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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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 Phase 3, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Plazomicin Compared with Colistin in Patients with Infection due to Carbapenem-Resistant Enterobacteriaceae (CRE)

    Summary
    EudraCT number
    		 2013-001997-18
    Trial protocol
    		 GR   ES   IT   DE   FR  
    Global end of trial date
    15 Sep 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Oct 2017
    First version publication date
    27 Oct 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ACHN-490-007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01970371
    WHO universal trial number (UTN)
    		 U1111-1151-2686
    Sponsors
    Sponsor organisation name
    Achaogen Inc.
    Sponsor organisation address
    1 Tower Pl #300, South San Francisco, United States, 94080
    Public contact
    Clinical Trials Registration Group, Achaogen, Inc., +1 650800-3636, clinical-trials@achaogen.com
    Scientific contact
    Clinical Trials Registration Group, Achaogen, Inc., +1 650800-3636, clinical-trials@achaogen.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
    15 Sep 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Sep 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to demonstrate the superiority, in terms of all-cause mortality at 28 days or significant disease-related complications, of a plazomicin-based regimen compared with a colistin-based regimen in the treatment of BSI or nosocomial pneumonia due to CRE.
    Protection of trial subjects
    This study was conducted in accordance with the US Food and Drug Administration (FDA), ICH E6 Guidelines for Good Clinical Practice, the Declaration of Helsinki (October 1996), and applicable local, state, and national laws. For European Union member states, this includes Directive 2001/20/EC, Directive 205/28/EC, and other directives as applicable, as well as applicable local and national laws.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Sep 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 2 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Greece: 56
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Brazil: 9
    Country: Number of subjects enrolled
    Turkey: 2
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    69
    EEA total number of subjects
    57
    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)
    28
    From 65 to 84 years
    41
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 69 subjects were enrolled in the study.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Plazomicin
    Arm description
    		 Subjects received 15 milligram per killogram (mg/kg) plazomicin therapy (plus meropenem or tigecycline) as a 30-minute intravenous (IV) infusion once daily for 7 to 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Plazomicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    15 milligrams per kilogram (mg/kg) as a 30 minute (a range of 25–50 minutes was permissible) intravenous (IV) infusion once daily. The initial dose and dosing interval were determined based on the baseline renal function. Subsequent plazomicin doses were determined based on therapeutic drug management (TDM).

    Investigational medicinal product name
    Meropenem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Subjects received 2 grams (g) meropenem as a 3 hour IV infusion every 8 hours (q8h).

    Investigational medicinal product name
    Tigecycline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Subjects received tigecycline as a 100 mg IV loading dose followed by 50 mg IV every 12 hours (q12h) as a maintenance dose. The protocol was amended to allow tigecycline to be administered as a 200 mg IV loading dose followed by 100 mg IV q12h.

    Arm title
    		 Cohort 1: Colistin
    Arm description
    		 Subjects received a 5 mg/kg IV loading dose (300 mg maximum) colistin (plus meropenem or tigecycline) followed by a 5 mg/kg/d maintenance dose divided into every 8 hours (q8h) or every 12 hours (q12h) for 7 to 14 days.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Colistin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Subjects received colistin in the form of its IV prodrug, colistimethate sodium (CMS), as a loading dose of colistin base activity (CBA) infused over 60 minutes. Subjects already receiving colistin at the time of enrollment and who had received >=3 doses did not require a loading dose. Colistin dosing was adjusted according to renal function.

    Investigational medicinal product name
    Meropenem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Subjects received 2 grams (g) meropenem as a 3 hour IV infusion every 8 hours (q8h).

    Investigational medicinal product name
    Tigecycline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Subjects received tigecycline as a 100 mg IV loading dose followed by 50 mg IV every 12 hours (q12h) as a maintenance dose. The protocol was amended to allow tigecycline to be administered as a 200 mg IV loading dose followed by 100 mg IV q12h.

    Arm title
    		 Cohort 2: Plazomicin-Based Therapy
    Arm description
    		 Subjects received 15 mg/kg as a 30 minute IV infusion once daily. Bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP) or ventilator associated bacterial pneumonia (VABP) subjects received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. Complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) subjects received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Plazomicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    15 mg/kg as a 30 minute (a range of 25–50 minutes was permissible) IV infusion once daily. The initial dose and dosing interval were determined based on the baseline renal function. Subsequent plazomicin doses were determined based on therapeutic drug management (TDM).

    Number of subjects in period 1
    		Cohort 1: Plazomicin Cohort 1: Colistin Cohort 2: Plazomicin-Based Therapy
    Started
    18
    21
    30
    Completed
    10
    8
    17
    Not completed
    8
    13
    13
         Death
    8
    13
    12
         Lost to follow-up
    -
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Plazomicin
    Reporting group description
    		 Subjects received 15 milligram per killogram (mg/kg) plazomicin therapy (plus meropenem or tigecycline) as a 30-minute intravenous (IV) infusion once daily for 7 to 14 days.

    Reporting group title
    Cohort 1: Colistin
    Reporting group description
    		 Subjects received a 5 mg/kg IV loading dose (300 mg maximum) colistin (plus meropenem or tigecycline) followed by a 5 mg/kg/d maintenance dose divided into every 8 hours (q8h) or every 12 hours (q12h) for 7 to 14 days.

    Reporting group title
    Cohort 2: Plazomicin-Based Therapy
    Reporting group description
    		 Subjects received 15 mg/kg as a 30 minute IV infusion once daily. Bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP) or ventilator associated bacterial pneumonia (VABP) subjects received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. Complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) subjects received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.

    Reporting group values
    		 Cohort 1: Plazomicin Cohort 1: Colistin Cohort 2: Plazomicin-Based Therapy Total
    Number of subjects
    		 18 21 30 69
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 7 9 12 28
        From 65-84 years
    		 11 12 18 41
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.94 ± 13.94 63.29 ± 18.25 62.8 ± 18.15 -
    Gender categorical
    Units: Subjects
        Female
    		 6 11 7 24
        Male
    		 12 10 23 45
    Subject analysis sets

    Subject analysis set title
    Plazomicin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    PK blood samples were collected on Days 1 and 4 (plus or minus 1 calendar day) from all plazomcin-treated patients for the determination of plazomicin plasma concentrations.

    Subject analysis sets values
    		 Plazomicin
    Number of subjects
    48
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    19
        From 65-84 years
    29
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.6 ± 16.57
    Gender categorical
    Units: Subjects
        Female
    13
        Male
    35

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1: Plazomicin
    Reporting group description
    		 Subjects received 15 milligram per killogram (mg/kg) plazomicin therapy (plus meropenem or tigecycline) as a 30-minute intravenous (IV) infusion once daily for 7 to 14 days.

    Reporting group title
    Cohort 1: Colistin
    Reporting group description
    		 Subjects received a 5 mg/kg IV loading dose (300 mg maximum) colistin (plus meropenem or tigecycline) followed by a 5 mg/kg/d maintenance dose divided into every 8 hours (q8h) or every 12 hours (q12h) for 7 to 14 days.

    Reporting group title
    Cohort 2: Plazomicin-Based Therapy
    Reporting group description
    		 Subjects received 15 mg/kg as a 30 minute IV infusion once daily. Bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP) or ventilator associated bacterial pneumonia (VABP) subjects received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. Complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) subjects received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.

    Subject analysis set title
    Plazomicin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    PK blood samples were collected on Days 1 and 4 (plus or minus 1 calendar day) from all plazomcin-treated patients for the determination of plazomicin plasma concentrations.

    Primary: Percentage of Subjects With All Cause Mortality (ACM) at Day 28 or Significant Disease-Related Complication (SDRC) in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With All Cause Mortality (ACM) at Day 28 or Significant Disease-Related Complication (SDRC) in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 [1]
    End point description
    ACM at Day 28: confirmed date of death within 28 days of the first dose of study drug, irrespective of causality. SDRCs for all subjects: presence of 1 or more of the following complications within 7 days of randomisation: new or worsening acute respiratory distress syndrome (ARDS), new lung abscess, new empyema, new onset of septic shock, new Carbapenem Resistant Enterobacteriaceae (CRE) (HABP/VABP subjects only); persistent bacteremia on study Day ≥5 (BSI subjects only). The mMITT population was a subset of the MITT population and included all subjects who received at least 1 dose of study drug and had a CRE pathogen. CRE= meropenem minimum inhibitory concentration (MIC) of >=4 gram per milliliter (g/mL) or meropenem MIC= 2 g/mL and disk diffusion results (<=19 millimetre [mm]) indicating meropenem resistance, isolated from an acceptable study-qualifying baseline blood (BSI subjects) or lower respiratory tract (HABP/VABP subjects) specimen.
    End point type
    Primary
    End point timeframe
    Up to Day 28 for ACM, up to 7 Days for SDRCs in all Subjects, on or after Day 5 for Bloodstream Infection Subjects Only.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin
    Number of subjects analysed
    17
    20
    Units: percentage of subjects
        number (not applicable)
    23.5
    50
    Statistical analysis title
    		 Colistin vs Plazomicin
    Statistical analysis description
    The 2-sided 90% confidence interval (CI) for the difference between groups in Cohort 1 (colistin minus plazomicin) is based on the unconditional exact method.
    Comparison groups
    Cohort 1: Colistin v Cohort 1: Plazomicin
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 1-sided Fisher's exact test
    Parameter type
    		 Difference Estimate
    Point estimate
    26.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 51.2

    Secondary: Percentage of Subjects With All Cause Mortality (ACM) at Day 28 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With All Cause Mortality (ACM) at Day 28 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 [2]
    End point description
    All cause mortality at Day 28: confirmed date of death within 28 days of the first dose of study drug, irrespective of causality. The mMITT population was a subset of MITT population and included all subjects who received at least 1 dose of study drug and had a CRE pathogen. CRE= meropenem MIC of >=4 g/mL or meropenem MIC= 2 g/mL and disk diffusion results (<=19 mm) indicating meropenem resistance, isolated from an acceptable study-qualifying baseline blood (BSI subjects) or lower respiratory tract (HABP/VABP subjects) specimen.
    End point type
    Secondary
    End point timeframe
    Up to Day 28
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin
    Number of subjects analysed
    17
    20
    Units: percentage of subjects
        number (not applicable)
    11.8
    40
    Statistical analysis title
    		 Colistin vs Plazomicin
    Statistical analysis description
    The 2-sided 90% confidence interval (CI) for the difference between groups in Cohort 1 (colistin minus plazomicin) is based on the unconditional exact method.
    Comparison groups
    Cohort 1: Plazomicin v Cohort 1: Colistin
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 1-sided Fisher's exact test
    Parameter type
    		 Difference Estimate
    Point estimate
    28.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 52.5

    Secondary: Percentage of Subjects with Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in Subjects in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects with Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in Subjects in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 [3]
    End point description
    Clinical response was assessed at EOT in all subjects and at TOC for subjects who were a clinical cure or had an indeterminate outcome at the most recent assessment visit. Assessment of clinical response at TOC was not needed for subjects who were a clinical failure at an earlier assessment visit. Clinical outcomes at both EOT and TOC were independently adjudicated by a committee external to the Sponsor who were blinded to treatment assignment. The assessment of clinical response was confounded by comorbidities and the occurrence of additional infections in this high-risk subject population. Thus, adjudicating clinical response of the baseline CRE infection was influenced by confounding signs and symptoms of unrelated infections or conditions. The difficulty assessing clinical responses supports greater reliance on the more objective mortality-based primary endpoint in these critically ill subjects, particularly in an ITT Population analysis.
    End point type
    Secondary
    End point timeframe
    Up to TOC (Day 23)
    Notes
    [3] - 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: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin
    Number of subjects analysed
    17
    20
    Units: percenatge of subjects
    number (not applicable)
        EOT Visit: Clinical Cure
    64.7
    45
        EOT Visit: Clinical Failure
    35.3
    55
        TOC Visit: Clinical Cure
    35.3
    35
        TOC Visit: Clinical Failure
    58.8
    65
        TOC Visit: Indeterminate Response
    5.9
    0
    Statistical analysis title
    		 Colistin vs Plazomicin
    Statistical analysis description
    The 2-sided 90% confidence interval (CI) for the difference in clinical cure percentage at the TOC visit between groups in Cohort 1 (colistin minus plazomicin) is based on the unconditional exact method.
    Comparison groups
    Cohort 1: Plazomicin v Cohort 1: Colistin
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 1-sided Fisher's exact test
    Parameter type
    		 Difference Estimate
    Point estimate
    -0.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -26.9
         upper limit
    		 26.8

    Secondary: Time to Death Through Day 28 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1

    		 Close Top of page
    End point title
    		 Time to Death Through Day 28 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 [4]
    End point description
    Time to death through Day 28 is defined as days from first dose of study drug to death from any cause on or before Day 28. Subjects who were alive at Day 28 were censored on Day 28. Any subject whose survival status was not known at Day 28 was censored on the last known date alive. The mMITT population included all subjects who received at least 1 dose of study drug and had a CRE pathogen. CRE= meropenem minimum inhibitory concentration (MIC) of >=4 gram per milliliter (g/mL) or meropenem MIC= 2 g/mL and disk diffusion results (<=19 millimetre [mm]) indicating meropenem resistance, isolated from an acceptable study-qualifying baseline blood (BSI subjects) or lower respiratory tract (HABP/VABP subjects) specimen.
    End point type
    Secondary
    End point timeframe
    Up to Day 28.
    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: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin
    Number of subjects analysed
    17
    20
    Units: Percentage of Subjects
    number (not applicable)
        Died by Day 28
    11.8
    40
        Censored at 28 days
    88.2
    60
        Censored at <28 days
    0
    0
    Statistical analysis title
    		 Colistin vs Plazomicin
    Statistical analysis description
    The 2-sided 90% confidence interval (CI) for the unadjusted hazard ratio between groups in Cohort 1 (colistin:plazomicin) is based on a Cox proportional hazards regression model.
    Comparison groups
    Cohort 1: Plazomicin v Cohort 1: Colistin
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 1-sided logrank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.97
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 14.61

    Secondary: Percentage of Subjects With All Cause Mortality (ACM) at Day 14 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With All Cause Mortality (ACM) at Day 14 in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 [5]
    End point description
    ACM at Day 14 was defined as a confirmed date of death within 14 days of the first dose of study drug, irrespective of causality. The mMITT population was a subset of MITT population and included all subjects who received at least 1 dose of study drug and had a CRE pathogen. CRE= meropenem MIC of >=4 g/mL or meropenem MIC= 2 g/mL and disk diffusion results (<=19 mm) indicating meropenem resistance, isolated from an acceptable study-qualifying baseline blood (BSI subjects) or lower respiratory tract (HABP/VABP subjects) specimen.
    End point type
    Secondary
    End point timeframe
    Day 14
    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: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin
    Number of subjects analysed
    17
    20
    Units: percentage of subjects
        number (not applicable)
    5.9
    20
    Statistical analysis title
    		 Colistin vs Plazomicin
    Statistical analysis description
    The two-sided 90% confidence interval for the difference between groups in Cohort 1 (colistin minus plazomicin) is based on the unconditional exact method.
    Comparison groups
    Cohort 1: Plazomicin v Cohort 1: Colistin
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 1-sided Fisher's exact test
    Parameter type
    		 Difference estimate
    Point estimate
    14.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 40.3

    Secondary: Percentage of Subjects With Dose Adjustment due to Therapeutic Drug Management (TDM)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Dose Adjustment due to Therapeutic Drug Management (TDM) [6]
    End point description
    After the initial plazomicin dose, subsequent doses were adjusted, as directed, with the use of TDM on Day 1, 4, and 8 as needed. The safety population included all randomised subjects who received any amount of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 14.
    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: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 1: Colistin are not presented here as TDM collection does not apply to and was not collected for subjects in the colistin arm, as only plazomicin levels were measured.
    End point values
    		 Cohort 1: Plazomicin Cohort 2: Plazomicin-Based Therapy
    Number of subjects analysed
    18
    30
    Units: Percentage of Subjects
        number (not applicable)
    77.8
    86.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Adverse Events (AEs)
    End point description
    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered to be drug related. An AE (also referred to as an adverse experience) can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, and it does not imply any judgment about causality. Adverse events also include the exacerbation or worsening of a condition present at screening other than the index infection for which the subject was enrolled in the study. The safety population included all randomised subjects who received any amount of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 67.
    End point values
    		 Cohort 1: Plazomicin Cohort 1: Colistin Cohort 2: Plazomicin-Based Therapy
    Number of subjects analysed
    18
    21
    30
    Units: Percentage of Subjects
        number (not applicable)
    88.9
    100
    86.7
    No statistical analyses for this end point

    Secondary: Plasma Pharmacokinetics (PK): Area Under the Curve from 0 to 24 Hours (AUC 0–24h)

    		 Close Top of page
    End point title
    		 Plasma Pharmacokinetics (PK): Area Under the Curve from 0 to 24 Hours (AUC 0–24h)
    End point description
    PK blood samples were collected on Days 1 and 4 (plus or minus 1 calendar day) from all plazomcin-treated subjects for the determination of plazomicin plasma concentrations. PK population included all subjects who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Days 1 and 4
    End point values
    		 Plazomicin
    Number of subjects analysed
    48
    Units: mg * h/L
        geometric mean (geometric coefficient of variation)
    235 ± 42
    No statistical analyses for this end point

    Secondary: Plasma Pharmacokinetics (PK): Maximum Observed Plasma Drug Concentration (Cmax)

    		 Close Top of page
    End point title
    		 Plasma Pharmacokinetics (PK): Maximum Observed Plasma Drug Concentration (Cmax)
    End point description
    PK blood samples were collected on Days 1 and 4 (plus or minus 1 calendar day) from all plazomcin-treated subjects for the determination of plazomicin plasma concentrations. PK population included all subjects who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Days 1 and 4
    End point values
    		 Plazomicin
    Number of subjects analysed
    48
    Units: mg/L
        geometric mean (geometric coefficient of variation)
    37.1 ± 39.3
    No statistical analyses for this end point

    Secondary: Plasma Pharmacokinetics (PK): Minimum Observed Plasma Drug Concentration (Cmin)

    		 Close Top of page
    End point title
    		 Plasma Pharmacokinetics (PK): Minimum Observed Plasma Drug Concentration (Cmin)
    End point description
    PK blood samples were collected on Days 1 and 4 (plus or minus 1 calendar day) from all plazomcin-treated subjects for the determination of plazomicin plasma concentrations. PK population included all subjects who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Days 1 and 4
    End point values
    		 Plazomicin
    Number of subjects analysed
    48
    Units: mg/L
        geometric mean (geometric coefficient of variation)
    2.1 ± 99.4
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 67
    Adverse event reporting additional description
    The safety population included all randomised subjects who received any amount of intravenous (IV) study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in => 5% of patients, all AEs are reported here, including those occurring in only a single patient.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Cohort 1: Plazomicin
    Reporting group description
    		 Subjects received 15 mg/kg plazomicin as a 30-minute infusion once daily.

    Reporting group title
    Cohort 1: Colistin
    Reporting group description
    		 Subjects received colistin as a 5-mg/kg IV loading dose (300 mg maximum) followed by a 5-mg/kg/d maintenance dose divided into every 8 hours (q8h) or every 12 hours (q12h).

    Reporting group title
    Cohort 2: Plazomicin-Based Therapy
    Reporting group description
    		 Subjects assigned to plazomicin received 15 mg/kg as a 30 minute IV infusion once daily. BSI, HABP or VABP subjects received Plazomicin and any supplemental antibiotic. cUTI or AP subjects received Plazomicin monotherapy only with an option to switch to oral therapy.

    Serious adverse events
    		 Cohort 1: Plazomicin Cohort 1: Colistin Cohort 2: Plazomicin-Based Therapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 18 (50.00%)
    17 / 21 (80.95%)
    20 / 30 (66.67%)
         number of deaths (all causes)
    8
    13
    12
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pneumothorax
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 21 (9.52%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Pneumonitis chemical
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 21 (9.52%)
    4 / 30 (13.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral ischaemia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 18 (11.11%)
    3 / 21 (14.29%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Endocarditis
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis infectious
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal bacteraemia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 18 (0.00%)
    3 / 21 (14.29%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Septic shock
         subjects affected / exposed
    4 / 18 (22.22%)
    5 / 21 (23.81%)
    5 / 30 (16.67%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 3
    0 / 5
    0 / 4
    Urinary tract infection
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    4 / 30 (13.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperosmolar state
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Plazomicin Cohort 1: Colistin Cohort 2: Plazomicin-Based Therapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 18 (72.22%)
    20 / 21 (95.24%)
    22 / 30 (73.33%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    1
    0
    3
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 21 (9.52%)
    0 / 30 (0.00%)
         occurrences all number
    0
    2
    0
    Pleural effusion
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    1
    Pneumothorax
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 21 (9.52%)
    3 / 30 (10.00%)
         occurrences all number
    0
    2
    3
    Depression
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    0
    1
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    0
    2
    Blood creatinine increased
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 21 (9.52%)
    1 / 30 (3.33%)
         occurrences all number
    1
    3
    1
    Blood fibrinogen decreased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    0
    1
    2
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    3
    1
    2
    Extrasystoles
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 18 (22.22%)
    2 / 21 (9.52%)
    1 / 30 (3.33%)
         occurrences all number
    4
    2
    1
    Leukocytosis
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 18 (11.11%)
    2 / 21 (9.52%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    2
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    2
    0
    1
    Diarrhoea
         subjects affected / exposed
    2 / 18 (11.11%)
    2 / 21 (9.52%)
    3 / 30 (10.00%)
         occurrences all number
    2
    2
    3
    Nausea
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    3 / 30 (10.00%)
         occurrences all number
    0
    1
    3
    Vomiting
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 21 (9.52%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    2
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Penile ulceration
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 18 (11.11%)
    4 / 21 (19.05%)
    5 / 30 (16.67%)
         occurrences all number
    2
    4
    5
    Haematuria
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Renal impairment
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    1
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Fungal sepsis
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    0
    1
    Oral fungal infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 21 (9.52%)
    0 / 30 (0.00%)
         occurrences all number
    1
    2
    0
    Sepsis
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    1
    Skin infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Stoma site abscess
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Systemic candida
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Tinea cruris
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    Tracheobronchitis
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences all number
    1
    1
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 21 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    0
    Hypernatraemia
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    1
    1
    2
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 21 (9.52%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 21 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    0
    2
    Hypokalaemia
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    1
    1
    2
    Hypomagnesaemia
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    0 / 30 (0.00%)
         occurrences all number
    1
    1
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    1
    1
    3
    Hypophosphataemia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 21 (4.76%)
    2 / 30 (6.67%)
         occurrences all number
    0
    1
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Mar 2015
    1. Protocol amended to address enrollment changes a. A lower than expected incidence of the study-qualifying infections due to carbapenem resistant Enterobacteriaceae (CRE) b. Challenges in meeting the eligibility criteria due to prolonged turnaround times in microbiology laboratories c. Overly stringent inclusion criteria for the diagnosis of ventilator associated bacterial pneumonia (VABP) d. Burdensome pharmacokinetic (PK) assessments e. Requirement for adjunctive tigecycline to be used at doses lower than the institutional standard of care for serious infections due to CRE f. Complex dose adjustments for plazomicin 2. Primary endpoint was amended to include SDRCs that are more infection attributable than ACM
    13 Jul 2015
    1. Added a second nonrandomized cohort of subjects (Cohort 2) with serious infections that had a high likelihood of being due to CRE but who were excluded from enrollment in the randomized cohort

    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.
    Due to challenges with enrolling the study, it was stopped early and thus, it did not reach the originally planned sample size and was not adequately powered.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 07:34:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA