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    Clinical Trial Results:
    Flucloxacillin as an inducer of CYP-enzymes

    Summary
    EudraCT number
    		 2020-004044-28
    Trial protocol
    		 DK  
    Global end of trial date
    28 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions
    Summary report(s)
    		 Annotation for missing values

    Trial information

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    Trial identification
    Sponsor protocol code
    AKF-396
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04840641
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Southern Denmark
    Sponsor organisation address
    J.B.Winsløws Vej 19, Odense, Denmark, 5000
    Public contact
    Clinical Pharmacology and Pharmacy, Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark , dbiversen@health.sdu.dk
    Scientific contact
    Clinical Pharmacology and Pharmacy, Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark , dbiversen@health.sdu.dk
    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
    11 Oct 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Dec 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of this study is to investigate if treatment with flucloxacillin increases drug metabolism in healthy volunteers through induction of cytochrome P450 (CYP) enzymes, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. This study was a randomized, self-controlled cross-over study. 12 healthy volunteers completed the study according to the protocol. Due to technical difficulties we were not able to calculate the changes of CYP2C19
    Protection of trial subjects
    We measured blood pressure for the trial subjects to monitor the health of trial subjects after intake of the Basel Cocktail. Trial subjects were asked about adverse events during the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Mar 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
    Denmark: 14
    Worldwide total number of subjects
    14
    EEA total number of subjects
    14
    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)
    14
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 We recruited healthy men and women from March 2021 until June 2021. All trial subjects consented to participate in the trial. If in- and exclusion criteria were fulfilled trial subjects were randomized to start in phase A or phase B. Based on In- and exclusion criteria a medical doctor decided if trial subjects could participate in the trial

    Pre-assignment
    Screening details
    		 Trial subjects were screened based on in and exclusion criteria. A medical doctor decided if trial subjects full-filled the criteria and could enter the trial.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Baseline
    Arm description
    		 We measured the baseline level of CYP enzymes without intake of flucloxacillin. All trial subjects worked as their own control and entered all periods. 5 people started in the Baseline period before entering the treatment period, and 7 people started in the treatment period before entering the Baseline period.
    Arm type
    		 No administration of drugs

    Investigational medicinal product name
    No drugs
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    No drugs were administered as the baseline level of CYP enzymes were measured in this arm

    Number of subjects in period 1 [1]
    		Baseline
    Started
    12
    Completed
    12
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: We included 14 healthy subjects. 2 subjects withdrew from the study, one due to adverse events and one due to personal reasons. We only based the analysis on 12 subjects as they all completed the study according to the protocol.
    Period 2
    Period 2 title
    Flucloxacillin
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Flucloxacillin treatement
    Arm description
    		 Trial subjects ingested flucloxacillin for 31 days. We measured induction of CYP-enzymes at 10 days and 28 days. All trial subjects worked as their own control and entered all periods. 5 people started in the Baseline period before entering the treatment period, and 7 people started in the treatment period before entering the Baseline period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Flucloxacillin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    During the trial, trial subjects ingested 1 gram flucloxacillin 3 times daily.

    Number of subjects in period 2
    		Flucloxacillin treatement
    Started
    12
    Completed
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Baseline
    Reporting group description
    		 -

    Reporting group values
    		 Baseline Total
    Number of subjects
    		 12 12
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 12 12
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 23 (22 to 24) -
    Gender categorical
    Units: Subjects
        Female
    		 4 4
        Male
    		 8 8

    End points

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    End points reporting groups
    Reporting group title
    Baseline
    Reporting group description
    		 We measured the baseline level of CYP enzymes without intake of flucloxacillin. All trial subjects worked as their own control and entered all periods. 5 people started in the Baseline period before entering the treatment period, and 7 people started in the treatment period before entering the Baseline period.
    Reporting group title
    Flucloxacillin treatement
    Reporting group description
    		 Trial subjects ingested flucloxacillin for 31 days. We measured induction of CYP-enzymes at 10 days and 28 days. All trial subjects worked as their own control and entered all periods. 5 people started in the Baseline period before entering the treatment period, and 7 people started in the treatment period before entering the Baseline period.

    Primary: change in AUC of midazolam after 28 days of treatment

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    End point title
    		 change in AUC of midazolam after 28 days of treatment
    End point description
    Midazolam AUC after 28 days of flucloxacillin treatment
    End point type
    Primary
    End point timeframe
    At baseline and 28 days of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12 [1]
    12 [2]
    Units: ng h ml^-1
    geometric mean (confidence interval 95%)
        Midazolam
    0.7 (0.53 to 0.92)
    0.73 (0.61 to 0.88)
    Notes
    [1] - Reporting group 1 is the change in AUC between baseline and 10 days of flucloxacillin
    [2] - Reporting group 2 is the change in AUC between baseline and 28 days of flucloxacillin
    Statistical analysis title
    		 Geometric mean ratio
    Statistical analysis description
    We only included trial subjects who finished the whole study according to the protocol. Based on this we excluded 2 trial subjects
    Comparison groups
    Flucloxacillin treatement v Baseline
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [3]
    Method
    		 No p-value
    Parameter type
    		 Geometric mean ratio
    Confidence interval
    Notes
    [3] - We did not calculate p-values, but instead, the confidence interval 95%. If the geometric mean ration contained 1, it was not considered statistically significant.

    Secondary: Change in AUC of the six substrates midazolam (substrate of CYP3A4), caffeine (CYP1A2), efavirenz (CYP2B6), losartan (CYP2C9), omeprazole (CYP2C19) and metoprolol (CYP2D6) and their main metabolites after 10 and 28 days

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    End point title
    		 Change in AUC of the six substrates midazolam (substrate of CYP3A4), caffeine (CYP1A2), efavirenz (CYP2B6), losartan (CYP2C9), omeprazole (CYP2C19) and metoprolol (CYP2D6) and their main metabolites after 10 and 28 days
    End point description
    End point type
    Secondary
    End point timeframe
    Comparing 10 and 28 days of flucloxacillin treatment with baseline measurements
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: ng*h ml^-1
    median (inter-quartile range (Q1-Q3))
        Caffeine
    0.79 (0.74 to 0.84)
    0.75 (0.63 to 0.89)
        Efairenz
    1.0 (0.91 to 1.1)
    1.18 (1.1 to 1.3)
        Losartan
    0.9 (0.76 to 1.1)
    0.82 (0.67 to 1.0)
        Metoprolol
    0.8 (0.47 to 1.4)
    0.62 (0.41 to 0.93)
        Midazolam
    0.7 (0.53 to 0.92)
    0.73 (0.61 to 0.88)
        1-OH-midazolam
    0.85 (0.71 to 1.0)
    0.89 (0.75 to 1.0)
        E3174
    0.89 (0.84 to 0.93)
    0.81 (0.71 to 0.92)
        OH-metoprolol
    0.87 (0.45 to 1.7)
    0.64 (0.19 to 2.1)
        Paraxanthine
    0.81 (0.73 to 0.9)
    0.78 (0.69 to 0.88)
        8-OH-efavirenz
    0.69 (0.59 to 0.8)
    0.84 (0.74 to 0.95)
        Omeprazole
    0.87 (0.67 to 1.1)
    0.82 (0.57 to 1.1)
        5-OH-omeprazole
    0.84 (0.72 to 0.97)
    0.78 (0.67 to 0.91)
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [4]
    Method
    		 No p-value
    Confidence interval
    Notes
    [4] - We did not calculate the p-value. Instead, we calculated the 95 % CI. if CI 95% for GMR contained 1, it was not considered statistically signifikant.

    Secondary: Change in Cmax of the Basel Cocktail and their main metabolites

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    End point title
    		 Change in Cmax of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    Comparing data from baseline until day 10 and 28 of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: ng*ml^-1
    geometric mean (confidence interval 95%)
        Midazolam
    0.92 (0.68 to 1.2)
    1.0 (0.84 to 1.2)
        Losartan
    0.98 (0.74 to 1.3)
    0.88 (0.61 to 1.3)
        Metoprolol
    0.8 (0.47 to 1.4)
    0.7 (0.56 to 0.86)
        Caffeine
    0.91 (0.84 to 0.99)
    0.97 (0.89 to 1.1)
        Efavirenz
    1.1 (0.94 to 1.3)
    1.35 (1.1 to 1.7)
        1-OH-midazolam
    1.0 (0.82 to 1.2)
    1.1 (0.89 to 1.3)
        E3174
    0.97 (0.85 to 1.1)
    0.93 (0.8 to 1.1)
        OH-metoprolol
    1.1 (0.77 to 1.7)
    0.93 (0.55 to 1.6)
        Paraxanthine
    1.0 (0.94 to 1.1)
    1.0 (0.9 to 1.1)
        8-OH-efavirenz
    0.78 (0.61 to 1.0)
    0.82 (0.67 to 1.0)
        Omeprazole
    0.91 (0.68 to 1.2)
    0.8 (0.66 to 1.2)
        5-OH-omeprazole
    0.9 (0.75 to 1.1)
    0.86 (0.66 to 1.1)
    Statistical analysis title
    		 Geometric mean ratio
    Statistical analysis description
    There were 12 subjects in this analysis as the study was self-controlled
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [5]
    Method
    		 Not provided
    Confidence interval
    Notes
    [5] - We did not calculate the p-value. instead we calculated the 95% confidence interval. If the geometric mean ratio CI 95% contained 1 it was not considered statistical signific

    Secondary: Change in T1/2 of the Basel Cocktail and their main metabolites

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    End point title
    		 Change in T1/2 of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    Measuring baseline and comparing to 10 and 28 days of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: T1/2 (hours)
    geometric mean (confidence interval 95%)
        Midazolam
    0.73 (0.6 to 0.9)
    0.58 (0.43 to 0.79)
        losartan
    1.0 (0.86 to 1.2)
    0.9 (0.79 to 1.0)
        metoprolol
    0.98 (0.64 to 1.5)
    1.2 (0.56 to 2.4)
        caffeine
    0.82 (0.8 to 0.85)
    0.79 (0.7 to 0.9)
        efavirenz
    1.01 (0.59 to 1.7)
    1.2 (0.95 to 1.4)
        1-OH-midazolam
    0.63 (0.28 to 1.4)
    0.54 (0.24 to 1.2)
        E3174
    0.99 (0.75 to 1.3)
    0.83 (0.68 to 1.0)
        OH-metoprolol
    1.3 (0.09 to 18.0)
    0.97 (0.05 to 17.2)
        paraxanthine
    0.87 (0.77 to 0.97)
    0.83 (0.73 to 0.93)
        8-OH-efavirenz
    1.0 (0.73 to 1.4)
    1.1 (0.81 to 1.6)
        Omeprazole
    1 (0.88 to 1.2)
    0.85 (0.69 to 1.1)
        5-OH-omeprazole
    0.89 (0.77 to 1)
    0.84 (0.67 to 1.1)
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [6]
    Method
    		 No p-value
    Parameter type
    		 GMR
    Confidence interval
    Notes
    [6] - We did not calculate the p-value. Instead, we calculated the 95 % CI. if CI 95% for GMR contained 1, it was not considered statistically signifikant.

    Secondary: change in AUCratio of the Basel Cocktail and their main metabolites

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    End point title
    		 change in AUCratio of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline measurements compared to 10 and 28 days of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: ratio
    geometric mean (confidence interval 95%)
        midazolam
    1.2 (0.93 to 1.5)
    1.3 (1.0 to 1.5)
        losartan
    0.98 (0.83 to 1.2)
    0.98 (0.82 to 1.2)
        metoprolol
    1.0 (0.52 to 2.0)
    0.90 (0.25 to 3.3)
        caffeine
    1.0 (0.96 to 1.1)
    1.0 (0.93 to 1.2)
        efavirenz
    0.69 (0.57 to 0.83)
    0.71 (0.63 to 0.80)
        Omeprazole
    0.97 (0.8 to 1.2)
    0.95 (0.7 to 1.3)
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [7]
    Method
    		 No p-value
    Confidence interval
    Notes
    [7] - We did not calculate the p-value. Instead, we calculated the 95 % CI. if CI 95% for GMR contained 1, it was not considered statistically signifikant.

    Secondary: change in metabolic ratio of the Basel Cocktail and their main metabolites

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    End point title
    		 change in metabolic ratio of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline measurements compared to 10 and 28 days of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: ratio
    geometric mean (confidence interval 95%)
        midazolam
    1.3 (1.1 to 1.6)
    1.4 (1.2 to 1.6)
        losartan
    1.1 (0.92 to 1.4)
    1.1 (0.78 to 1.7)
        metoprolol
    0.91 (0.57 to 1.5)
    0.96 (0.4 to 2.3)
        caffeine
    1.1 (1.1 to 1.2)
    1.3 (1.0 to 1.6)
        efavirenz
    0.65 (0.51 to 0.84)
    0.61 (0.51 to 0.73)
        Omeprazole
    0.98 (0.58 to 1.7)
    1.14 (0.63 to 2.1)
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [8]
    Method
    		 No p-value
    Parameter type
    		 Geometric mean ratio
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [8] - We calculated the 95% confidence interval instead of p-values.

    Secondary: change in formation clearance of the Basel Cocktail and their main metabolites

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    End point title
    		 change in formation clearance of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    At baseline and after 10 and 28 days of flucloxacillin treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12 [9]
    12 [10]
    Units: ml*h^-1*1000
    geometric mean (confidence interval 95%)
        Midazolam
    1.2 (0.76 to 1.8)
    1.7 (1.1 to 2.6)
        Losartan
    0.93 (0.71 to 1.2)
    0.91 (0.6 to 1.4)
        Metoprolol
    1.4 (0.87 to 2.1)
    2.0 (1.3 to 2.9)
        Caffeine
    1.4 (1.0 to 1.9)
    1.3 (1 to 1.6)
        Efavirenz
    0.78 (0.63 to 0.96)
    0.77 (0.64 to 0.93)
    Notes
    [9] - Reporting group 1 is the change in AUC between baseline and 10 days of flucloxacillin
    [10] - Reporting group 2 is the change in AUC between baseline and 28 days of flucloxacillin
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Flucloxacillin treatement v Baseline
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [11]
    Method
    		 No p-value was calculated
    Parameter type
    		 GMR
    Confidence interval
    Notes
    [11] - We did not calculate the p-value. Instead, we calculated the 95 % CI. if CI 95% for GMR contained 1, it was not considered statistically signifikant.

    Secondary: change in renal clearance of the Basel Cocktail and their main metabolites

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    End point title
    		 change in renal clearance of the Basel Cocktail and their main metabolites
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline compared to 10 and 28 days of treatment
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12 [12]
    12 [13]
    Units: ml*h^-1*1000
    geometric mean (confidence interval 95%)
        Midazolam
    0.89 (0.53 to 1.5)
    1.5 (0.83 to 2.6)
        Losartan
    0.78 (0.49 to 1.3)
    0.76 (0.45 to 1.3)
        Metoprolol
    0.88 (0.6 to 1.3)
    1.2 (0.87 to 1.5)
        Caffeine
    1.1 (0.61 to 1.7)
    1.2 (0.66 to 2.2)
        Efavirenz
    1 (0.75 to 1.5)
    0.88 (0.6 to 1.3)
    Notes
    [12] - Reporting group 2 is the change in AUC between baseline and 28 days of flucloxacillin
    [13] - Reporting group 2 is the change in AUC between baseline and 28 days of flucloxacillin
    Statistical analysis title
    		 Geometric mean ratio
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.05 [14]
    Method
    		 No p-value was calculated
    Parameter type
    		 GMR
    Confidence interval
    Notes
    [14] - We did not calculate the p-value. Instead, we calculated the 95 % CI. if CI 95% for GMR contained 1, it was not considered statistically signifikant.

    Secondary: Change in Ae (amount in urine) of the Basel Cocktail and their main metabolite

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    End point title
    		 Change in Ae (amount in urine) of the Basel Cocktail and their main metabolite
    End point description
    End point type
    Secondary
    End point timeframe
    After 10 and 28 days of flucloxacillin treatment compared to baseline. Values are geometric mean values.
    End point values
    		 Baseline Flucloxacillin treatement
    Number of subjects analysed
    12
    12
    Units: mg
    geometric mean (confidence interval 95%)
        Midazolam
    0.63 (0.41 to 0.97)
    1.1 (0.55 to 2.03)
        Losartan
    0.7 (0.45 to 1.1)
    0.62 (0.37 to 1.1)
        Metorprolol
    0.77 (0.57 to 1)
    0.7 (0.54 to 0.94)
        Caffeine
    0.89 (0.61 to 1.3)
    0.95 (0.52 to 1.7)
        Efavirenz
    1 (0.74 to 1.5)
    1 (0.73 to 1.5)
        1-OH-midazolam
    0.82 (0.68 to 1)
    0.82 (0.59 to 1.1)
        E3174
    0.83 (0.72 to 0.96)
    0.62 (0.56 to 0.99)
        OH-metoprolol
    1.2 (0.87 to 1.7)
    1.2 (0.89 to 1.7)
        Paraxanthine
    1.1 (0.8 to 1.5)
    1 (0.84 to 1.2)
        8-OH-efavirenz
    0.78 (0.66 to 0.91)
    0.91 (0.75 to 1.1)
    Statistical analysis title
    		 Geometric mean ratio
    Statistical analysis description
    There were 12 subjects in this analysis as the study was self-controlled
    Comparison groups
    Baseline v Flucloxacillin treatement
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 ≥ 0.05 [15]
    Method
    		 No p-value
    Parameter type
    		 GMR
    Confidence interval
    Notes
    [15] - We did not calculate the p-value. instead we calculated the 95% confidence interval. If the geometric mean ratio CI 95% contained 1 it was not considered statistical significant

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were were reported from intake of medicine in the trial and 2 weeks after the last dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 None
    Dictionary version
    0
    Reporting groups
    Reporting group title
    Ingesting flucloxacillin
    Reporting group description
    		 Adverse events for trial subjects ingesting flucloxacillin for 31 days

    Serious adverse events
    		 Ingesting flucloxacillin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 14 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ingesting flucloxacillin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 14 (78.57%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 14 (21.43%)
         occurrences all number
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 14 (7.14%)
         occurrences all number
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 14 (42.86%)
         occurrences all number
    6
    Nausea
         subjects affected / exposed
    5 / 14 (35.71%)
         occurrences all number
    5
    Constipation
         subjects affected / exposed
    1 / 14 (7.14%)
         occurrences all number
    1
    heartburn
         subjects affected / exposed
    1 / 14 (7.14%)
         occurrences all number
    1
    Infections and infestations
    Vaginal yeast infection
         subjects affected / exposed
    2 / 14 (14.29%)
         occurrences all number
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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