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    Clinical Trial Results:
    Double-blind, randomized, placebo-controlled, phase II dose-finding study comparing different doses of ZED1227 capsules with placebo in the treatment of non-alcoholic fatty liver disease (NAFLD) with significant fibrosis

    Summary
    EudraCT number
    		 2021-002253-29
    Trial protocol
    		 ES   PL   DE   BE  
    Global end of trial date
    05 Jul 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Aug 2024
    First version publication date
    09 Aug 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CEC-011/NAS
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05305599
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Dr. Falk Pharma GmbH
    Sponsor organisation address
    Leinenweberstraße 5, Freiburg im Breisgau, Germany, 79108
    Public contact
    Dept. of Clinical Research&Developm, Dr. Falk Pharma GmbH, +49 49761 1514 0, zentrale@drfalkpharma.de
    Scientific contact
    Dept. of Clinical Research&Developm, Dr. Falk Pharma GmbH, +49 0761 1514 0, zentrale@drfalkpharma.de
    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
    29 Aug 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jul 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this trial is to evaluate the efficacy of three doses of ZED1227 versus (vs.) placebo for the 12-week treatment of patients with NAFLD with significant fibrosis
    Protection of trial subjects
    Close supervision of subjects by implementing interim visits every 4 weeks during treatment and one follow up vist at weeks after end of treatment to guarantee their safety and wellbeing. Prior to recruitment of patients, all relevant documents of the clinical study were submitted and approved by the Independent Ethics Committees (IECs) responsible for the participating investigators. Written consent documents embodied the elements of informed consent as described in the Declaration of Helsinki, the ICH Guidelines for Good Clinical Practice (GCP) and were in accordance with all applicable laws and regulations. The informed consent form and patient information sheet described the planned and permitted uses, transfers and disclosures of the patient's personal data and personal health information for purposes of conducting the study. The informed consent form and the patient information sheet further explained the nature of the study, its objectives and potential risks and benefits as well as the date informed consent was given. Before being enrolled in the clinical trial, every patient was informed that participation in this trial was voluntary and that he/she could withdraw from the study at any time without giving a reason and without having to fear any loss in his/her medical care. The patient’s consent was obtained in writing before the start of the study. By signing the informed consent, the patient declared that he/she was participating voluntarily and intended to follow the study protocol instructions and the instructions of the investigator and to answer the questions asked during the course of the trial.
    Background therapy
    		 None
    Evidence for comparator
    		 As there is no standard therapy, placebo was used as comparator
    Actual start date of recruitment
    05 Apr 2022
    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
    Poland: 58
    Country: Number of subjects enrolled
    Spain: 38
    Country: Number of subjects enrolled
    Belgium: 16
    Country: Number of subjects enrolled
    France: 49
    Country: Number of subjects enrolled
    Germany: 25
    Worldwide total number of subjects
    186
    EEA total number of subjects
    186
    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)
    117
    From 65 to 84 years
    69
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 In total 186 patients were included in 5 countries (Germany, Poland, Spain, France and Belgium) from April 2022 to July 2023.

    Pre-assignment
    Screening details
    		 Screening criteria: Signed informed consent • male or female, 18 and 75 years of age • Diagnosed with NAFLD and significant fibroses (stages 2 or 3). 334 patients were screened. Thereof 186 patients were randomised. Of those 177 received study medication and were included in the safety analysis set (SAF). 174 were included in FAS.

    Pre-assignment period milestones
    Number of subjects started
    		 186
    Number of subjects completed
    		 174

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Adverse event, non-fatal: 1
    Reason: Number of subjects
    		 Randomized by mistake: 1
    Reason: Number of subjects
    		 Consent withdrawn by subject: 7
    Reason: Number of subjects
    		 Other: 2
    Reason: Number of subjects
    		 Missing: 1
    Period 1
    Period 1 title
    Overall trial (treatment phase) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Blinding was achieved by the application of the same number of capsule s(ZED1227 or placebo) to each patient. Placebo capsules matched verum capsules in size, taste, and appearance.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group A
    Arm description
    		 ZED1227 (low dose) 10 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZED1227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule twice a day: 1 capsule in the morning and 1 capsule in the evening

    Arm title
    		 Group B
    Arm description
    		 ZED1227 (middle dose) 25 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZED1227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule twice a day: 1 capsule in the morning and 1 capsule in the evening

    Arm title
    		 Group C
    Arm description
    		 ZED1227 (high dose) 50 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZED1227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule twice a day: 1 capsule in the morning and 1 capsule in the evening

    Arm title
    		 Group D
    Arm description
    		 Placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule twice a day: 1 capsule in the morning and 1 capsule in the evening

    Number of subjects in period 1 [1]
    		Group A Group B Group C Group D
    Started
    41
    43
    45
    45
    Completed
    40
    42
    43
    43
    Not completed
    1
    1
    2
    2
         Lack of Compliance
    -
    1
    -
    -
         Physician decision
    -
    -
    1
    -
         Consent withdrawn by subject
    -
    -
    1
    1
         Adverse event, non-fatal
    1
    -
    -
    1
    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: To meet the requirements of the system, the number of patients entered in the trial period refects the FAS population. These are the patients, that were randomized, received study medication and at least one ample for analysis of the primary endpoint was available.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial (treatment phase)
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial (treatment phase) Total
    Number of subjects
    		 174 174
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 111 111
        From 65-75 years
    		 63 63
    Age continuous
    Units: years
        median (full range (min-max))
    		 63.0 (18 to 74) -
    Gender categorical
    Units: Subjects
        Female
    		 78 78
        Male
    		 96 96
    Subject analysis sets

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized patients who received at least one dose of the IMP and had baseline serum levels of PRO-C3 collected.

    Subject analysis sets values
    		 FAS
    Number of subjects
    174
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    111
        From 65-75 years
    63
    Age continuous
    Units: years
        median (full range (min-max))
    63 (18 to 74)
    Gender categorical
    Units: Subjects
        Female
    78
        Male
    96

    End points

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    End points reporting groups
    Reporting group title
    Group A
    Reporting group description
    		 ZED1227 (low dose) 10 mg

    Reporting group title
    Group B
    Reporting group description
    		 ZED1227 (middle dose) 25 mg

    Reporting group title
    Group C
    Reporting group description
    		 ZED1227 (high dose) 50 mg

    Reporting group title
    Group D
    Reporting group description
    		 Placebo

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized patients who received at least one dose of the IMP and had baseline serum levels of PRO-C3 collected.

    Primary: Primary endpoint: relative change in PRO-C3

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    End point title
    		 Primary endpoint: relative change in PRO-C3
    End point description
    The relative change (%) of serum levels of released N-terminal propeptide of type III collagen (PRO-C3)
    End point type
    Primary
    End point timeframe
    Between baseline and the end-of-treatment (EOT)/withdrawal visit
    End point values
    		 Group A Group B Group C Group D
    Number of subjects analysed
    41
    43
    45
    45
    Units: Change of PRO-C3
        least squares mean (standard error)
    0.3 ( 3.56 )
    10.2 ( 3.46 )
    -1.2 ( 3.48 )
    6.8 ( 3.37 )
    Statistical analysis title
    		 Primary efficacy endpoint FAS
    Comparison groups
    Group A v Group D
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0921
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.12
         upper limit
    		 3.1
    Statistical analysis title
    		 Primary efficacy endpoint FAS
    Comparison groups
    Group B v Group D
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5863
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.16
         upper limit
    		 12.92
    Statistical analysis title
    		 Primary efficacy endpoint FAS
    Comparison groups
    Group C v Group D
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0479
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.57
         upper limit
    		 1.43

    Secondary: Secondary Endpoint: relative change of ELF Score

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    End point title
    		 Secondary Endpoint: relative change of ELF Score
    End point description
    End point type
    Secondary
    End point timeframe
    Between baseline and the end-of-treatment (EOT)/withdrawal visit
    End point values
    		 Group A Group B Group C Group D FAS
    Number of subjects analysed
    40
    43
    45
    45
    0 [1]
    Units: %
        arithmetic mean (standard deviation)
    0.70 ( 6.023 )
    1.68 ( 5.431 )
    -0.98 ( 5.562 )
    0.26 ( 5.514 )
    ( )
    Notes
    [1] - No determined for whole population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events were assessed from BL visit, at interim visits (week 4 and week 8), at the end of treatment visit week 12 and at the Follow up visit week 16 .
    Adverse event reporting additional description
    Treatment-Emergent and Post-Treatment Adverse Events
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Group A
    Reporting group description
    		 ZED1227 (low dose) 10 mg

    Reporting group title
    Group B
    Reporting group description
    		 ZED1227 (middle dose) 25 mg

    Reporting group title
    Group C
    Reporting group description
    		 ZED1227 (high dose) 50 mg

    Reporting group title
    Group D
    Reporting group description
    		 Placebo

    Serious adverse events
    		 Group A Group B Group C Group D
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 42 (4.76%)
    3 / 45 (6.67%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Cardiac disorders
    Dilated cardiomyopathy
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Hemorrhoidal hemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anorectal varices
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal hemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Sleep apnea syndrome
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Group A Group B Group C Group D
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 42 (73.81%)
    26 / 45 (57.78%)
    27 / 45 (60.00%)
    33 / 45 (73.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Fibroma
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Monoclonal gammopathy
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypertension
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    0
    1
    Surgical and medical procedures
    Hyperhidrosis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin burning sensation
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    2
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Malaise
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Swelling face
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Reproductive system and breast disorders
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    2
    Epistaxis
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Asthma
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Catarrh
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Depression
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Irritability
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    2
    Lipase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood insulin increased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Glutamate dehydrogenase increased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    High density lipoprotein decreased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Prothrombin time shortened
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Smear cervix
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Transaminases increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Arthropod bite
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Face injury
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hand fracture
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Congenital, familial and genetic disorders
    Hydrolcele
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Atrial Fibrllation
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dilated cardiomyopathy
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 42 (7.14%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
         occurrences all number
    3
    1
    1
    1
    Paraesthesia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    0
    1
    Sciatica
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    0
    1
    Disturbance in attention
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Migraine
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Restless leg
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    0
    0
    2
    Anaemia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vertigo positional
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye disorders
    Astigmatism
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Blepharitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cataract
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Eye inflammation
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Ocular hypertension
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Photophobia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    5 / 42 (11.90%)
    2 / 45 (4.44%)
    3 / 45 (6.67%)
    6 / 45 (13.33%)
         occurrences all number
    5
    2
    3
    6
    Constipation
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    2
    1
    0
    2
    Flatulence
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    3 / 45 (6.67%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    3
    1
    Abdominal distension
         subjects affected / exposed
    1 / 42 (2.38%)
    3 / 45 (6.67%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Nausea
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    1
    0
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    2
    Abdominal pain lower
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    1
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    Anorectal varices
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Breath odour
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Chronic gastritis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Defaecation urgency
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Dry mouth
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Duodenogastr
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Eructation
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Faeces discoloured
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oesophageal ulcer
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pancreatitis chronic
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Proctalgia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rectal tenesmus
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Regurgitation
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tongue discomfort
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 42 (7.14%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
         occurrences all number
    3
    2
    1
    1
    Rash
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    2
    1
    0
    1
    Acne
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Alopecia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Psoriasis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash pruritic
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Skin irritation
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Renal colic
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    2
    2
    Osteoarthritis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Bursitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Synovial cyst
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Torticollis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    5 / 42 (11.90%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    2 / 45 (4.44%)
         occurrences all number
    5
    1
    2
    2
    Nasopharyngitis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    5 / 45 (11.11%)
         occurrences all number
    1
    1
    3
    6
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
         occurrences all number
    1
    1
    1
    3
    Bronchitis
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
         occurrences all number
    3
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    3
    2
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    2
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    1
    0
    2
    Pneumonia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    1
    0
    2
    Influenza
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    2
    Conjunctivitis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Abscess limb
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infected bite
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lyme disease
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Periodontitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Diabetes
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Folate deficiency
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gout
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jan 2023
    One global amendment dated 11 Jan 2023 was made to the original protocol, dated 11 Oct 2021

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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