MIC: 0.5) - Favorable (n=1,0)
    1
    0
        Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
    1
    0
        Kleb. pneumoniae (MIC: 2) - Favorable (n= 0,0)
    0
    0
        Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
    0
    0
        Kleb. pneumoniae (MIC: >16) - Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC:<=0.008)- Favorable(n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
    0
    0
        Proteus mirabilis (MIC: 0.03)- Favorable (n=1, 0)
    1
    0
        Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
    2
    1
        Proteus mirabilis (MIC: 0.12)- Favorable (n=4,2)
    4
    2
        Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 3)
    6
    1
        Proteus mirabilis (MIC: 0.5)- Favorable (n=1,0)
    1
    0
        Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
    0
    0
        Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
    0
    0
        Entero. cloacae (MIC: <=0.008)- Favorable(n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.015)- Favorable (n= 1,1)
    1
    1
        Entero. cloacae (MIC: 0.03)- Favorable (n= 1,4)
    1
    1
        Entero. cloacae (MIC: 0.06)- Favorable (n= 2, 1)
    1
    1
        Entero. cloacae (MIC: 0.12)- Favorable (n= 0,4)
    0
    4
        Entero. cloacae (MIC: 0.25)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 0.5)- Favorable (n= 3,0)
    2
    0
        Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
    0
    1
        Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
    0
    0
        Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
    0
    0
        P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
    2
    3
        P.aeruginosa (MIC: 0.12) - Favorable (n=1,2)
    0
    2
        P.aeruginosa (MIC: 0.25) - Favorable (n=2,4)
    2
    1
        P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
    2
    1
        P.aeruginosa (MIC: 1) - Favorable (n=1,3)
    0
    2
        P.aeruginosa (MIC: 2) - Favorable (n=1,0)
    1
    0
        P.aeruginosa (MIC: 4) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 8) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: 16) - Favorable (n=0,0)
    0
    0
        P.aeruginosa (MIC: >16) - Favorable (n=0,0)
    0
    0
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for ceftazidime within 15 minutes before/after dose (PK analysis set) [4]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    within 15 minutes before/after dose
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    480
    Units: Participant
        geometric mean (full range (min-max))
    65481.2 (1260 to 3190000)
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for ceftazidime between 30 to 90 minutes after dose(PK analysis set) [5]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    Between 30 to 90 minutes after dose
    Notes
    [5] - 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: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    483
    Units: Participant
        geometric mean (full range (min-max))
    47575.1 (749 to 414000)
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for avibactam within 15 minutes before/after dose (PK analysis set) [6]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    within 15 minutes before/after dose
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    489
    Units: Participant
        geometric mean (full range (min-max))
    9307.3 (125 to 1780000)
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for ceftazidime between 300 to 360 minutes after dose(PK analysis set) [7]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    Between 300 to 360 minutes after dose
    Notes
    [7] - 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: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    481
    Units: Participant
        geometric mean (full range (min-max))
    16959.6 (156 to 1640000)
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for avibactam between 30 to 90 minutes after dose(PK analysis set) [8]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    Between 30 to 90 minutes after dose
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    490
    Units: Participant
        geometric mean (full range (min-max))
    6587.2 (113 to 105000)
    No statistical analyses for this end point

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

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    End point title
    Plasma concentrations for avibactam between 300 to 360 minutes after dose(PK analysis set) [9]
    End point description
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
    End point type
    Secondary
    End point timeframe
    Between 300 to 360 minutes after dose
    Notes
    [9] - 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: The marketed treatment ‘Doripenem’ has been selected as the comparator in this protocol. However, the PK profile has already been established for the marketed treatment ‘Doripenem’. Therefore, the PK analysis is only performed on the investigational product ‘CAZ-AVI’ in this protocol.
    End point values
    CAZ-AVI
    Number of subjects analysed
    488
    Units: Participant
        geometric mean (full range (min-max))
    1883.2 (26 to 336000)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Includes the AEs with an onset date and time on or after the date and time of first dose and up to and including the late follow-up (LFU) visit
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Doripenem
    Reporting group description
    Doripenem treatment group

    Reporting group title
    CAZ-AVI
    Reporting group description
    Ceftazidime-avibactam treatment group

    Serious adverse events
    Doripenem CAZ-AVI
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 509 (2.36%)
    21 / 511 (4.11%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Procedural haemorrhage
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 511 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery aneurysm
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hyperventilation
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hypoglycaemic seizure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 509 (0.00%)
    3 / 511 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Spinal pain
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic hepatitis C
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 511 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 511 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Doripenem CAZ-AVI
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 509 (11.20%)
    67 / 511 (13.11%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    40 / 509 (7.86%)
    38 / 511 (7.44%)
         occurrences all number
    41
    41
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    10 / 509 (1.96%)
    15 / 511 (2.94%)
         occurrences all number
    10
    16
    Diarrhoea
         subjects affected / exposed
    6 / 509 (1.18%)
    13 / 511 (2.54%)
         occurrences all number
    6
    14
    Constipation
         subjects affected / exposed
    7 / 509 (1.38%)
    11 / 511 (2.15%)
         occurrences all number
    8
    11

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Aug 2013
    Combined the 2 protocols (D4280C00002 and D4280C00004) into a single study database
    09 Aug 2013
    All data analyses based on data from the combined studies (D4280C00002 and D4280C00004)

    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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