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    Clinical Trial Results:
    A multi-center, randomized, double-blind study to compare the efficacy and safety of cadazolid versus vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD)

    Summary
    EudraCT number
    2013-002508-15
    Trial protocol
    CZ   BE   HU   SK   GR   HR  
    Global end of trial date
    02 May 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    13 May 2018
    First version publication date
    13 May 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AC-061A302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01983683
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Actelion Pharmaceuticals Ltd
    Sponsor organisation address
    Gewerbestrasse 16, Allschwil, Switzerland, 4123
    Public contact
    clinical trial disclosure desk, Actelion Pharmaceuticals Ltd, clinical-trials-disclosure@its.jnj.com
    Scientific contact
    clinical trial disclosure desk, Actelion Pharmaceuticals Ltd, clinical-trials-disclosure@its.jnj.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
    13 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 May 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine whether the clinical response after 10-day oral administration of cadazolid is non-inferior to oral vancomycin in subjects with CDAD.
    Protection of trial subjects
    The clinical trial was designed and conducted in accordance with the ICH Harmonized Tripartite Guidelines for GCP, with applicable local regulations, including the European Directive 2001/20/EC, the US CFR Title 21 (adapt to the countries where the trial was conducted), and with the ethical principles laid down in the Declaration of Helsinki
    Background therapy
    -
    Evidence for comparator
    The comparator, vancomycin, is approved in Europe and in the US for the treatment of mild–moderate CDAD
    Actual start date of recruitment
    13 Dec 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 220
    Country: Number of subjects enrolled
    Canada: 31
    Country: Number of subjects enrolled
    Belgium: 14
    Country: Number of subjects enrolled
    Croatia: 17
    Country: Number of subjects enrolled
    Czech Republic: 44
    Country: Number of subjects enrolled
    Greece: 47
    Country: Number of subjects enrolled
    Hungary: 33
    Country: Number of subjects enrolled
    Romania: 89
    Country: Number of subjects enrolled
    Slovakia: 2
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Brazil: 37
    Country: Number of subjects enrolled
    Chile: 8
    Country: Number of subjects enrolled
    Israel: 43
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Worldwide total number of subjects
    609
    EEA total number of subjects
    246
    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)
    301
    From 65 to 84 years
    308
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    1128 patients at 105 sites in 15 countries were screened, among whom 631 were randomized at 96 sites in 14 countries worldwide.

    Pre-assignment
    Screening details
    Among the 631 subjects randomized, 22 were excluded from all the analyses due to potential data integrity issues resulting in 609 total participants considered for the analyses. From the 22 excluded patients no serious adverse events (AEs) or study drug discontinuation information were reported. All reported AEs were mild or moderate in intensity.

    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, Carer, Assessor
    Blinding implementation details
    The sponsor staff (except Global Drug Safety in case of SUSAR) and CRO staff (except people responsible for safety report distribution or for bioanalytical analyses of cadazolid) remained blinded to the treatment until unblinding after study closure

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cadazolid
    Arm description
    Subjects with Clostridium difficile-associated diarrhea (CDAD) received oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times a day (qid) for 10 days. Subjects were followed up for 30 days after the last dose of cadazolid. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)
    Arm type
    Experimental

    Investigational medicinal product name
    Cadazolid
    Investigational medicinal product code
    ACT-179811
    Other name
    Pharmaceutical forms
    Granules for oral solution in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Granules to be reconstituted as a suspension prior to oral administration, supplied at a dose of 250 mg

    Investigational medicinal product name
    Vancomycin-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsule identical to vancomycin-capsule but without active substance

    Arm title
    Vancomycin
    Arm description
    Subjects with CDAD received oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days. Subjects were followed up for 30 day after the last dose of vancomycin. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)
    Arm type
    Active comparator

    Investigational medicinal product name
    Vancomycin
    Investigational medicinal product code
    Other name
    Vancocin®
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Each capsule contains 125 mg of vancomycin

    Investigational medicinal product name
    Cadazolid-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules for oral suspension in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Granules without active substance, to be reconstituted as a suspension prior to oral administration

    Number of subjects in period 1
    Cadazolid Vancomycin
    Started
    298
    311
    Completed
    260
    260
    Not completed
    38
    51
         Physician decision
    8
    9
         Adverse event, serious fatal
    11
    15
         Consent withdrawn by subject
    14
    18
         Sponsor Decision
    1
    1
         Lost to follow-up
    4
    8

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cadazolid
    Reporting group description
    Subjects with Clostridium difficile-associated diarrhea (CDAD) received oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times a day (qid) for 10 days. Subjects were followed up for 30 days after the last dose of cadazolid. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)

    Reporting group title
    Vancomycin
    Reporting group description
    Subjects with CDAD received oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days. Subjects were followed up for 30 day after the last dose of vancomycin. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)

    Reporting group values
    Cadazolid Vancomycin Total
    Number of subjects
    298 311 609
    Age categorical
    Units: Subjects
        18-64 years
    143 158 301
        65-74 years
    66 61 127
        75 years and older
    89 92 181
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61.8 ± 18.6 62.0 ± 17.9 -
    Gender categorical
    Units: Subjects
        Female
    194 189 383
        Male
    104 122 226

    End points

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    End points reporting groups
    Reporting group title
    Cadazolid
    Reporting group description
    Subjects with Clostridium difficile-associated diarrhea (CDAD) received oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times a day (qid) for 10 days. Subjects were followed up for 30 days after the last dose of cadazolid. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)

    Reporting group title
    Vancomycin
    Reporting group description
    Subjects with CDAD received oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days. Subjects were followed up for 30 day after the last dose of vancomycin. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)

    Subject analysis set title
    Modified intent-to-treat set (mITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All randomized subjects who have received at least one dose of study treatment and had a confirmed diagnosis of CDAD

    Subject analysis set title
    Per protocol set (PPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    All subjects from the mITT and without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.

    Subject analysis set title
    Safety set (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All randomized subjects who received at least one dose of study treatment and analyzed based on the actual treatment received

    Primary: Clinical Cure Rate (CCR) in the modified intent-to-treat population

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    End point title
    Clinical Cure Rate (CCR) in the modified intent-to-treat population
    End point description
    Clinical Cure is defined as: • Resolution of Diarrhea (ROD) (≤ 3 unformed bowel movement (UBM) per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant (FMT) between first dose of study drug and 2 days after EOT (inclusive). CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
    End point type
    Primary
    End point timeframe
    Up to Day 12 on average (end-of-treatment + 2 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    290
    301
    Units: Percentage of participants
    number (confidence interval 95%)
        Percentage of participants
    81 (76.1 to 85.1)
    85.7 (81.3 to 89.2)
    Statistical analysis title
    Main analysis
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    -4.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.7
         upper limit
    1.3
    Notes
    [1] - Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10. CIs are estimated using the Wilson's score method.
    Statistical analysis title
    Sensitivity analysis
    Statistical analysis description
    Sensitivity analysis with imputation for a single day with missing UBM data between one day before end-of-treatment (EOT) and 2 days after EOT
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    -3.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.6
         upper limit
    2.3
    Notes
    [2] - Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10%. CIs are estimated using the Wilson's score method.

    Primary: Clinical Cure Rate (CCR) in the per-protocol population

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    End point title
    Clinical Cure Rate (CCR) in the per-protocol population
    End point description
    Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.
    End point type
    Primary
    End point timeframe
    Up to Day 12 on average (end-of-treatment + 2 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    247
    259
    Units: Percentage of participants
    number (confidence interval 95%)
        Percentage of participants
    86.6 (81.8 to 90.3)
    91.5 (87.5 to 94.3)
    Statistical analysis title
    Main analysis
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    -4.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.4
         upper limit
    0.6
    Notes
    [3] - Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10%. CIs are estimated using the Wilson's score method.

    Secondary: Sustained Cure Rate (SCR) in the modified intent-to-treat population

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    End point title
    Sustained Cure Rate (SCR) in the modified intent-to-treat population
    End point description
    Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The main analysis is performed on the modified intent-to-treat set (mITT).
    End point type
    Secondary
    End point timeframe
    Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    290
    301
    Units: Percentage of subjects
    number (confidence interval 95%)
        Percentage of subjects
    63.4 (57.8 to 68.8)
    61.8 (56.2 to 67.1)
    Statistical analysis title
    Main analysis
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.1
         upper limit
    9.4
    Notes
    [4] - Superiority of cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above zero. CIs are estimated using the Wilson's score method.

    Secondary: Kaplan-Meier estimates for resolution of diarrhea

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    End point title
    Kaplan-Meier estimates for resolution of diarrhea
    End point description
    Resolution of Diarrhea (ROD) is defined as no more than 3 unformed bowel movements per day for at least two consecutive days for subjects on study treatment. The Kaplan-Meier estimates (KM estimates) for having an event (ROD) are reported for each time point.
    End point type
    Secondary
    End point timeframe
    Up to Day 10
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    290
    301
    Units: KM estimate (% subjects with ROD)
    number (confidence interval 95%)
        Day 1
    51.0 (45.4 to 56.9)
    45.8 (40.4 to 51.6)
        Day 2
    64.5 (59.0 to 70.0)
    59.8 (54.3 to 65.4)
        Day 3
    69.7 (64.3 to 74.8)
    67.8 (62.5 to 73.0)
        Day 4
    73.8 (68.6 to 78.7)
    72.8 (67.6 to 77.7)
        Day 5
    77.9 (73.0 to 82.5)
    78.4 (73.6 to 82.9)
        Day 6
    77.9 (73.0 to 82.5)
    81.4 (76.8 to 85.6)
        Day 7
    79.7 (74.8 to 84.1)
    83.7 (79.3 to 87.6)
        Day 8
    81.0 (76.3 to 85.3)
    85.7 (81.5 to 89.4)
        Day 9
    81.0 (76.3 to 85.3)
    85.7 (81.5 to 89.4)
        Day 10
    81.0 (76.3 to 85.3)
    85.7 (81.5 to 89.4)
    Statistical analysis title
    Main analysis
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7794 [5]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.86
         upper limit
    1.24
    Notes
    [5] - two-sided p-value (alpha 5%) based on log-rank test stratified by first occurrence / first recurrence and geographical region.

    Secondary: Change from baseline to Day 3 in Clostridium difficile infection (CDI) daily symptoms Patient-Reported Outcome (CDI-DaySyms PRO) domain scores

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    End point title
    Change from baseline to Day 3 in Clostridium difficile infection (CDI) daily symptoms Patient-Reported Outcome (CDI-DaySyms PRO) domain scores
    End point description
    CDI-DaySyms PRO is a questionnaire assessing 10 symptoms relevant to subjects with CDAD and grouped into 3 domains: Diarrhea symptoms, Abdominal symptoms and Systemic/Other. The subjects rate the severity of each item as None, Mild, Moderate, Severe or Very severe, converted to numeric scores from 0 to 4, respectively. The daily domain score is calculated as the mean of the non-missing responses for that domain on that day. A negative value for change from baseline corresponds to an improvement in domain score. The three domains are evaluated in a hierarchical manner, starting with Diarrhea Symptoms, then Abdominal Symptoms, and finally Systemic/Other Symptoms. population used: All subjects from the mITT, excluding those who participated in the validation sub-study. No imputation of missing scores was performed prior to deriving response status. Subjects with missing values at baseline or at Day 3 were considered to be non-responders.
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment (10 days after starting study drug) + 2 days
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    232
    245
    Units: Scores on a scale
    number (confidence interval 95%)
        Diarrhea symptoms
    -1.242 (-1.40 to -1.09)
    -1.199 (-1.35 to -1.05)
        Abdominal symptoms
    -0.669 (-0.79 to -0.54)
    -0.693 (-0.82 to -0.57)
        Other symptoms
    -0.670 (-0.77 to -0.56)
    -0.731 (-0.83 to -0.63)
    Statistical analysis title
    Comparison of the diarrhea domain scores
    Statistical analysis description
    ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12. The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements.
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    477
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.6871 [6]
    Method
    ANOVA
    Parameter type
    Least square means difference
    Point estimate
    -0.044
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    0.17
    Notes
    [6] - Two-sided 5% alpha level was used
    Statistical analysis title
    Comparison of the abdominal symptoms domain scores
    Statistical analysis description
    ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12. The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements.
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    477
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7833 [7]
    Method
    ANOVA
    Parameter type
    Least Square Mean difference
    Point estimate
    0.025
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    0.2
    Notes
    [7] - Two-sided 5% alpha level was used
    Statistical analysis title
    Comparison of the other symptoms domain scores
    Statistical analysis description
    ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12. The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements.
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    477
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4145 [8]
    Method
    ANOVA
    Parameter type
    Least Square Mean difference
    Point estimate
    0.061
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.09
         upper limit
    0.21
    Notes
    [8] - Two-sided 5% alpha level was used

    Other pre-specified: Investigator's assessment of clinical response (ICR) rate at Visit 4 in the modified intent-to-treat population

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    End point title
    Investigator's assessment of clinical response (ICR) rate at Visit 4 in the modified intent-to-treat population
    End point description
    ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
    End point type
    Other pre-specified
    End point timeframe
    Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    290
    301
    Units: Percentage of participants
        number (confidence interval 95%)
    87.2 (82.9 to 90.6)
    88.4 (84.3 to 91.5)
    Statistical analysis title
    Exploratory analysis
    Comparison groups
    Cadazolid v Vancomycin
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.5
         upper limit
    4.2

    Other pre-specified: Investigator's assessment of clinical response (ICR) rate at Visit 4 in the per-protocol population

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    End point title
    Investigator's assessment of clinical response (ICR) rate at Visit 4 in the per-protocol population
    End point description
    ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. ICR rate (%) is the percentage of subjects with ICR assessed as cured. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.
    End point type
    Other pre-specified
    End point timeframe
    Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    247
    259
    Units: Percentage of participants
        number (confidence interval 95%)
    91.1 (86.9 to 94.0)
    92.7 (88.8 to 95.3)
    Statistical analysis title
    Exploratory analysis
    Comparison groups
    Vancomycin v Cadazolid
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.5
         upper limit
    3.3

    Other pre-specified: Investigator's assessment of sustained response rate (ISR rate) at Visit 5

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    End point title
    Investigator's assessment of sustained response rate (ISR rate) at Visit 5
    End point description
    ISR rate (%) is the percentage of subjects assessed as Sustained Cure at Visit 5, according to the investigator's own judgement. Sustained Cure is defined for each subject having Clinical Cure and no recurrence. Subjects with missing assessment are considered as having ‘Not Sustained Cure’ for the analysis. ISR rate is used as a supportive measure of the secondary efficacy endpoint (SCR). Analyses are performed on the modified intent-to-treat set (mITT).
    End point type
    Other pre-specified
    End point timeframe
    Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    290
    301
    Units: Percentage of participants
        number (confidence interval 95%)
    69.3 (63.8 to 74.3)
    60.5 (54.8 to 65.8)
    Statistical analysis title
    Exploratory analysis
    Comparison groups
    Vancomycin v Cadazolid
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    8.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.1
         upper limit
    16.4

    Other pre-specified: Sustained Cure Rate (SCR) in the per-protocol population

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    End point title
    Sustained Cure Rate (SCR) in the per-protocol population
    End point description
    Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The analyses performed on the modified intent-to- treat set (mITT) are repeated on the per-protocol set (PPS) for sensitivity.
    End point type
    Other pre-specified
    End point timeframe
    Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    247
    259
    Units: Percentage of participants
        number (confidence interval 95%)
    67.6 (61.5 to 73.1)
    64.9 (58.9 to 70.4)
    Statistical analysis title
    Sensitivity analysis
    Comparison groups
    Vancomycin v Cadazolid
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference between 2 proportions
    Point estimate
    2.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.5
         upper limit
    10.9

    Other pre-specified: Recurrence rate

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    End point title
    Recurrence rate
    End point description
    Recurrence is defined as the occurrence of a new episode of diarrhea (> 3 unformed bowel movements on any day between end-of-treatment + 3 days and end-of-treatment + 30 days ) Recurrence rates is the percentage of subjects assessed as having a recurrence out of subjects with Clinical Cure.
    End point type
    Other pre-specified
    End point timeframe
    Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days)
    End point values
    Cadazolid Vancomycin
    Number of subjects analysed
    235
    258
    Units: Percentage of participants
        number (confidence interval 95%)
    15.7 (11.6 to 20.9)
    17.8 (13.6 to 23.0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious and frequent adverse events are reported from study treatment initiation up to Day 17 on average (i.e., 7 days after EOT or study withdrawal) and all-cause mortality up to Day 40 on average (i.e. 28 to 32 days after EOT on average)
    Adverse event reporting additional description
    294 subjects who received at least one dose of cadazolid (cadazolid arm) and 307 subjects who received at least one dose of vancomycin (vancomycin arm) were included in the safety analysis. The median duration of treatment was 10 days in both arms.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    Cadazolid
    Reporting group description
    Subjects who received oral cadazolid 250 mg twice daily (bid) for 10 days on average

    Reporting group title
    Vancomycin
    Reporting group description
    Subjects who received oral vancomycin 125 mg 4 times per day (qid) for 10 days on average

    Serious adverse events
    Cadazolid Vancomycin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    35 / 294 (11.90%)
    46 / 307 (14.98%)
         number of deaths (all causes)
    11
    15
         number of deaths resulting from adverse events
    Vascular disorders
    Hypovolaemic shock
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 294 (0.34%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rectal cancer
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contrast media reaction
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia test positive
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Porphyria acute
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 294 (0.00%)
    2 / 307 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Acute respiratory failure
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 294 (0.68%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis haemorrhagic
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 294 (0.68%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Chronic kidney disease
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis fungal
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    2 / 294 (0.68%)
    2 / 307 (0.65%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    5 / 294 (1.70%)
    11 / 307 (3.58%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterobacter sepsis
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex hepatitis
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 294 (0.34%)
    4 / 307 (1.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    4 / 294 (1.36%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 294 (0.00%)
    1 / 307 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Transplant abscess
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 294 (0.00%)
    4 / 307 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 294 (0.34%)
    0 / 307 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cadazolid Vancomycin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 294 (15.99%)
    51 / 307 (16.61%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    13 / 294 (4.42%)
    18 / 307 (5.86%)
         occurrences all number
    15
    21
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    15 / 294 (5.10%)
    11 / 307 (3.58%)
         occurrences all number
    20
    12
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    16 / 294 (5.44%)
    11 / 307 (3.58%)
         occurrences all number
    19
    13
    Infections and infestations
    Clostridium difficile infection
         subjects affected / exposed
    10 / 294 (3.40%)
    17 / 307 (5.54%)
         occurrences all number
    11
    17

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Dec 2014
    Main reason for amendment: the main analysis of the primary endpoint (Clinical Cure) initially planned to be performed on the per-protocol population will be conducted on both the modified Intent-to-Treat and Per Protocol populations. Further changes include the addition of an emerging hypervirulent Clostridium difficile strain, the addition of endpoints related to susceptibility testing of C. difficile and vancomycin-resistant enterococci, and general clarifications of eligibility criteria and statistical analyses including a modification to the definition of recurrence for analyses of secondary variable sustained cure rate.
    22 Oct 2015
    Main reason: To remove the interim analysis originally planned after the randomization of 67% of the subjects.

    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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