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    Clinical Trial Results:
    A randomised, controlled, open-label phase III clinical trial in patients with recurrent Clostridioides difficile (CD) infection, to evaluate the efficacy and safety of capsules of lyophilised faecal microbiota vs fidaxomicin

    Summary
    EudraCT number
    		 2020-004591-17
    Trial protocol
    		 ES  
    Global end of trial date
    15 Nov 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Feb 2025
    First version publication date
    12 Feb 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ICD-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05201079
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Mikrobiomik Healthcare Company S.L.
    Sponsor organisation address
    Astondo Bidea, building 612, Derio, Spain, 48160
    Public contact
    Clinical trials, Mikrobiomik Healthcare Company S.L., ensayosclinicos@mikrobiomik.net
    Scientific contact
    Clinical trials, Mikrobiomik Healthcare Company S.L., ensayosclinicos@mikrobiomik.net
    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
    09 Jan 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Nov 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main purpose of the study is to evaluate the efficacy of the investigational medicinal product (MBK-01) compared to the control medication (fidaxomicin), 8 weeks after the treatment completion.
    Protection of trial subjects
    Regarding the lack of efficacy, patients with a new recurrence of Clostridioides difficile infection were withdrawn from the study and treated with rescue medication (vancomycin or fidaxomicin). All patients who dropped out of the study and/or were discontinued before the end of the planned follow-up had an end-of-study visit ≥ 30 days after initiation of treatment, in which at least the relevant information for safety assessment (adverse events and concomitant treatments) was collected.
    Background therapy
    		 Therapeutic support measures were allowed as deemed most appropriate (e.g., hydration-control of the patient's electrolytes and antipyretics in case of fever (>38°C) and as deemed appropriate by the treating medical team).
    Evidence for comparator
    		 Fidaxomicin is the treatment of choice for primary episodes of Clostridiodes difficile infection (CDI), first recurrences, high risk of recurrence and multiple recurrences of CDI by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The Infectious Diseases Society of America (IDSA) recommends both vancomycin and fidaxomicin as the initial treatment for CDI, and fidaxomicin as the treatment of choice for patients with CDI with a high risk of recurrences. European and Spanish expert groups recommend fidaxomicin for critically ill patients, for immunosuppressed patients, and for patients with chronic kidney failure, undergoing transplantation or cancer.
    Actual start date of recruitment
    29 Oct 2021
    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
    Spain: 92
    Worldwide total number of subjects
    92
    EEA total number of subjects
    92
    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)
    42
    From 65 to 84 years
    39
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    		 The inclusion of the first patient was on 29 October 2021. The inclusion of the last patient was on 6 October 2023 (end of recruitment). All patients were recruited in sites in Spain.

    Pre-assignment
    Screening details
    		 Screening period: within 24h after informed consent, patients were evaluated for study eligibility. Participants were tested to determine if they met all the inclusion criteria and none of the exclusion criteria. 93 patients were screened in the study. 1 of them was a screening failure and only 92 were finally included in the study.

    Pre-assignment period milestones
    Number of subjects started
    		 93 [1]
    Number of subjects completed
    		 92

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screening failure: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 93 patients were intially included in the study. 1 of these patients was a selection failure and there is no available data for this patient. Therefore, 92 patients completed the screening period and were randomised to any of the two treatment groups.
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    There are no bliding techniques in this study, as it is an open-label study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MBK-01
    Arm description
    		 Patients randomized to MBK-01 received a single dose of 4 oral capsules of MBK-01.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MBK-01
    Investigational medicinal product code
    Other name
    Heterologous gut microbiota from healthy donors
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received 4 capsules of MBK-01 in a single dose (≥2.1-2.5 x 10^11 microorganisms) after being randomized. If patients had been treated with antibiotic they had to undergo a 24 hours washout period before randomization.

    Arm title
    		 Fidaxomicin
    Arm description
    		 Patients randomized to fidaxomicin received treatment with oral fidaxomicin 200mg/12h for 10 days
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fidaxomicin
    Investigational medicinal product code
    Other name
    Dificlir
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received an oral dose of 200 mg (one tablet) of fidaxomicin twice a day (every 12 hours) for 10 days since randomization. If patients had been treated with antibiotic they had to undergo a 24 hours washout period before randomization.

    Number of subjects in period 1
    		MBK-01 Fidaxomicin
    Started
    45
    47
    Completed
    23
    25
    Not completed
    22
    22
         Physician decision
    1
    1
         Consent withdrawn by subject
    1
    -
         Transfer to other hospital
    -
    1
         Death
    1
    1
         Clinical conditions
    1
    -
         Forbidden medication
    9
    5
         Adverse event
    7
    11
         Serious adverse event and sepsis
    1
    -
         Lost to follow-up
    -
    1
         Ineffective treatment
    -
    2
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MBK-01
    Reporting group description
    		 Patients randomized to MBK-01 received a single dose of 4 oral capsules of MBK-01.

    Reporting group title
    Fidaxomicin
    Reporting group description
    		 Patients randomized to fidaxomicin received treatment with oral fidaxomicin 200mg/12h for 10 days

    Reporting group values
    		 MBK-01 Fidaxomicin Total
    Number of subjects
    		 45 47 92
    Age categorical
    Age was calculated as the difference in years between the date of signing the informed consent form and the date of birth.
    Units: Subjects
        Adults (18-64 years)
    		 18 24 42
        From 65-84 years
    		 21 18 39
        85 years and over
    		 6 5 11
    Age continuous
    Age was calculated as the difference in years between the date of signing the informed consent form and the date of birth.
    Units: years
        arithmetic mean (standard deviation)
    		 65.22 ( 17.24 ) 65.26 ( 14.65 ) -
    Gender categorical
    Units: Subjects
        Female
    		 30 30 60
        Male
    		 15 17 32
    Type of Clostridioides difficile infection episode
    A primary episode would be the first episode of Clostridiodes difficile (CD) infection confirmed by laboratory tests. A patient with a recurrent episode would be one with previous episodes.
    Units: Subjects
        Primary
    		 25 28 53
        Recurrent
    		 20 19 39
    Previous antibiotic
    The number of patients that received antibiotic treatment previous to receiving MBK-01/fidaxomicin.
    Units: Subjects
        Yes
    		 23 29 52
        No
    		 22 18 40

    End points

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    End points reporting groups
    Reporting group title
    MBK-01
    Reporting group description
    		 Patients randomized to MBK-01 received a single dose of 4 oral capsules of MBK-01.

    Reporting group title
    Fidaxomicin
    Reporting group description
    		 Patients randomized to fidaxomicin received treatment with oral fidaxomicin 200mg/12h for 10 days

    Subject analysis set title
    Patients with a primary episode of CDI assigned to MBK-01
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in MBK-01 group that presented a primary episode of CDI

    Subject analysis set title
    Patients with a primary episode of CDI assigned to fidaxomicin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in fidaxomicin group that presented a primary episode of CDI

    Subject analysis set title
    Patients with a recurrence of CDI assigned to MBK-01
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in MBK-01 group that presented a recurrent episode of CDI

    Subject analysis set title
    Patients with a recurrence of CDI assigned to fidaxomicin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in fidaxomicin group that presented a recurrent episode of CDI

    Subject analysis set title
    Patients with no previous antibiotic assigned to MBK-01
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in MBK-01 group that did not receive antibiotic pre-treatment before the treatment with MBK-01

    Subject analysis set title
    Patients with no previous antibiotic assigned to fidaxomicin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients in MBK-01 group that did not receive antibiotic pre-treatment before the treatment with fidaxomicin

    Subject analysis set title
    Baseline visit, MBK-01 group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the MBK-01 group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at the baseline visit (V1).

    Subject analysis set title
    Baseline visit, fidaxomicin group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the fidaxomicin group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at the baseline visit (V1).

    Subject analysis set title
    Visit 4, MBK-01 group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the MBK-01 group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at visit 4 (V4, 8 weeks).

    Subject analysis set title
    Visit 4, fidaxomicin group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the fidaxomicin group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at visit 4 (V4, 8 weeks).

    Subject analysis set title
    Visit 6, MBK-01 group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the MBK-01 group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at visit 6 (V6, 6 months).

    Subject analysis set title
    Visit 6, fidaxomicin group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients from the fidaxomicin group in whom the quality of life measured by the SF-36 questionnaire was reported and analysed at visit 6 (V6, 6 months).

    Primary: Absence of diarrhoea from Clostridioides difficile

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    End point title
    		 Absence of diarrhoea from Clostridioides difficile
    End point description
    Absence of recurrence (a new episode of Clostridioides difficile infection within 8 weeks after the onset of the previous episode).
    End point type
    Primary
    End point timeframe
    8 weeks after the onset of the previous episode of Clostridiodes difficile infection (8 weeks after the start of the treatment with MBK-01/fidaxomicin).
    End point values
    		 MBK-01 Fidaxomicin Patients with a primary episode of CDI assigned to MBK-01 Patients with a primary episode of CDI assigned to fidaxomicin Patients with a recurrence of CDI assigned to MBK-01 Patients with a recurrence of CDI assigned to fidaxomicin Patients with no previous antibiotic assigned to MBK-01 Patients with no previous antibiotic assigned to fidaxomicin
    Number of subjects analysed
    37
    40
    21
    27
    16
    13
    17
    15
    Units: patients
        Recurrence
    4
    9
    1
    1
    3
    8
    0
    3
        No recurrence
    33
    31
    20
    26
    13
    5
    17
    12
    Statistical analysis title
    		 Non-inferiority analysis of recurrence probability
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as a difference of proportions between MBK-01 (P1) and fidaxomicin group (P2). The proportions indicate the probability of no recurrence among the total patients in each group. There are 77 evaluable for recurrence (37 in MBK-01 group and 40 in Fidaxomicin group). Reasons for non-evaluable are: death, forbidden medication, investigator decision, adverse event, informed consent withdrawal and transfer to another hospital.
    Comparison groups
    Fidaxomicin v MBK-01
    Number of subjects included in analysis
    77
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.013 [2]
    Method
    		 Miettinen-Nurminen
    Parameter type
    		 Difference of proportions
    Point estimate
    2.228
    Confidence interval
         level
    		 97.06%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [1] - Non inferiority margin: -0.10. Null hypothesis: P1-P2 ≤-0.10 Alternative hypothesis: P1-P2 > -0.10 α=0.0221
    [2] - Confidence interval for the point estimate was not calculated. It is inputed as 0 and 100.
    Statistical analysis title
    		 Superiority analysis of recurrence probability
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as an Odds Ratio of the probability of no recurrence in each group, using the MBK-01 group as a reference. There are 77 evaluable for recurrence (37 in MBK-01 group and 40 in Fidaxomicin group). Reasons for non-evlauable are: death, forbidden medication, investigator decision, adverse event, informed consent withdrawal and transfer to another hospital.
    Comparison groups
    MBK-01 v Fidaxomicin
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.228
    Method
    		 Wald method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.395
    Confidence interval
         level
    		 97.79%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 10.624
    Notes
    [3] - α=0.0221
    Statistical analysis title
    		 Non-inferiority analysis of primary CDI subgroup
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as a difference of proportions between MBK-01 (P1) and fidaxomicin group (P2). The proportions indicate the probability of no recurrence among the total patients in each group. There are 48 evaluable for recurrence (21 in MBK-01 group and 27 in Fidaxomicin group). Reasons for non-evaluable are: adverse event, forbidden medication and death.
    Comparison groups
    Patients with a primary episode of CDI assigned to MBK-01 v Patients with a primary episode of CDI assigned to fidaxomicin
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority [4]
    P-value
    		 = 0.013 [5]
    Method
    		 Miettinen-Nurminen
    Parameter type
    		 Difference of proportions
    Point estimate
    2.228
    Confidence interval
         level
    		 97.06%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [4] - Non inferiority margin: -0.10. Null hypothesis: P1-P2 ≤-0.10 Alternative hypothesis: P1-P2 > -0.10 α=0.0294
    [5] - Confidence interval for the point estimate was not calculated. It is inputed as 0 and 100.
    Statistical analysis title
    		 Superiority analysis of primary CDI subgroup
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as an Odds Ratio of the probability of no recurrence in each group, using the MBK-01 group as a reference. There are 48 evaluable for recurrence (21 in MBK-01 group and 27 in Fidaxomicin group). Reasons for non-evaluable are: adverse event, forbidden medication and death.
    Comparison groups
    Patients with a primary episode of CDI assigned to MBK-01 v Patients with a primary episode of CDI assigned to fidaxomicin
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 1
    Method
    		 Wald method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.769
    Confidence interval
         level
    		 97.79%
         sides
    2-sided
         lower limit
    		 0.019
         upper limit
    		 31.82
    Notes
    [6] - α=0.0294
    Statistical analysis title
    		 Non-inferiority analysis of recurrent CDI subgroup
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as a difference of proportions between MBK01 (P1) and fidaxomicin group (P2). The proportions indicate the probability of no recurrence among the total patients in each group. There are 29 evaluable for recurrence (16 in MBK-01 group and 13 in Fidaxomicin group). Reasons for non-evaluable are: investigator decision, forbidden medication, transfer to another hospital, death and adverse event.
    Comparison groups
    Patients with a recurrence of CDI assigned to MBK-01 v Patients with a recurrence of CDI assigned to fidaxomicin
    Number of subjects included in analysis
    29
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority [7]
    P-value
    		 = 0.003 [8]
    Method
    		 Miettinen-Nurminen
    Parameter type
    		 Difference of proportions
    Point estimate
    2.744
    Confidence interval
         level
    		 97.06%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [7] - Non inferiority margin: -0.10. Null hypothesis: P1-P2 ≤-0.10 Alternative hypothesis: P1-P2 > -0.10 α=0.0294
    [8] - Confidence interval for the point estimate was not calculated. It is inputed as 0 and 100.
    Statistical analysis title
    		 Superiority analysis of recurrent CDI subgroup
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as an Odds Ratio of the probability of no recurrence in each group, using the MBK-01 group as a reference. There are 29 evaluable for recurrence (16 in MBK-01 group and 13 in Fidaxomicin group). Reasons for non-evaluable are: investigator decision, forbidden medication, transfer to another hospital, death and adverse event.
    Comparison groups
    Patients with a recurrence of CDI assigned to fidaxomicin v Patients with a recurrence of CDI assigned to MBK-01
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.027
    Method
    		 Wald method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.933
    Confidence interval
         level
    		 97.79%
         sides
    2-sided
         lower limit
    		 0.762
         upper limit
    		 63.12
    Notes
    [9] - α=0.0294
    Statistical analysis title
    		 Non-inferiority analysis of no pretreated subgroup
    Statistical analysis description
    The compared efficacy of the two treatments was assessed as a difference of proportions between MBK-01 (P1) and fidaxomicin group (P2). The proportions indicate the probability of no recurrence among the total patients in each group. There are 32 evaluable for recurrence (17 in MBK-01 group and 15 in Fidaxomicin group). Reasons for non-evaluable are: forbidden medication, adverse event, transfer to another hospital and investigator decision.
    Comparison groups
    Patients with no previous antibiotic assigned to MBK-01 v Patients with no previous antibiotic assigned to fidaxomicin
    Number of subjects included in analysis
    32
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority [10]
    P-value
    		 = 0.008 [11]
    Method
    		 Miettinen-Nurminen
    Parameter type
    		 Difference of proportion
    Point estimate
    2.396
    Confidence interval
         level
    		 97.06%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [10] - Non inferiority margin: -0.10. Null hypothesis: P1-P2 ≤-0.10 Alternative hypothesis: P1-P2 > -0.10 α=0.0294
    [11] - Confidence interval for the point estimate was not calculated. It is inputed as 0 and 100.

    Secondary: Favourable/unfavourable outcome

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    End point title
    		 Favourable/unfavourable outcome
    End point description
    An unfavourable outcome is defined as the detection within 48-72 hours from the start of treatment of a worsening of the episode of diarrhoea (defined as at least one stool more than at baseline, with baseline being considered as the time of initiation of study treatment) and, additionally, at least one of the following criteria: 1. Increase of the C-reactive protein (CRP) value (>5% of the value at baseline). 2. Increase of the absolute value of leukocytes (>5% of the value at baseline). 3. Progression to sepsis: hypotension or organ failure with no other apparent cause.
    End point type
    Secondary
    End point timeframe
    48-72 hours from the start of study treatment.
    End point values
    		 MBK-01 Fidaxomicin Patients with a primary episode of CDI assigned to MBK-01 Patients with a primary episode of CDI assigned to fidaxomicin Patients with a recurrence of CDI assigned to MBK-01 Patients with a recurrence of CDI assigned to fidaxomicin Patients with no previous antibiotic assigned to MBK-01 Patients with no previous antibiotic assigned to fidaxomicin
    Number of subjects analysed
    43
    45
    25
    27
    19
    18
    20
    17
    Units: patients
        Favourable
    43
    44
    25
    26
    19
    18
    20
    16
        Unfavourable
    0
    1
    0
    1
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Time to recurrence

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    End point title
    		 Time to recurrence
    End point description
    The baseline visit is taken as the start date. The end date will depend on whether the patient has had a recurrence at visit 4 (8 weeks after the start of study treatment): - If the patient has had a recurrence, the end date is the date on which the recurrence occurred. - If the patient has not had a recurrence, the end date is either the end of study date or the last available date. - If the patient has not had a recurrence and is ongoing, the last available date is imputed as the end date.
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of study treatment.
    End point values
    		 MBK-01 Fidaxomicin Patients with a primary episode of CDI assigned to MBK-01 Patients with a primary episode of CDI assigned to fidaxomicin Patients with a recurrence of CDI assigned to MBK-01 Patients with a recurrence of CDI assigned to fidaxomicin Patients with no previous antibiotic assigned to MBK-01 Patients with no previous antibiotic assigned to fidaxomicin
    Number of subjects analysed
    37
    40
    21
    27
    16
    13
    17
    15
    Units: weeks
        arithmetic mean (standard deviation)
    24.70 ( 1.34 )
    22.40 ( 1.53 )
    26.30 ( 1.268 )
    26.70 ( 0.872 )
    22.40 ( 2.240 )
    13.10 ( 3.01 )
    0 ( 0 )
    22.40 ( 2.31 )
    Statistical analysis title
    		 Time to recurrence analysis
    Comparison groups
    Fidaxomicin v MBK-01
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3 [12]
    Method
    		 Regression, Cox
    Parameter type
    		 Likelihood Ratio Test
    Point estimate
    1.29
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [12] - The Likelihood Ratio Test does not provide a confidence interval. It is inputed as 0 and 100.
    Statistical analysis title
    		 Time to recurrence of primary CDI subgroup
    Comparison groups
    Patients with a primary episode of CDI assigned to MBK-01 v Patients with a primary episode of CDI assigned to fidaxomicin
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8 [13]
    Method
    		 Regression, Cox
    Parameter type
    		 Likelihood Ratio Test
    Point estimate
    0.07
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [13] - The Likelihood Ratio Test does not provide a confidence interval. It is inputed as 0 and 100.
    Statistical analysis title
    		 Time to recurrence of recurrent CDI subgroup
    Comparison groups
    Patients with a recurrence of CDI assigned to MBK-01 v Patients with a recurrence of CDI assigned to fidaxomicin
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02 [14]
    Method
    		 Regression, Cox
    Parameter type
    		 Likelihood Ratio Test
    Point estimate
    5.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [14] - The Likelihood Ratio Test does not provide a confidence interval. It is inputed as 0 and 100.
    Statistical analysis title
    		 Time to recurrence of no pretreated subgroup
    Statistical analysis description
    Arithmetic mean and standard deviation of time to recurrence in MBK-01 group are inputed as 0 because there were no recurrences in this group.
    Comparison groups
    Patients with no previous antibiotic assigned to MBK-01 v Patients with no previous antibiotic assigned to fidaxomicin
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.04 [15]
    Method
    		 Regression, Cox
    Parameter type
    		 Likelihood Ratio Test
    Point estimate
    4.09
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [15] - The Likelihood Ratio Test does not provide a confidence interval. It is inputed as 0 and 100.

    Secondary: Overall survival: patients

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    End point title
    		 Overall survival: patients
    End point description
    Deaths indicated as number of events.
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of the treatment.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: patients
        Events
    1
    1
    No statistical analyses for this end point

    Secondary: Overall survival: time

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    End point title
    		 Overall survival: time
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of the treatment
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: weeks
        arithmetic mean (standard error)
    26.80 ( 0.712 )
    27 ( 0.581 )
    Statistical analysis title
    		 Overall survival analysis
    Comparison groups
    MBK-01 v Fidaxomicin
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9 [16]
    Method
    		 Regression, Cox
    Parameter type
    		 Likelihood Ratio Test
    Point estimate
    0.02
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [16] - The Likelihood Ratio Test does not provide a confidence interval. It is inputed as 0 and 100.

    Secondary: Quality of life

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    End point title
    		 Quality of life
    End point description
    Quality of life is measured by the Short Form-36 Health Survey (SF-36), which consists of 36 questions (items) that assess both positive and negative states of quality of life. These 36 items cover the following areas: physical function, physical role, bodily pain, general health, vitality, social role, emotional role and mental health. For each area, the scale ranges from 0 (the worst health status for that dimension) to 100 (the best health status).
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of study treatment. It was assesed at baseline visit (V1), visit 4 (V4, 8 weeks) and visit 6 (V6, 6 months).
    End point values
    		 Baseline visit, MBK-01 group Baseline visit, fidaxomicin group Visit 4, MBK-01 group Visit 4, fidaxomicin group Visit 6, MBK-01 group Visit 6, fidaxomicin group
    Number of subjects analysed
    42
    46
    30
    31
    12
    11
    Units: punctuation
    arithmetic mean (standard deviation)
        Physical function
    56.9 ( 35.9 )
    57.07 ( 33.71 )
    68.5 ( 30.6 )
    62.58 ( 30.44 )
    77.5 ( 27.01 )
    77.73 ( 27.14 )
        Bodily pain
    52.91 ( 29.84 )
    57.25 ( 29.07 )
    35.19 ( 29.19 )
    40.5 ( 28.33 )
    35.19 ( 33.78 )
    27.27 ( 28.27 )
        General health
    55.13 ( 17.07 )
    54.85 ( 20.62 )
    47.18 ( 18.04 )
    49.13 ( 17.5 )
    41.03 ( 15.5 )
    38.46 ( 16.14 )
        Vitality
    38.1 ( 11.52 )
    35.69 ( 18.56 )
    36.39 ( 17.02 )
    40.86 ( 11.85 )
    35.42 ( 7.22 )
    36.36 ( 8.56 )
        Social role
    65.08 ( 15.53 )
    63.77 ( 19.02 )
    63.33 ( 14.78 )
    63.44 ( 11.72 )
    59.72 ( 11.14 )
    69.7 ( 10.05 )
        Emotional role
    59.13 ( 39.04 )
    68.3 ( 32.18 )
    82.78 ( 25.7 )
    70.43 ( 28.04 )
    86.11 ( 22.29 )
    84.09 ( 20.57 )
        Mental health
    55.27 ( 16.92 )
    56.06 ( 17.17 )
    60 ( 16.42 )
    57.83 ( 13.84 )
    63.69 ( 11.97 )
    62.34 ( 12.81 )
        Physical role
    33.48 ( 33.44 )
    36.55 ( 32.81 )
    69.17 ( 35.84 )
    57.46 ( 30.64 )
    72.92 ( 29.95 )
    74.43 ( 34.51 )
    Statistical analysis title
    		 Analysis of the group and physical function
    Statistical analysis description
    The relationship between the treatment group and the changes in physical function was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.749
    Method
    		 ANOVA
    Confidence interval
    Notes
    [17] - α=0.0221. F (contrast statistic) = 0.104. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and physical function
    Statistical analysis description
    The relationship between the passing of time and the changes in physical function was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.62
    Method
    		 ANOVA
    Confidence interval
    Notes
    [18] - α=0.0221. F (contrast statistic) = 0.249. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and physical function
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in physical function was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.16
    Method
    		 ANOVA
    Confidence interval
    Notes
    [19] - α=0.0221. F (contrast statistic) = 2.024. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and bodily pain
    Statistical analysis description
    Therelationship between the treatment group and the changes in bodily pain was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.614
    Method
    		 ANOVA
    Confidence interval
    Notes
    [20] - α=0.0221. F (contrast statistic) = 0.257. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and bodily pain
    Statistical analysis description
    The relationship between the passing of time and the changes in bodily pain was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 0.007 [22]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [21] - α=0.0221. F (contrast statistic) = 7.705. Degrees of freedom: 1, 56
    [22] - Effect size = 0.046
    Statistical analysis title
    		 Analysis of group-time and bodily pain
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in bodily pain was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.718
    Method
    		 ANOVA
    Confidence interval
    Notes
    [23] - α=0.0221. F (contrast statistic) = 0.132. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and general health
    Statistical analysis description
    The relationship between the treatment group and the changes in general health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 = 0.494
    Method
    		 ANOVA
    Confidence interval
    Notes
    [24] - α=0.0221. F (contrast statistic) = 0.474. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and general health
    Statistical analysis description
    The relationship between the passing of time and the changes in general health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    P-value
    		 = 0.339
    Method
    		 ANOVA
    Confidence interval
    Notes
    [25] - α=0.0221. F (contrast statistic) = 0.932. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and general health
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in general health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    P-value
    		 = 0.38
    Method
    		 ANOVA
    Confidence interval
    Notes
    [26] - α=0.0221. F (contrast statistic) = 0.783. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and vitality
    Statistical analysis description
    The relationship between the treatment group and the changes in vitality was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 0.79
    Method
    		 ANOVA
    Confidence interval
    Notes
    [27] - α=0.0221. F (contrast statistic) = 0.072. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and vitality
    Statistical analysis description
    The relationship between the passing of time and the changes in vitality was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 = 0.498
    Method
    		 ANOVA
    Confidence interval
    Notes
    [28] - α=0.0221. F (contrast statistic) = 0.465. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and vitality
    Statistical analysis description
    The effect of the interaction between the treatment group and the passing of time in the changes in vitality was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 = 0.023
    Method
    		 ANOVA
    Confidence interval
    Notes
    [29] - α=0.0221. F (contrast statistic) = 5.490. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and social role
    Statistical analysis description
    The relationship between the treatment group and the changes in social role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.553
    Method
    		 ANOVA
    Confidence interval
    Notes
    [30] - α=0.0221. F (contrast statistic) = 0.356. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and social role
    Statistical analysis description
    The relationship between the passing of time and the changes in social role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.718
    Method
    		 ANOVA
    Confidence interval
    Notes
    [31] - α=0.0221. F (contrast statistic) = 0.132. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and social role
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in social role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.574
    Method
    		 ANOVA
    Confidence interval
    Notes
    [32] - α=0.0221. F (contrast statistic) = 0.319. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and emotional role
    Statistical analysis description
    The relationship between the treatment group and the changes in emotional role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    P-value
    		 = 0.49
    Method
    		 ANOVA
    Confidence interval
    Notes
    [33] - α=0.0221. F (contrast statistic) = 0.482. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time in emotional role
    Statistical analysis description
    The relationship between the passing of time and the changes in emotional role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    P-value
    		 = 0.032
    Method
    		 ANOVA
    Confidence interval
    Notes
    [34] - α=0.0221. F (contrast statistic) = 4.850. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and emotional role
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in emotional role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    P-value
    		 = 0.145
    Method
    		 ANOVA
    Confidence interval
    Notes
    [35] - α=0.0221. F (contrast statistic) = 2.181. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and mental health
    Statistical analysis description
    The relationship between the treatment group and the changes in mental health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    P-value
    		 = 0.467
    Method
    		 ANOVA
    Confidence interval
    Notes
    [36] - α=0.0221. F (contrast statistic) = 0.535. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and mental health
    Statistical analysis description
    The relationship between the passing of time and the changes in mental health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    P-value
    		 = 0.1
    Method
    		 ANOVA
    Confidence interval
    Notes
    [37] - α=0.0221. F (contrast statistic) = 2.795. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of group-time and mental health
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in mental health was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    P-value
    		 = 0.89
    Method
    		 ANOVA
    Confidence interval
    Notes
    [38] - α=0.0221. F (contrast statistic) = 0.019. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the group and physical role
    Statistical analysis description
    The relationship between the treatment group and the changes in physical role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [39]
    P-value
    		 = 0.742
    Method
    		 ANOVA
    Confidence interval
    Notes
    [39] - α=0.0221. F (contrast statistic) = 0.109. Degrees of freedom: 1, 56
    Statistical analysis title
    		 Analysis of the time and physical role
    Statistical analysis description
    The relationship between the passing of time and the changes in physical role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    P-value
    		 < 0.001 [41]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [40] - α=0.0221. F (contrast statistic) = 21.912. Degrees of freedom: 1, 56
    [41] - Effect size = 0.109
    Statistical analysis title
    		 Analysis of group-time and physical role
    Statistical analysis description
    The relationship between the interaction treatment group-passing of time and the changes in physical role was analysed with ANOVA. The total number of subjects in this analysis (172) is calculated as the addition of the number of patients in all the visits, and does not reflect the actual number of patients analysed.
    Comparison groups
    Baseline visit, MBK-01 group v Baseline visit, fidaxomicin group v Visit 4, MBK-01 group v Visit 4, fidaxomicin group v Visit 6, MBK-01 group v Visit 6, fidaxomicin group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [42]
    P-value
    		 = 0.089
    Method
    		 ANOVA
    Confidence interval
    Notes
    [42] - α=0.0221. F (contrast statistic) = 2.986. Degrees of freedom: 1, 56

    Secondary: Number of Adverse Events

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    End point title
    		 Number of Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study for up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse events
    89
    103
    No statistical analyses for this end point

    Secondary: Number of patients who have had Adverse Events

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    End point title
    		 Number of patients who have had Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study for up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse events
    36
    38
    No statistical analyses for this end point

    Secondary: Number of Serious Adverse Events

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    End point title
    		 Number of Serious Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Serious adverse events were assessed continuously during the study for up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Serious Adverse Events
    11
    5
    No statistical analyses for this end point

    Secondary: Number of patients who have had Serious Adverse Events

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    End point title
    		 Number of patients who have had Serious Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Serious adverse events were assessed continuously during the study for up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Serious Adverse Events
    9
    4
    No statistical analyses for this end point

    Secondary: Number of treatment-related Adverse Events

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    End point title
    		 Number of treatment-related Adverse Events
    End point description
    Adverse events classified under the categories "Likely" and "Definitely related" are considered treatment-related Adverse Events.
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study for up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse Events
        Unrelated
    93
    79
        Unlikely
    2
    2
        Possible
    5
    7
        Likely
    3
    1
        Definitely related
    0
    0
    Statistical analysis title
    		 Analysis of relation to treatment
    Statistical analysis description
    Relationship between the treatment groups and the Adverse Events related to treatment is analysed. Adverse events classified under the categories "Likely" and "Definitely related" are considered treatment-related Adverse Events.
    Comparison groups
    Fidaxomicin v MBK-01
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.692 [43]
    Method
    		 Chi-squared corrected
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.459
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [43] - The assumption according to which no more than 25% of the cells in the table should have an expected frequency is violated. Yates' continuity correction is reported. Confidence interval was not calculated. It is inputed as 0 and 100.

    Secondary: Severity of Adverse Events

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    End point title
    		 Severity of Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study for up to 6 monthsafter treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse Events
        Mild
    77
    70
        Moderate
    22
    17
        Severe
    4
    1
        Life threatening
    0
    0
        Death
    0
    1
    Statistical analysis title
    		 Analysis of severity
    Statistical analysis description
    Relationship between the treatment groups and the severity of the Adverse Events is analysed.
    Comparison groups
    MBK-01 v Fidaxomicin
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.429 [44]
    Method
    		 Chi-squared corrected
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.768
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 100
    Notes
    [44] - The assumption according to which no more than 25% of the cells in the table should have an expected frequency is violated. Yates' continuity correction is reported. Confidence interval was not calculated. It is inpupted as 0 and 100.

    Secondary: Adverse Events in relation to Clostridium difficile infection

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    End point title
    		 Adverse Events in relation to Clostridium difficile infection
    End point description
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study por up to 6 months after treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse Events
        Diarrhoea
    17
    28
        Clostridium diffcile colitis
    0
    1
        Clostridium difficile infection
    3
    4
        Positive Clostridium test
    1
    0
        Total
    21
    33
    No statistical analyses for this end point

    Secondary: Mortality associated with CDI

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    End point title
    		 Mortality associated with CDI
    End point description
    The number of deaths related to Clostridium difficile infection is assessed.
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of the treatment.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: patients
    0
    0
    No statistical analyses for this end point

    Secondary: ICU admissions

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    End point title
    		 ICU admissions
    End point description
    The number of Intensive Care Unit Admissions related to Clostridium difficile infection or to the treatment was assessed.
    End point type
    Secondary
    End point timeframe
    Up to 6 months after the start of the treatment.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: patients
        Related to CDI
    0
    0
        Related to the treatment
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Adverse Events of Special Interest

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    End point title
    		 Number of Adverse Events of Special Interest
    End point description
    AESI (Adverse Events of Special Interest) have also been considered either AEs or SAEs. AESI defined by protocol and Statistical Analysis Plan (SAP) are as follows: abdominal cramping, bloating and pain; flatulence, nausea, vomiting, transient fever (>38ºC), increased C-reactive protein (>20 mg/L), fatigue, weight gain, headache, anorexia, constipation, diarrhea, ulcerative colitis, bacteremia, inflammatory bowel disease and enteropathogenic infections. Some events that, in the clinician’s opinion should be considered AESI despite not being isted as such in the list provided in the protocol and the SAP, are included in this analysis. In addition, some events were not considered AESI by the clinician despite being listed as such in the protocol and the SAP, hence they were not included in this analysis.
    End point type
    Secondary
    End point timeframe
    Adverse events were assessed continuously during the study for up to 6 months afer treatment, until the end-of-study visit.
    End point values
    		 MBK-01 Fidaxomicin
    Number of subjects analysed
    45
    47
    Units: Adverse events
    64
    63
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Regarding safety assessments, adverse events were assessed continuously during the study for up for 6 months after treatment until the end-of-study visit (End of Study date: 15 Nov 2023).
    Adverse event reporting additional description
    For the adverse events, System Organ Class (SOC) and Preferred Term (PT) were reported.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    MBK-01
    Reporting group description
    		 Patients randomized to MBK-01 received a single dose of 4 oral capsules of MBK-01.

    Reporting group title
    Fidaxomicin
    Reporting group description
    		 Patients randomized to fidaxomicin received treatment with oral fidaxomicin 200mg/12h for 10 days.

    Serious adverse events
    		 MBK-01 Fidaxomicin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 45 (20.00%)
    4 / 47 (8.51%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    1
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal cancer
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammatory bowel disease
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal fluid collection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2.13%
    Non-serious adverse events
    		 MBK-01 Fidaxomicin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    36 / 45 (80.00%)
    38 / 47 (80.85%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Hypertensive crisis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Prophylaxis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Tooth extraction
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Medical device site reaction
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 47 (2.13%)
         occurrences all number
    3
    1
    Polyp
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 47 (4.26%)
         occurrences all number
    3
    2
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Catarrh
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Mixed anxiety and depressive disorder
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    11 / 45 (24.44%)
    6 / 47 (12.77%)
         occurrences all number
    13
    7
    Cardiac murmur
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Clostridium test positive
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 47 (4.26%)
         occurrences all number
    0
    2
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Spinal fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Synovial rupture
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    3 / 45 (6.67%)
    4 / 47 (8.51%)
         occurrences all number
    3
    4
    Migraine
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Leukocytosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2
    Abdominal pain
         subjects affected / exposed
    4 / 45 (8.89%)
    3 / 47 (6.38%)
         occurrences all number
    4
    3
    Abdominal pain lower
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Colitis ulcerative
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2
    Dental discomfort
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    16 / 45 (35.56%)
    22 / 47 (46.81%)
         occurrences all number
    17
    27
    Erosive duodenitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Flatulence
         subjects affected / exposed
    2 / 45 (4.44%)
    4 / 47 (8.51%)
         occurrences all number
    2
    4
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Haemorroids
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 47 (2.13%)
         occurrences all number
    2
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 47 (4.26%)
         occurrences all number
    3
    3
    Odynophagia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Reflux gastritis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 47 (2.13%)
         occurrences all number
    4
    2
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Hidradenitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Toxic skin eruption
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Vascular purpura
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Microalbuminuria
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Oliguria
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Infections and infestations
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    COVID-19
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Clostridium difficile infection
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 47 (6.38%)
         occurrences all number
    2
    3
    Cystitis
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 47 (0.00%)
         occurrences all number
    3
    0
    Influenza
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Perineal abscess
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 47 (4.26%)
         occurrences all number
    3
    2
    Metabolism and nutrition disorders
    Folate deficiency
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Aug 2021
    Changes in the exclusion criteria were made, which directly impact on the recruitment capacity of the study. The modification of the exclusion criteria was motivated by the following causes: 1. The modification or elimination of some of the initially proposed exclusion criteria significantly favours the recruitment capacity of the centres involved in the study. 2. The proposed modifications of the exclusion criteria do not affect the fulfilment of the objectives (primary and secondary) of the study. The increase in the study's recruitment capacity favours the fulfilment of the study's objectives within the established timeframe. 3. The population of patients treated in the clinical trial is more heterogeneous than the previous one, and therefore more representative of the population intended to be treated with MBK-01.
    15 Dec 2021
    Four new sites were added to the clinical trial.
    07 Feb 2022
    Changes in the inclusion and exclusion criteria were made, by allowing the use of antibiotic pre-treatment for patients included in the study, making necessary to consider a washout period prior to the administration of the study treatment. The modification of the inclusion and exclusion criteria was motivated by the following reasons: 1. Due to the low recruitment rate and the fact that the modification of inclusion and exclusion criteria directly impacts on recruitment capacity, the aim is to improve the recruitment capacity of the sites involved. 2. The proposed modifications do not affect the fulfilment of the objetives of the study. Increased recruitment capactiy woul help meet the objectives within the stablished timeframe. 3. The population to be treated in the study is more representative of the population intended to be treated with MBK-01. In addition, the time for carrying out the intermediate analysis of the study was modified, so that it would be performed when half of the patients had completed treatment. In this way, the partial efficacy results of the study would be known earlier.
    12 May 2022
    Two new sites were added to the clinical trial.
    16 Sep 2022
    The clinical trial population was broadened and the study inclusion criteria were modified, motivated by the following reasons: 1. Due to the low recruitment rate and the fact that the modification of inclusion criteria directly impacts on recruitment capacity, the aim is to improve the recruitment capacity of the sites involved. 2. The proposed modifications do not affect the fulfilment of the objetives of the study. An increased recruitment capacitiy woul help meet the objectives within the stablished timeframe. 3. The adjustments that were made allow an additional group of patients with Clostridioides difficile infection to have access to a potentially effective treatment, while still using the same patient population as before and without compromising the data already collected in the study. 4. The extension of the deadline for detection of Clostridioides difficile toxin within the 7 days prior to enrolment of the patient in the trial was made to take into account the duration of vancomycin treatment and the washout period that may be required by some participants. The statistical analysis was adapted to include the assessment of an additional secondary safety variable, which would provide more information on the safety of the investigational medicinal product. The sample size was adapted without affecting the achievement of the study objectives. Some aspects of the study design were modified, allowing the inclusion in the trial of patients previously treated with fidaxomicin if the duration of treatment was not therapeutic. In addition, it was included that the interim analysis of the study could lead to early discontinuation of the study, with the aim of early termination of the study, in order to maintain the safety of the participants.
    21 Jul 2023
    The measures taken in October 2022 were included in the protocol, following the recommendations of the guidance document ‘Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Additional Safety Protections Pertaining to Monkeypox Virus’, issued by the FDA in 2022, and which were notified to the AEMPS by Urgent Safety Notification on 21/10/2022. The donor inclusion criteria were modified in line with these measures. The sample size was adapted from 66 to 82 patients, in order to adjust the expected number of patients recruited to the actual observed drop-out rate of the study, without affecting the achievement of the study objectives. A new planned study schedule was established, taking into account the changes in the number of patients to be recruited.
    09 Oct 2023
    The definition of the study variables were revised to add the odds ratio and logistic regression in the analysis of the main efficacy variable, thus allowing the study of the probability of recurrence in addition to the number of episodes of diarrhea. The variable "Duration of hospitalisation" was deleted as many patients were treated as outpatients or the reason of admission was not CDI. The variable "Duration of the treatment" was also deleted. Complementary ITT subpopulations were added for the analysis of probability of recurrence and time to recurrence. The analysis of covariates was eliminated. In addition, a revision of the definition of recurrence of CDI was added. The reformulation of the primary variable resulted in the revision of the statiscal calculation of the sample size, which would be based on a confidence level of 97.06%, Odds Ratio of 2.5, stastical power of 80% and loss rate of 50%, generating a sample size of 104 subjects. The dropout rate was maintained at 50%. Criteria were defined to allow the early termination of the clinical trial. The possibility of early termination could provide advantages such as minimisation of risks to subjects, greater efficiency in the management of research resources, and/or, where appropriate, acceleration of product development and market access. The possibility of early termination of the trial makes it necessary to plan for a second, intermediate statistical analysis to assess trends in efficacy and safety outcomes. The high rate of loss to follow-up, as well as the possibility of premature trial termination, made it necessary to define a strategy for the follow-up of patients withdrawn before completing the scheduled follow-up. Thus, it was defined that all patients withdrawn before the end of the planned follow-up should have an end-of-study visit ≥ 30 days after initiation of treatment, in which, as a minimum, relevant safety information should be collected.

    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.
    The statistical power of the study was limited due to the small sample size, which may have prevented finding statistically significant differences between MBK-01 and fidaxomicin in some analyses.
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