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    Clinical Trial Results:
    Phase II, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone in Patients with Complicated Urinary Tract Infection

    Summary
    EudraCT number
    		 2011-005707-32
    Trial protocol
    		 ES   GR   LV   BG   PL  
    Global end of trial date
    28 Jul 2015

    Results information
    Results version number
    		 v1
    This version publication date
    16 Jul 2016
    First version publication date
    16 Jul 2016
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    7655-003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01505634
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Registration Number: MK-7655-003
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    28 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a multi-site, randomized, double-blind study to compare the safety and efficacy of 125 mg or 250 mg doses of MK-7655 co-administered with imipenem/cilastatin versus imipenem/cilastatin administered alone in treating complicated urinary tract infection (cUTI) in adults 18 years or older. The primary hypothesis is that MK-7655 co-administered with imipenem/cilastatin is non-inferior to imipenem/cilastatin administered alone with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 54
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    Latvia: 46
    Country: Number of subjects enrolled
    Peru: 21
    Country: Number of subjects enrolled
    Poland: 14
    Country: Number of subjects enrolled
    Romania: 63
    Country: Number of subjects enrolled
    Russian Federation: 6
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Turkey: 27
    Country: Number of subjects enrolled
    Ukraine: 59
    Country: Number of subjects enrolled
    United States: 4
    Worldwide total number of subjects
    302
    EEA total number of subjects
    180
    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)
    180
    From 65 to 84 years
    117
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study enrolled participants with clinically suspected and/or bacteriologically documented cUTI or acute pyelonephritis judged by the investigator to be serious (requiring hospitalization and IV antibiotic therapy); pyuria; and 1 positive urine culture within 48 hours of enrollment. Other inclusion and exclusion criteria applied.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-7655 250 mg with imipenem/cilastatin
    Arm description
    		 MK-7655 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-7655 250 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MK-7655 250 mg IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    imipenem/cilastatin 500 mg
    Investigational medicinal product code
    Other name
    PRIMAXIN®, TIENAM®
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MK-7655 250 mg IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    Ciprofloxacin 500 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg of Ciprofloxacin (as optional oral therapy following minimum duration of IV study drug) twice a day

    Arm title
    		 MK-7655 125 mg with imipenem/cilastatin
    Arm description
    		 MK-7655 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    imipenem/cilastatin 500 mg
    Investigational medicinal product code
    Other name
    PRIMAXIN®, TIENAM®
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MK-7655 125 mg IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    MK-7655 125 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MK-7655 125 mg IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    Ciprofloxacin 500 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg of Ciprofloxacin (as optional oral therapy following minimum duration of IV study drug) twice a day

    Arm title
    		 Placebo for MK-7655 with imipenem/cilastatin
    Arm description
    		 Matching placebo for MK-7655 (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
    Arm type
    		 Placebo

    Investigational medicinal product name
    imipenem/cilastatin 500 mg
    Investigational medicinal product code
    Other name
    PRIMAXIN®, TIENAM®
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Matching placebo for MK-7655 IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    Matching placebo for MK-7655
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Matching placebo for MK-7655 IV co-administered with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours

    Investigational medicinal product name
    Ciprofloxacin 500 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg of Ciprofloxacin (as optional oral therapy following minimum duration of IV study drug) twice a day

    Number of subjects in period 1
    		MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Started
    101
    101
    100
    Treated
    99
    99
    100
    Completed
    92
    91
    95
    Not completed
    9
    10
    5
         Adverse event, serious fatal
    1
    -
    -
         Consent withdrawn by subject
    2
    5
    1
         Physician decision
    1
    1
    -
         Adverse event, non-fatal
    1
    -
    -
         Insufficient supply of drug at site
    1
    -
    -
         Lost to follow-up
    1
    4
    4
         Protocol deviation
    2
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MK-7655 250 mg with imipenem/cilastatin
    Reporting group description
    		 MK-7655 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    MK-7655 125 mg with imipenem/cilastatin
    Reporting group description
    		 MK-7655 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    Placebo for MK-7655 with imipenem/cilastatin
    Reporting group description
    		 Matching placebo for MK-7655 (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin Total
    Number of subjects
    		 101 101 100 302
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 59 64 57 180
        From 65-84 years
    		 39 37 41 117
        85 years and over
    		 3 0 2 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.9 ( 17.3 ) 55.9 ( 17.5 ) 55.7 ( 19.2 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 51 60 42 153
        Male
    		 50 41 58 149

    End points

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    End points reporting groups
    Reporting group title
    MK-7655 250 mg with imipenem/cilastatin
    Reporting group description
    		 MK-7655 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    MK-7655 125 mg with imipenem/cilastatin
    Reporting group description
    		 MK-7655 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    Placebo for MK-7655 with imipenem/cilastatin
    Reporting group description
    		 Matching placebo for MK-7655 (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Primary: Percentage of Participants with a Favorable Microbiological Response at Completion of IV Study Therapy

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    End point title
    		 Percentage of Participants with a Favorable Microbiological Response at Completion of IV Study Therapy
    End point description
    Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as “favorable” if all pathogens isolated from a participant at baseline demonstrated a “favorable” response at the time point evaluated. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Primary
    End point timeframe
    At time of last dose of IV study medication (up to post-randomization day 14)
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    67
    71
    75
    Units: Percentage of Participants
        number (confidence interval 95%)
    95.5 (87.5 to 99.1)
    98.6 (92.4 to 100)
    98.7 (92.8 to 100)
    Statistical analysis title
    		 Percent Difference (Diff) in Favorable MR
    Statistical analysis description
    Non-inferiority for the MK-7655 250 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group was demonstrated if the lower bound of the 95% CI was not lower than the pre-specified non-inferiority margin of -15%.
    Comparison groups
    Placebo for MK-7655 with imipenem/cilastatin v MK-7655 250 mg with imipenem/cilastatin
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.005
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    -3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.2
         upper limit
    		 3.2
    Statistical analysis title
    		 Percent Diff in Favorable MR
    Statistical analysis description
    Non-inferiority for the MK-7655 125 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group was demonstrated if the lower bound of the 95% CI was not lower than the pre-specified non-inferiority margin of -15%.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.001
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 5.9

    Primary: Number of Participants with an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was ≥ 5X the Upper Limit of Normal (ULN)

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    End point title
    		 Number of Participants with an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was ≥ 5X the Upper Limit of Normal (ULN)
    End point description
    All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5X ULN or greater were recorded.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    1
    1
    0
    Statistical analysis title
    		 Percent Diff in Number of ECI #1
    Statistical analysis description
    Event of Clinical Interest (ECI) #1 is a confirmed elevated AST or ALT ≥5X ULN. Inferential testing for statistical significance with p-values and 95% confidence intervals was performed to provide a comparison between the MK-7655 250 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group.
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.315
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 5.5
    Statistical analysis title
    		 Percent Diff in Number of ECI #1
    Statistical analysis description
    Event of Clinical Interest (ECI) #1 is a confirmed elevated AST or ALT ≥5X ULN. Inferential testing for statistical significance with p-values and 95% confidence intervals was performed to provide a comparison between the MK-7655 125 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.315
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 5.5

    Primary: Number of Participants with Elevated AST or ALT Laboratory Values That Were ≥3X the ULN, as Well as Elevated Total Bilirubin ≥2X the ULN, and Alkaline Phosphatase Values <2X the ULN

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    End point title
    		 Number of Participants with Elevated AST or ALT Laboratory Values That Were ≥3X the ULN, as Well as Elevated Total Bilirubin ≥2X the ULN, and Alkaline Phosphatase Values <2X the ULN
    End point description
    All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3X ULN, total bilirubin measurements that were ≥2X ULN and, at the same time, an ALP measurement of < 2X ULN were recorded.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    0
    0
    0
    Statistical analysis title
    		 Percent Diff in Number of ECI #2
    Statistical analysis description
    Event of Clinical Interest (ECI) #2 is elevated AST or ALT ≥3X ULN, elevated total bilirubin ≥2X ULN, and with an ALP <2X ULN. Inferential testing for statistical significance with p-values and 95% confidence intervals was performed to provide a comparison between the MK-7655 250 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group.
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 > 0.999
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 3.8
    Notes
    [1] - There were no participants who met the criteria for ECI #2.
    Statistical analysis title
    		 Percent Diff in Number of ECI #2
    Statistical analysis description
    Event of Clinical Interest (ECI) #2 is elevated AST or ALT ≥3X ULN, elevated total bilirubin ≥2X ULN, and with an ALP <2X ULN. Inferential testing for statistical significance with p-values and 95% confidence intervals was performed to provide a comparison between the MK-7655 125 mg + imipenem/cilastatin group versus the Placebo for MK-7655 + imipenem/cilastatin group.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 > 0.999
    Method
    		 Miettinen and Nurminen Method
    Parameter type
    		 Percent Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 3.8
    Notes
    [2] - There were no participants who met the criteria for ECI #2.

    Primary: Number of Participants with At Least 1 Adverse Event (AE)

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    End point title
    		 Number of Participants with At Least 1 Adverse Event (AE)
    End point description
    AEs were collected on all randomized participants who received ≥1 dose of study treatment. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    28
    29
    30
    Statistical analysis title
    		 Percent Diff in Number of AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.3
         upper limit
    		 10.9
    Statistical analysis title
    		 Percent Diff in Number of AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.4
         upper limit
    		 12

    Primary: Number of Participants with Any Serious Adverse Event (SAE)

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    End point title
    		 Number of Participants with Any Serious Adverse Event (SAE)
    End point description
    SAEs were collected on all randomized participants who received ≥1 dose of study treatment. A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    3
    1
    3
    Statistical analysis title
    		 Percent Diff in Number of SAEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.8
         upper limit
    		 5.9
    Statistical analysis title
    		 Percent Diff in Number of SAEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.6
         upper limit
    		 2.8

    Primary: Number of Participants with Any Drug-related AE

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    End point title
    		 Number of Participants with Any Drug-related AE
    End point description
    Drug-related (DR) AEs were collected on all randomized participants who received ≥1 dose of study treatment. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    10
    9
    9
    Statistical analysis title
    		 Percent Diff in Number of DR AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 9.8
    Statistical analysis title
    		 Percent Diff in Number of DR AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 8.6

    Primary: Number of Participants with Drug-related Serious AEs

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    End point title
    		 Number of Participants with Drug-related Serious AEs
    End point description
    Drug-related SAEs were collected on all randomized participants who received ≥1 dose of study treatment. A serious, drug-related AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    1
    0
    1
    Statistical analysis title
    		 Percent Diff in Number of DR SAEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 4.6
    Statistical analysis title
    		 Percent Diff in Number of DR SAEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 2.8

    Primary: Number of Participants Who Discontinued IV Study Therapy Due to an AE

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    End point title
    		 Number of Participants Who Discontinued IV Study Therapy Due to an AE
    End point description
    The number of participants who had IV therapy stopped due to an AE. Discontinuations (Discons) were reported for all randomized participants who received ≥1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    3
    1
    2
    Statistical analysis title
    		 Percent Diff in Number of Discons Due to AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 3.7
    Statistical analysis title
    		 Percent Diff in Number of Discons Due to AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 6.8

    Primary: Number of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE

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    End point title
    		 Number of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
    End point description
    The number of participants who had IV therapy stopped due to a drug-related AE. Discontinuations were reported for all randomized participants who received ≥1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    2
    1
    1
    Statistical analysis title
    		 Percent Diff in Number of Discons Due to DR AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 6.2
    Statistical analysis title
    		 Percent Diff in Number of Discons Due to DR AEs
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 4.6

    Primary: Number of Participants with Specific AEs, System Organ Class (SOC) or Laboratory Pre-defined Limit of Change (PDLC) with Incidence of ≥4 Participants in One Treatment Group

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    End point title
    		 Number of Participants with Specific AEs, System Organ Class (SOC) or Laboratory Pre-defined Limit of Change (PDLC) with Incidence of ≥4 Participants in One Treatment Group
    End point description
    Analysis includes adverse events and abnormal laboratory values with an incidence of ≥4 participants in one treatment group or system organ class. AEs were collected for all randomized participants who received ≥1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 14 days following completion of all study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    99
    99
    100
    Units: Number of Participants
    28
    29
    30
    Statistical analysis title
    		 Percent Diff in Number of AEs with Rate ≥4
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 250 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.3
         upper limit
    		 10.9
    Statistical analysis title
    		 Percent Diff in Number of AEs with Rate ≥4
    Statistical analysis description
    Difference in percentage and 95% CI are based on unconditional and asymptotic Miettinen and Nurminen method.
    Comparison groups
    MK-7655 125 mg with imipenem/cilastatin v Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.4
         upper limit
    		 12

    Secondary: Percentage of Participants with a Favorable Microbiological Response at Completion of IV Study Therapy Who Have Imipenem-resistant, Gram-negative cUTI Infections

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    End point title
    		 Percentage of Participants with a Favorable Microbiological Response at Completion of IV Study Therapy Who Have Imipenem-resistant, Gram-negative cUTI Infections
    End point description
    Microbiological response was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for imipenem-resistant gram-negative or anaerobic infections at baseline. The overall microbiological response was determined as “favorable” if all pathogens isolated from a participant at baseline demonstrated a “favorable” response at the time point evaluated. The analysis included all participants in the ME population with imipenem-resistant gram-negative infections at baseline.
    End point type
    Secondary
    End point timeframe
    At time of last dose of IV study medication (up to post-randomization day 14)
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    10
    7
    6
    Units: Percentage of Participants
        number (confidence interval 95%)
    100 (69.2 to 100)
    100 (59 to 100)
    100 (54.1 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Favorable Microbiological Response at Early Follow-up

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    End point title
    		 Percentage of Participants with a Favorable Microbiological Response at Early Follow-up
    End point description
    Microbiological response was assessed based on results of bacterial cultures obtained up to 9 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as “favorable” if all pathogens isolated from a participant at baseline demonstrated a “favorable” response at the time point evaluated. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Secondary
    End point timeframe
    Up to 9 days following completion of all IV and oral study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    65
    72
    71
    Units: Percentage of Participants
        number (confidence interval 95%)
    61.5 (48.6 to 73.3)
    68.1 (56 to 78.6)
    70.4 (58.4 to 80.7)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Favorable Clinical Response at Completion of IV Study Therapy

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    End point title
    		 Percentage of Participants with a Favorable Clinical Response at Completion of IV Study Therapy
    End point description
    Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Secondary
    End point timeframe
    At time of last dose of IV study medication (up to post-randomization day 14)
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    69
    78
    80
    Units: Percentage of Participants
        number (confidence interval 95%)
    97.1 (89.9 to 99.6)
    98.7 (93.1 to 100)
    98.8 (93.2 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Favorable Clinical Response at Early Follow-up

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    End point title
    		 Percentage of Participants with a Favorable Clinical Response at Early Follow-up
    End point description
    Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Secondary
    End point timeframe
    Up to 9 days following completion of all IV and oral study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    64
    73
    76
    Units: Percentage of Participants
        number (confidence interval 95%)
    89.1 (78.8 to 95.5)
    91.8 (83 to 96.9)
    93.4 (85.3 to 97.8)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Favorable Clinical Response at Late Follow-up

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    End point title
    		 Percentage of Participants with a Favorable Clinical Response at Late Follow-up
    End point description
    Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Secondary
    End point timeframe
    Up to 42 days following completion of all IV and oral study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    62
    71
    76
    Units: Percentage of Participants
        number (confidence interval 95%)
    88.7 (78.1 to 95.3)
    87.3 (77.3 to 94)
    88.2 (78.7 to 94.4)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Favorable Microbiological Response at Late Follow-up

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    End point title
    		 Percentage of Participants with a Favorable Microbiological Response at Late Follow-up
    End point description
    Microbiological response was assessed based on results of bacterial cultures obtained up to 42 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as “favorable” if all pathogens isolated from a participant at baseline demonstrated a “favorable” response at the time point evaluated. The analysis included all participants in the ME population with non-missing/non-indeterminate response.
    End point type
    Secondary
    End point timeframe
    Up to 42 days following completion of all IV and oral study medication
    End point values
    		 MK-7655 250 mg with imipenem/cilastatin MK-7655 125 mg with imipenem/cilastatin Placebo for MK-7655 with imipenem/cilastatin
    Number of subjects analysed
    63
    69
    72
    Units: Percentage of Participants
        number (confidence interval 95%)
    68.3 (55.3 to 79.4)
    65.2 (52.8 to 76.3)
    62.5 (50.3 to 73.6)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 42 days following completion of all study therapy for drug-related serious adverse events and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events
    Adverse event reporting additional description
    AEs were reported for the All Participants as Treated Population that included all randomized participants who received ≥ 1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    MK-7655 250 mg + imipenem/cilastatin
    Reporting group description
    		 MK-7655 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    Placebo + imipenem/cilastatin
    Reporting group description
    		 Matching placebo for MK-7655 (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Reporting group title
    MK-7655 125 mg + imipenem/cilastatin
    Reporting group description
    		 MK-7655 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.

    Serious adverse events
    		 MK-7655 250 mg + imipenem/cilastatin Placebo + imipenem/cilastatin MK-7655 125 mg + imipenem/cilastatin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 99 (5.05%)
    3 / 100 (3.00%)
    2 / 99 (2.02%)
         number of deaths (all causes)
    2
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal cancer
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Renal neoplasm
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Injury, poisoning and procedural complications
    Postoperative wound complication
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 100 (0.00%)
    1 / 99 (1.01%)
         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 disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 99 (1.01%)
    1 / 100 (1.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Intestinal obstruction
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 100 (1.00%)
    0 / 99 (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
    Renal and urinary disorders
    Glomerulonephritis rapidly progressive
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 100 (1.00%)
    0 / 99 (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
    Infections and infestations
    Peritonitis
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Pyelonephritis acute
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 100 (0.00%)
    0 / 99 (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
    Urosepsis
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 100 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         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
    		 MK-7655 250 mg + imipenem/cilastatin Placebo + imipenem/cilastatin MK-7655 125 mg + imipenem/cilastatin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 99 (11.11%)
    7 / 100 (7.00%)
    9 / 99 (9.09%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 99 (7.07%)
    4 / 100 (4.00%)
    3 / 99 (3.03%)
         occurrences all number
    7
    4
    3
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 99 (4.04%)
    4 / 100 (4.00%)
    6 / 99 (6.06%)
         occurrences all number
    4
    5
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Oct 2012
    Protocol Amendment 3 modified the initial inclusion criterion that allowed for inclusion of patients in the study with risk factors for infection with an antibacterial-resistant organism. Additional risk factors for inclusion of these patients were added in this amendment.
    13 May 2014
    Protocol Amendment 5 removed the inclusion criteria that allowed for participants in the study based on at least one of three risk factors for infection with an antibacterial-resistant organism.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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