Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39235   clinical trials with a EudraCT protocol, of which   6428   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A single blind, randomised, multi-centre, active controlled, trial to evaluate safety, tolerability, pharmacokinetics and efficacy of ceftazidime and avibactam when given in combination with metronidazole, compared with meropenem, in children from 3 months to less than 18 years of age with complicated intra-abdominal infections (cIAIs).

    Summary
    EudraCT number
    2014-003242-28
    Trial protocol
    HU   ES   CZ   GR   RO  
    Global end of trial date
    01 Jun 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Dec 2017
    First version publication date
    13 Dec 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    C3591004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02475733
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001313-PIP01-12
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Aug 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jun 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of ceftazidime and avibactam (CAZ-AVI) plus metronidazole is given at the selected dose regimen versus meropenem in paediatric subjects aged greater than or equal to (>=)3 months to less than (<)18 years with cIAI
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Aug 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Russian Federation: 3
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    Taiwan: 10
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    United States: 12
    Country: Number of subjects enrolled
    Czech Republic: 12
    Country: Number of subjects enrolled
    Greece: 5
    Worldwide total number of subjects
    83
    EEA total number of subjects
    51
    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)
    1
    Children (2-11 years)
    52
    Adolescents (12-17 years)
    30
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Total 83 subjects were enrolled in multiple sites in 10 countries. Study started from 01-Aug-2015 and completed on 01-Jun-2017.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Assessor [1]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Arm description
    Subjects with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received 10 milligram per kilogram (mg/kg) intravenous(IV) infusion of metronidazole over 20 to 30 minutes along with 2 hour IV infusion of CAZ/AVI in following manner: 1)Age 6 to less than(<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3)Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. Both infusions were administered to subjects every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. Dose of CAZ-AVI was reduced to 50% if CrCl of subject decreased to <=50mL/min, and subject was removed from study therapy, if CrCl decreased below 30mL/min. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received 10 milligram per kilogram (mg/kg) intravenous(IV) infusion of metronidazole over 20 to 30 minutes along with 2 hour IV infusion of CAZ/AVI in following manner: 1)Age 6 to less than(<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3)Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. Both infusions were administered to subjects every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days.

    Arm title
    Meropenem
    Arm description
    Subjects received 15 to 30 minutes IV infusion of meropenem 20 mg/kg every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.
    Arm type
    Active comparator

    Investigational medicinal product name
    Meropenem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 15 to 30 minutes IV infusion of meropenem 20 mg/kg every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: The assessor was kept blinded in this study to remove any bias during clinical assessments related to safety and efficacy
    Number of subjects in period 1
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Started
    61
    22
    Completed
    59
    22
    Not completed
    2
    0
         Physician decision
    1
    -
         Consent withdrawn by subject
    1
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Reporting group description
    Subjects with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received 10 milligram per kilogram (mg/kg) intravenous(IV) infusion of metronidazole over 20 to 30 minutes along with 2 hour IV infusion of CAZ/AVI in following manner: 1)Age 6 to less than(<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3)Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. Both infusions were administered to subjects every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. Dose of CAZ-AVI was reduced to 50% if CrCl of subject decreased to <=50mL/min, and subject was removed from study therapy, if CrCl decreased below 30mL/min. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at investigator's discretion.

    Reporting group title
    Meropenem
    Reporting group description
    Subjects received 15 to 30 minutes IV infusion of meropenem 20 mg/kg every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.

    Reporting group values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem Total
    Number of subjects
    61 22 83
    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 1 1
        Children (2-11 years)
    39 13 52
        Adolescents (12-17 years)
    22 8 30
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    10.4 ± 3.64 9.7 ± 3.97 -
    Gender, Male/Female
    Units: Subjects
        Female
    17 13 30
        Male
    44 9 53
    Race/Ethnicity, Customized
    Units: Subjects
        White
    53 16 69
        Asian
    7 4 11
        American Indian or Alaska Native
    1 0 1
        Other
    0 2 2

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Reporting group description
    Subjects with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received 10 milligram per kilogram (mg/kg) intravenous(IV) infusion of metronidazole over 20 to 30 minutes along with 2 hour IV infusion of CAZ/AVI in following manner: 1)Age 6 to less than(<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3)Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. Both infusions were administered to subjects every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. Dose of CAZ-AVI was reduced to 50% if CrCl of subject decreased to <=50mL/min, and subject was removed from study therapy, if CrCl decreased below 30mL/min. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at investigator's discretion.

    Reporting group title
    Meropenem
    Reporting group description
    Subjects received 15 to 30 minutes IV infusion of meropenem 20 mg/kg every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.

    Primary: Percentage of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Close Top of page
    End point title
    Percentage of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [1]
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to late follow-up (LFU) visit (Within 20 to 35 days after last dose of any study drug [IV or oral]) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE. Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    From signature of informed consent until the LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        AEs
    52.5
    59.1
        SAEs
    8.2
    4.5
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Cephalosporin Class Effects and Additional AEs of Special Interest (AEoSI)

    Close Top of page
    End point title
    Percentage of Subjects With Cephalosporin Class Effects and Additional AEs of Special Interest (AEoSI) [2]
    End point description
    Percentage of subjects with Cephalosporin class effects (defined as AeoSI within the safety topics (ST) of hypersensitivity/anaphylaxis, diarrhea, renal disorder and liver disorder) and additional AEs (which included AEs with preferred terms[PT] in the MedDRA 20.0 system organ class [SOC] of nervous system disorders and other AEs of clinical importance [such as seizures] relevant to the cephalosporin class) were reported in this outcome measure. LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral).
    End point type
    Primary
    End point timeframe
    From signature of informed consent until the LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        AEoSI in the ST of Diarrhea
    1.6
    0
        AEoSI in the ST of Hypersensitivity/Anaphylaxis
    4.9
    13.6
        AEoSI in the ST of Liver Disorder
    0
    0
        AEoSI in the ST of Renal Disorder
    0
    0
        AEs with PTs in the Nervous System Disorder SOC
    1.6
    4.5
        AE of seizure
    0
    0
    No statistical analyses for this end point

    Primary: Change From Baseline in Pulse Rate at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Change From Baseline in Pulse Rate at End of Intravenous Therapy (EOIV) Visit [3]
    End point description
    EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    Baseline, EOIV visit (Day 4 up to 16)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: beats per minute
    arithmetic mean (standard deviation)
        Baseline (n= 61, 22)
    102.1 ± 17.07
    103.0 ± 23.31
        Change at EOIV (n= 60, 22)
    -15.2 ± 20.45
    -15.4 ± 21.74
    No statistical analyses for this end point

    Primary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End of Intravenous Therapy (EOIV) Visit [4]
    End point description
    EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    Baseline, EOIV visit (Day 4 up to 16)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP: Baseline (n= 60, 22)
    109.7 ± 13.90
    111.6 ± 13.06
        SBP: Change at EOIV (n= 59, 22)
    -4.0 ± 12.32
    -6.0 ± 13.66
        DBP: Baseline (n= 60, 22)
    63.5 ± 10.36
    63.1 ± 13.51
        DBP: Change at EOIV (n= 59, 22)
    1.3 ± 11.99
    -2.8 ± 14.14
    No statistical analyses for this end point

    Primary: Change From Baseline in Respiratory Rate at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Change From Baseline in Respiratory Rate at End of Intravenous Therapy (EOIV) Visit [5]
    End point description
    EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    Baseline, EOIV visit (Day 4 up to 16)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: breaths per minute
    arithmetic mean (standard deviation)
        Baseline (n= 58, 21)
    22.4 ± 5.02
    22.9 ± 5.79
        Change at EOIV (n= 56, 21)
    -1.3 ± 4.57
    -1.3 ± 4.44
    No statistical analyses for this end point

    Primary: Change From Baseline in Body Weight at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Change From Baseline in Body Weight at End of Intravenous Therapy (EOIV) Visit [6]
    End point description
    EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    Baseline, EOIV visit (Day 4 up to 16)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: kilograms
    arithmetic mean (standard deviation)
        Baseline (n= 61, 22)
    40.58 ± 16.286
    38.35 ± 16.685
        Change at EOIV (n= 56, 20)
    -0.38 ± 1.442
    -1.06 ± 1.490
    No statistical analyses for this end point

    Primary: Change From Baseline in Body Temperature at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Change From Baseline in Body Temperature at End of Intravenous Therapy (EOIV) Visit [7]
    End point description
    EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    Baseline, EOIV visit (Day 4 up to 16)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: degree Celsius
    arithmetic mean (standard deviation)
        Baseline (n= 60, 22)
    37.35 ± 1.035
    37.16 ± 0.914
        Change at EOIV (n= 59, 22)
    -0.78 ± 0.987
    -0.60 ± 0.780
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Abnormal Physical Examination Findings at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Percentage of Subjects With Abnormal Physical Examination Findings at End of Intravenous Therapy (EOIV) Visit [8]
    End point description
    Physical examination included an assessment of the following: general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, respiratory system, cardiovascular system, abdomen, musculoskeletal system (including spine and extremities), and neurological system. Subjects with new or aggravated abnormal physical examination findings with regard to baseline findings were reported. Abnormality in physical examinations were based on blinded observer’s discretion. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    EOIV visit (Day 4 up to 16)
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: subjects of subjects
    number (not applicable)
        Abdomen
    6.6
    18.2
        Cardiovascular System
    0
    0
        General Appearance
    1.6
    0
        Head and Neck
    0
    0
        Lymph Nodes
    0
    0
        Musculoskeletal System
    0
    0
        Neurological System
    0
    0
        Respiratory System
    3.3
    0
        Skin
    1.6
    0
        Thyroid
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Abnormalities in Laboratory Parameters According to Potentially Clinically Significant Criteria

    Close Top of page
    End point title
    Percentage of Subjects With Abnormalities in Laboratory Parameters According to Potentially Clinically Significant Criteria [9]
    End point description
    Criteria for potentially clinically significant laboratory abnormalities: Chemistry (calcium: <0.7*lower limit of normal range [LLN] and >30 percent decrease from baseline [DFB]; alanine aminotransferase [ALT]: >3*upper limit of normal range [ULN] and >300 percent IFB; alanine aminotransferase [AST]: >3*ULN and >300 percent IFB) and hematology (platelets: >2*ULN and >100 percent IFB). LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral). Safety analysis set included all randomized subjects who received any amount of IV study medication. Here, ‘n’ signifies those subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Primary
    End point timeframe
    From signature of informed consent until the LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        Chemistry: Calcium (n= 53, 21)
    1.9
    0
        Chemistry: ALT (n= 59, 22)
    1.7
    0
        Chemistry: AST (n= 55, 21)
    1.8
    0
        Hematology: Platelets (n= 60, 22)
    3.3
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Electrocardiogram (ECG) Parameter QTcF: > 450, >480 and >500 Millisecond (ms)

    Close Top of page
    End point title
    Percentage of Subjects With Electrocardiogram (ECG) Parameter QTcF: > 450, >480 and >500 Millisecond (ms) [10]
    End point description
    ECG parameters included maximum QT intervals using Fridericia’s correction (QTcF). Maximum QTcF >450 millisecond (ms); maximum QTcF >480 ms; and maximum QTcF >500 ms. LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral). Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    From signature of informed consent until the LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        Maximum QTcF Interval : >450 ms
    1.6
    4.5
        Maximum QTcF Interval : >480 ms
    1.6
    4.5
        Maximum QTcF Interval : >500 ms
    0
    4.5
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Creatinine Clearance (CrCl) at Day 7

    Close Top of page
    End point title
    Percentage of Subjects With Creatinine Clearance (CrCl) at Day 7 [11]
    End point description
    CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of subjects with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    Day 7
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        CrCl: <30mL/min/1.73 m^2
    0
    0
        CrCl: >=30 to <50mL/min/1.73 m^2
    0
    0
        CrCl: >=50 to <80mL/min/1.73 m^2
    0
    0
        CrCl: >=80mL/min/1.73 m^2
    50.8
    59.1
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Creatinine Clearance (CrCl) at End of Intravenous Therapy (EOIV) Visit

    Close Top of page
    End point title
    Percentage of Subjects With Creatinine Clearance (CrCl) at End of Intravenous Therapy (EOIV) Visit [12]
    End point description
    CrCl is a measure of GMFR, an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of subjects with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    EOIV visit (Day 4 up to 16)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        CrCl: <30mL/min/1.73 m^2
    0
    0
        CrCl: >=30 to <50mL/min/1.73 m^2
    0
    0
        CrCl: >=50 to <80mL/min/1.73 m^2
    0
    0
        CrCl: >=80mL/min/1.73 m^2
    82.0
    81.8
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Creatinine Clearance (CrCl) at Test of Cure (TOC) Visit

    Close Top of page
    End point title
    Percentage of Subjects With Creatinine Clearance (CrCl) at Test of Cure (TOC) Visit [13]
    End point description
    CrCl is a measure of GMFR, an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of subjects with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral). Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    TOC is 8 to 15 days after last dose of IV or oral treatment (up to a maximum duration of 50 days)
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        CrCl: <30mL/min/1.73 m^2
    0
    0
        CrCl: >=30 to <50mL/min/1.73 m^2
    0
    0
        CrCl: >=50 to <80mL/min/1.73 m^2
    3.3
    0
        CrCl: >=80mL/min/1.73 m^2
    42.6
    59.1
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Creatinine Clearance (CrCl) at Late Follow-up (LFU) Visit

    Close Top of page
    End point title
    Percentage of Subjects With Creatinine Clearance (CrCl) at Late Follow-up (LFU) Visit [14]
    End point description
    CrCl is a measure of GMFR, an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of subjects with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral). Safety analysis set included all randomized subjects who received any amount of IV study medication.
    End point type
    Primary
    End point timeframe
    LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
    number (not applicable)
        CrCl: <30mL/min/1.73 m^2
    0
    0
        CrCl: >=30 to <50mL/min/1.73 m^2
    0
    0
        CrCl: >=50 to <80mL/min/1.73 m^2
    1.6
    0
        CrCl: >=80mL/min/1.73 m^2
    6.6
    9.1
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Ceftazidime and Avibactam

    Close Top of page
    End point title
    Plasma Concentrations of Ceftazidime and Avibactam [15]
    End point description
    CAZ and AVI pharmacokinetic (PK) parameters derived from population PK analysis. This endpoint was not planned to be analyzed for meropenem receiving cohorts, as pre-specified in protocol. PK analysis set included all subjects who received at least 1 dose of study medication and had atleast 1 CAZ and/ or AVI plasma measurement available. Here, ‘n’ signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    15, 30-90, 300-360 minutes post-dose on Day 3
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Number of subjects analysed
    60
    Units: nanogram per milliliter
    geometric mean (standard deviation)
        Ceftazidime: 15 minute post-dose on Day 3(n= 59)
    63565.5 ± 236761.80
        Ceftazidime: 30-90 minute post-dose on Day 3(n=60)
    38048.0 ± 19810.95
        Ceftazidime:300-360minute post-dose on Day 3(n=60)
    4603.0 ± 10308.96
        Avibactam: 15 minute post-dose on Day 3(n=59)
    12186.2 ± 55720.44
        Avibactam: 30-90 minute post-dose on Day 3(n=60)
    6548.6 ± 4437.55
        Avibactam: 300-360 minute post-dose on Day 3(n=60)
    821.5 ± 1968.21
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Clinical Response (CR) at End of 72 Hours Treatment: Intent-to-treat (ITT) Analysis Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Clinical Response (CR) at End of 72 Hours Treatment: Intent-to-treat (ITT) Analysis Population
    End point description
    Favorable CR was defined as resolution of all acute signs and symptoms of complicated intra- abdominal infection (cIAIs), or improvement to such an extent that no further antimicrobial therapy was required, or improvement but not enough to switch to oral therapy and still on IV study drug at end of 72 hours and had met following criterion: absence of new signs and symptoms, improvement in at least 1 symptom/sign (fever, pain, tenderness, elevated White Blood Cells [WBCs], elevated c-reactive protein) from baseline and no worsening symptom/sign. ITT analysis population included all subjects who had been assigned a randomized treatment.
    End point type
    Secondary
    End point timeframe
    After 72 hours after the start of IV study infusion on Day 1
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
        number (confidence interval 95%)
    93.4 (85.2 to 97.7)
    90.9 (73.9 to 98.1)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Clinical Response (CR) at End of Intravenous Therapy (EOIV) Visit: Intent-to-treat (ITT) Analysis Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Clinical Response (CR) at End of Intravenous Therapy (EOIV) Visit: Intent-to-treat (ITT) Analysis Population
    End point description
    Favorable CR was resolution of all acute signs and symptoms of cIAI or improvement to such an extent that no further antimicrobial therapy was required, or improvement in subjects who had switch to oral therapy and met the following criterion: afebrile (temperature <=38.0°C) for at least 24 hours, absence of new and improvement in at least 1 symptom or sign (fever, pain, tenderness, elevated WBCs, elevated c-reative-protein) from baseline and worsening of none. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. ITT analysis population included all subjects who had been assigned a randomized treatment.
    End point type
    Secondary
    End point timeframe
    EOIV visit (Day 4 up to 16)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
        number (confidence interval 95%)
    96.7 (89.9 to 99.3)
    100 (89.3 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Clinical Response (CR) at End of Treatment (EOT) Visit: Intent-to-treat (ITT) Analysis Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Clinical Response (CR) at End of Treatment (EOT) Visit: Intent-to-treat (ITT) Analysis Population
    End point description
    Favorable CR was resolution of all acute signs and symptoms of cIAI, or improvement to such an extent that no further antimicrobial therapy was required. EOT visit occurred within 48 hours after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study if on oral switch therapy (which occurred within the maximum study treatment duration of 15 days). ITT analysis population included all subjects who had been assigned a randomized treatment.
    End point type
    Secondary
    End point timeframe
    EOT visit (up to a maximum duration of Day 17 [48 hours after maximum study treatment of 15 days])
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
        number (confidence interval 95%)
    91.8 (83.0 to 96.8)
    100 (89.3 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Clinical Response (CR) at Test of Cure (TOC) Visit: Intent-to-treat (ITT) Analysis Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Clinical Response (CR) at Test of Cure (TOC) Visit: Intent-to-treat (ITT) Analysis Population
    End point description
    Favorable CR was resolution of all acute signs and symptoms of cIAI, or improvement to such an extent that no further antimicrobial therapy was required. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral). ITT analysis population included all subjects who had been assigned a randomized treatment.
    End point type
    Secondary
    End point timeframe
    TOC visit (8 to 15 days after last dose of IV or oral treatment; up to a maximum study duration of 50 days)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    61
    22
    Units: percentage of subjects
        number (confidence interval 95%)
    91.8 (83.0 to 96.8)
    95.5 (80.7 to 99.5)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Clinical Response (CR): Clinically Evaluable (CE) Analysis Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Clinical Response (CR): Clinically Evaluable (CE) Analysis Population
    End point description
    Favorable CR: resolution of all acute signs, symptoms of cIAI, or improvement to such an extent that no further antimicrobial therapy required, or improvement in subjects who switch to oral therapy and met following criterion: afebrile (temperature<=38.0°C) for >=24 h, absence of new and improvement in at >= symptom or sign (fever, pain, tenderness, elevated WBCs, elevated c-reative-protein)from baseline and worsening of none. EOIV visit: 24 h after completion of last infusion of study drug. EOT visit occurred within 48 hours after completion of last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study if on oral switch therapy (which occurred within the maximum study treatment duration of 15 days). TOC visit: within 8 to 15 days after last dose of any study drug. CE analysis set. Here, ‘n’= subjects evaluable at specified time points, for each arm respectively.
    End point type
    Secondary
    End point timeframe
    After 72 hours after the start of IV study infusion on Day 1,EOIV(Day4 up to 16),EOT visit(up to a maximum duration of Day17[48h after maximum study treatment of 15days]) and TOC visit(up to a maximum study duration of 50days)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    56
    20
    Units: percentage of subjects
    number (confidence interval 95%)
        At the end 72 hours study medication (n= 49, 20)
    98.0 (90.9 to 99.8)
    95.0 (78.9 to 99.5)
        EOIV (n= 54, 20)
    98.1 (91.7 to 99.8)
    100 (88.3 to 100)
        EOT (n= 52, 20)
    94.2 (85.4 to 98.3)
    100 (88.3 to 100)
        TOC (n= 56, 20)
    92.9 (83.9 to 97.5)
    95.0 (78.9 to 99.5)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Microbiological Response: Microbiological Intent-to-treat (Micro-ITT) Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Microbiological Response: Microbiological Intent-to-treat (Micro-ITT) Population
    End point description
    Favorable microbiological response was achieved when all baseline pathogens were eradicated or presumed eradicated based on investigator's discretion. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral). LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days). Micro-ITT analysis population included all randomized subjects who had a baseline pathogen known to cause cIAI.
    End point type
    Secondary
    End point timeframe
    EOIV visit (Day 4 up to 16), EOT visit (up to a maximum duration of Day 17 [48 hours after maximum study treatment of 15 days]) and TOC visit (up to a maximum study duration of 50 days) and LFU visit
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    50
    19
    Units: percentage of subjects
    number (not applicable)
        EOIV
    96.0
    100
        EOT
    90.0
    100
        TOC
    90.0
    94.7
        LFU
    90.0
    94.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Favorable Microbiological Response: Microbiologically Evaluable (ME) Population

    Close Top of page
    End point title
    Percentage of Subjects With Favorable Microbiological Response: Microbiologically Evaluable (ME) Population
    End point description
    Favorable microbiological response was achieved when all baseline pathogens were eradicated or presumed eradicated based on investigator's discretion.EOIV visit occurred within 24hours after completion of last infusion of the study drug.EOT visit occurred within 48hours after completion of last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study if on oral switch therapy (which occurred within the maximum study treatment duration of 15 days). TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral). LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days). ME analysis population=randomized subjects with cIAI who received study medication for >=48h and clinical failure or clinical failure with treatment limiting AE and subjects with >=72h treatment and favorable microbiological response.‘n’= subjects who were evaluable at specified time points, for each arm respectively.
    End point type
    Secondary
    End point timeframe
    EOIV visit (Day 4 up to 16), EOT visit (up to a maximum duration of Day 17 [48 hours after maximum study treatment of 15 days]), TOC visit (up to a maximum study duration of 50 days) and LFU visit
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    40
    15
    Units: percentage of subjects
    number (not applicable)
        EOIV (n= 40, 15)
    97.5
    100
        EOT (n= 36, 15)
    91.7
    100
        TOC (n= 40, 15)
    90.0
    93.3
        LFU (n= 37, 14)
    89.2
    92.9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinical Relapse at Late Follow-up (LFU) Visit: Clinically Evaluable (CE) Population

    Close Top of page
    End point title
    Percentage of Subjects With Clinical Relapse at Late Follow-up (LFU) Visit: Clinically Evaluable (CE) Population
    End point description
    A subject was said to have clinical relapse if met either 1 of the following criteria: reappearance or worsening of signs and symptoms of cIAI that required further antimicrobial therapy and/or surgery, or death after TOC in which cIAI was contributory. LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral). CE analysis population included randomized subjects with cIAI who received study medication for >=48h and clinical failure or clinical failure with treatment limiting AE and subjects with >=72h treatment and favorable clinicial response. Here, number of subjects analyzed=subjects who were evaluable for this measure.
    End point type
    Secondary
    End point timeframe
    LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    48
    18
    Units: percentage of subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Clinical Relapse at Late Follow-up (LFU) Visit: Microbiologically Evaluable (ME) Population

    Close Top of page
    End point title
    Percentage of Subjects with Clinical Relapse at Late Follow-up (LFU) Visit: Microbiologically Evaluable (ME) Population
    End point description
    A subject was said to have clinical relapse if me either 1 of the following criteria: reappearance or worsening of signs and symptoms of cIAI that required further antimicrobial therapy and/or surgery, or death after TOC in which cIAI was contributory. LFU visit occurred within 27 to 50 days after start of study treatment (IV or oral). ME analysis population included randomized subjects with cIAI who received study medication for >=48h and clinical failure or clinical failure with treatment-limiting AE and subjects with >=72h treatment and favorable microbiological response. Number of subjects analyzed= subjects who were evaluable for this measure.
    End point type
    Secondary
    End point timeframe
    LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    37
    14
    Units: percentage of subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Emergent Infections: Microbiological Intent-to-treat (Micro-ITT) Population

    Close Top of page
    End point title
    Percentage of Subjects With Emergent Infections: Microbiological Intent-to-treat (Micro-ITT) Population
    End point description
    Emergent infections were categorized as super infections and new infections. Superinfection: An intra-abdominal culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. New infection: An intra-abdominal culture identified pathogen other than a baseline pathogen at any time after study treatment had finished along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. Subjects with any (super infections or new infections) of the infections were reported. Subjects with any (super infections or new infections) of the infections were reported. Micro-ITT analysis population included all randomized subjects who had a baseline pathogen known to cause cIAI.
    End point type
    Secondary
    End point timeframe
    Baseline up to 50 days
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    50
    19
    Units: percentage of subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Emergent Infections at Test of Cure (TOC) Visit: Microbiologically Evaluable Population

    Close Top of page
    End point title
    Percentage of Subjects with Emergent Infections at Test of Cure (TOC) Visit: Microbiologically Evaluable Population
    End point description
    Emergent Infections was an intra-abdominal culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy, new infection was an intra-abdominal culture identified pathogen other than a baseline pathogen at any time after study treatment has finished along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral). ME analysis population included randomized subjects with cIAI who received study medication for >=48h and clinical failure or clinical failure with treatment limiting AE,and subjects with >=72h treatment and favorable microbiological response.
    End point type
    Secondary
    End point timeframe
    TOC visit (8 to 15 days after last dose of IV or oral treatment; up to a maximum study duration of 50 days)
    End point values
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole Meropenem
    Number of subjects analysed
    40
    15
    Units: percentage of subjects
    0
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From signature of informed consent until the LFU visit (27 to 50 days after start of study treatment, up to a maximum study duration of 50 days).
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Meropenem
    Reporting group description
    Subjects received 15 to 30 minutes IV infusion of meropenem 20 mg/kg every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.

    Reporting group title
    Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Reporting group description
    Subjects with CrCL >=50 mL/min received 2-hour IV infusion of 2000 mg CAZ/500 mg AVI (subjects with body weight >=40 kg) or 50 mg/kg CAZ/12.5 mg/kg AVI (subjects with body weight <40 kg), followed by 10 mg/kg metronidazole IV infusion over 20 to 30 minutes. Both infusions were administered to subjects every 8 hours for a minimum of 72 hours and up to a maximum duration of 15 days. Dose of CAZ-AVI was reduced to 50 percent, if the CrCl of subject decreased to <=50 mL/min, and subject was removed from study therapy, if CrCl decreased below 30 mL/min. After having 72 hours of IV treatment, subjects had option to switch to an oral therapy at the investigator's discretion.

    Serious adverse events
    Meropenem Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 22 (4.55%)
    5 / 61 (8.20%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Postoperative ileus
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral meatus stenosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Meropenem Ceftazidime- Avibactam (CAZ-AVI) plus Metronidazole
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 22 (27.27%)
    14 / 61 (22.95%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 61 (1.64%)
         occurrences all number
    2
    1
    General disorders and administration site conditions
    Infusion site phlebitis
         subjects affected / exposed
    0 / 22 (0.00%)
    4 / 61 (6.56%)
         occurrences all number
    0
    5
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 61 (0.00%)
         occurrences all number
    2
    0
    Vomiting
         subjects affected / exposed
    2 / 22 (9.09%)
    9 / 61 (14.75%)
         occurrences all number
    2
    9

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Mar 2017
    Added ITT and Micro-ITT analysis sets to the analysis in line with Food and Drug Administration (FDA) feedback; Added description of oral medications table summary; Amended AEs of SI to summarize by topic; Amended approach for summarising laboratory abnormality criteria.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA