Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A multicentre, prospective, randomized, double-blind, parallel-group placebo-controlled clinical study for the assessment of the immunomodulatory efficacy, safety and clinical impact after three and six months treatment with a sublingual polyvalent bacterial vaccine (in oral mucosa) in women with recurrent urinary tract infections (rUTIs).

    Summary
    EudraCT number
    		 2013-001838-17
    Trial protocol
    		 ES   GB  
    Global end of trial date
    04 Nov 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Oct 2022
    First version publication date
    11 Oct 2022
    Other versions
    Summary report(s)
    		 Synopsis MV140-SLG-003

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MV140-SLG-003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02543827
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 UROMUNE: MV140
    Sponsors
    Sponsor organisation name
    INMUNOTEK
    Sponsor organisation address
    PUNTO MOBI, 5, ALCALA DE HENARES, Spain, 28805
    Public contact
    Miguel Casanovas, INMUNOTEK S.L., +34 691490175, mcasanovas@inmunotek.com
    Scientific contact
    Miguel Casanovas, INMUNOTEK S.L., +34 691490175, mcasanovas@inmunotek.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Jan 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to determine if immunization with the bacterial vaccine MV140 would reduce the risk of and/or prevent urinary tract infections (UTI) compared to placebo in women with recurrent UTIs.
    Protection of trial subjects
    All subjects received the first dose at the hospital in order to teach them the proper administration of the drug, and to observe the patient's first in touch with the immunotherapy. All adverse events that occured during the course of the study were recorded and assessed. These were thoroughly explored, both during a scheduled control and controls at any time when a subject reported an abnormal occurrence. Protection of Personal Data and guarantee of digital rights. Regulation (Eu) 2016/679 of the European Parliament and of The Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation). To ensure the rights of the subjects, the Main Researcher or collaborating researchers, through the information sheet, the objectives and requirements of the Study, the nature of the study drug and its possible side effects, will be explained to the subject in understandable language for the Subject. The information to be provided includes: a description of the endpoints of the study, the methodology used, the type of treatment, the benefits that the subject may obtain from the treatment as well as the risks they may have and the right to withdraw from study if desired.
    Background therapy
    		 Currently, antibiotics remain the main strategy for the treatment of UTIs. However, there is high incidence of adverse reactions associated with the use of antibiotics. Moreover, multi-resistance of the bacteria to antibiotics is widely increasing, leading that more than 40% of the bacterial strains are resistant to available antibiotics in some regions of the world. Altogether, it is reasonable to consider other preventive strategies than antibiotics such as those that reinforce the natural mechanisms of pathogen defense, such as immunostimulation or vaccination. A number of studies have shown that the oral administration of bacterial immune stimulants ameliorates RUTIs in adults and children by reducing the number, duration and severity of infectious clinical episodes. Thus, these clinical studies using a bacterial extract, which contains immunostimulatory components extracted from 18 uropathogenic Escherichia coli strains, have been shown to reduce the incidence of recurrent infections of the lower urinary tract in both children and adults. The sublingual route for administration of bacterial preparations is very safe and effective for stimulating, in a strong and long-lasting way, the antigen-specific mucosa and the systemic humoral and cellular immunity. Stimulation of the oral mucosa may produce effects in distant mucosa, by activating effector mechanisms of innate and acquired immunity through the mucosal associated lymphoid tissue (MALT). The oral cavity (inductive site) contains a high density of antigen-presenting cells, mainly the Langerhans cells, with a high stimulating activity. These cells subsequently migrate to the lymph nodes, where they interact with T and B lymphocytes to induce their differentiation to effector cells. After their activation, the lymphocytes re-circulate through the different compartments of the mucosa-associated lymphoid tissue (MALT), and access different mucous membranes, including the genitourinary tract (effector site). T
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Sep 2015
    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: 200
    Country: Number of subjects enrolled
    United Kingdom: 40
    Worldwide total number of subjects
    240
    EEA total number of subjects
    200
    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)
    186
    From 65 to 84 years
    54
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The time of recruitment was between October 2015 (first patient enrolled) and April 2018 (last patient enrolled).

    Pre-assignment
    Screening details
    		 This study included subjects (female) with rUTI, classified as non-complicated UTIs. The number os subjects screened were 240. The number of subjects who received treatment (excluded screening failures) were 230. Efficacy evaluable population (Intention-to-treat) were 215 and those who finished were 195.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    Neither the investigator nor the subject knew about the treatment provided. The members of the investigator team, the monitoring team and the people responsible for analysing the data did not have access to blinded data either. The Researcher/Pharmacist had a way to break the code due to an emergency. The code break would only have been carried out in emergencies, in the case the researcher needed to know in order to provide appropriate medical treatment or to ensure the safety of the subjects

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group I active treatment for 6 months
    Arm description
    		 Sublingual MV140 treatment at a dose of 300 FTU/mL. Subjects in Group I received active treatment consisting of a bacterial vaccine sublingually for 6 months (i.e. MV140 6M).
    Arm type
    		 Experimental

    Investigational medicinal product name
    UROMUNE
    Investigational medicinal product code
    MV140
    Other name
    Pharmaceutical forms
    Sublingual spray
    Routes of administration
    Sublingual use
    Dosage and administration details
    Sublingual MV140 treatment at a dose of 300 FTU/mL, administered to 80 subjects with recurrent urinary tract infections, daily for 6 months. The active trial medication was a polyvalent bacterial vaccine; the pharmaceutical form was a glycerinated suspension containing a mixture of four inactivated non-lysated bacterial concentrates (V121 Escherichia coli 25%, V113 Klebsiella pneumoniae 25%, V125 Enterococcus faecalis 25%, V127 Proteus vulgaris 25%) as active substance, at a final concentration of 300 Formazin Turbidity Units (FTU)/mL (equivalent to 10^9 bacteria/mL). As excipients, it contains 0.63 g of glycerol, pineapple artificial flavouring (0.01 mL), sodium chloride (9 mg/mL) and water (q.s. for 1 mL). The trial medication was administered through the sublingual route, applying two sprays daily.

    Arm title
    		 Group II placebo for 6 months
    Arm description
    		 Subjects in Group II received placebo sublingually for 6 months
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Sublingual spray
    Routes of administration
    Sublingual use
    Dosage and administration details
    It contained an identical solution to the test product but no active substance (without the inactivated non-lysate bacterial concentrates), and was administrated through the sublingual route, applying two sprays daily. The composition was glycerol 0.63 g, pineapple artificial flavouring 0.01 mL, sodium chloride 9 mg/mL and water q.s. for 1 mL.

    Arm title
    		 Group III active treatment 3 months + 3 months of placebo
    Arm description
    		 Subjects in Group III received 3 months of active treatment and then 3 months of placebo sublingually (i.e. MV140 3M).
    Arm type
    		 Experimental

    Investigational medicinal product name
    UROMUNE+ Placebo
    Investigational medicinal product code
    MV140
    Other name
    Uromune+Placebo
    Pharmaceutical forms
    Sublingual spray
    Routes of administration
    Sublingual use
    Dosage and administration details
    Active treatment (MV140) daily for 3 months, followed by 3 months of placebo. The active trial medication was a polyvalent bacterial vaccine; the pharmaceutical form was a glycerinated suspension containing a mixture of four inactivated non-lysated bacterial concentrates (V121 Escherichia coli 25%, V113 Klebsiella pneumoniae 25%, V125 Enterococcus faecalis 25%, V127 Proteus vulgaris 25%) as active substance, at a final concentration of 300 Formazin Turbidity Units (FTU)/mL (equivalent to 10^9 bacteria/mL). As excipients, it contains 0.63 g of glycerol, pineapple artificial flavouring (0.01 mL), sodium chloride (9 mg/mL) and water (q.s. for 1 mL). The trial medication was administered through the sublingual route, applying two sprays daily.

    Number of subjects in period 1 [1]
    		Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo
    Started
    75
    78
    77
    Completed
    61
    65
    67
    Not completed
    14
    13
    10
         Screening failure
    4
    1
    -
         Consent withdrawn by subject
    6
    5
    2
         Adverse event, non-fatal
    2
    1
    3
         Pregnancy
    -
    3
    2
         Other reasons
    -
    -
    1
         Lost to follow-up
    2
    2
    -
         Adverse reaction
    -
    1
    2
    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: The number of subjects in the baseline period are considered to be 230, the ones that were finally enrolled in the trial. The worldwide number of subjects enrolled were 240, without screening failures.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Group I active treatment for 6 months
    Reporting group description
    		 Sublingual MV140 treatment at a dose of 300 FTU/mL. Subjects in Group I received active treatment consisting of a bacterial vaccine sublingually for 6 months (i.e. MV140 6M).

    Reporting group title
    Group II placebo for 6 months
    Reporting group description
    		 Subjects in Group II received placebo sublingually for 6 months

    Reporting group title
    Group III active treatment 3 months + 3 months of placebo
    Reporting group description
    		 Subjects in Group III received 3 months of active treatment and then 3 months of placebo sublingually (i.e. MV140 3M).

    Reporting group values
    		 Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo Total
    Number of subjects
    		 75 78 77 230
    Age categorical
    Individuals aged 18-75 years were enrolled. The median age was 48.0 [interquartile range, IQR, 34.0-61.5], 54.5 [IQR, 38.0-66.0] and 47.0 [34.0-58.0] years for groups receiving placebo and MV140 for 3 or 6 months.
    Units: Subjects
        Adults (18-64 years)
    		 63 60 49 172
        From 65-84 years
    		 12 18 28 58
    Gender categorical
    Women with recurrent urinary infections (rUTIs)
    Units: Subjects
        Female
    		 75 78 77 230
    Subject analysis sets

    Subject analysis set title
    Efficacy Per-protocol population analysis
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Evaluable per-protocol population included randomized subjects who completed the efficacy period of 12 months and adequately complied with the protocol

    Subject analysis set title
    Efficacy Intention-to-treat population analysis
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The evaluable intention-to-treat population included all randomized subjects who completed week 12 according to the treatment assignment at randomisation.

    Subject analysis sets values
    		 Efficacy Per-protocol population analysis Efficacy Intention-to-treat population analysis
    Number of subjects
    193
    215
    Age categorical
    Individuals aged 18-75 years were enrolled. The median age was 48.0 [interquartile range, IQR, 34.0-61.5], 54.5 [IQR, 38.0-66.0] and 47.0 [34.0-58.0] years for groups receiving placebo and MV140 for 3 or 6 months.
    Units: Subjects
        Adults (18-64 years)
    145
    164
        From 65-84 years
    48
    51
    Age continuous
    Units: years
        median (full range (min-max))
    Gender categorical
    Women with recurrent urinary infections (rUTIs)
    Units: Subjects
        Female
    193
    215

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group I active treatment for 6 months
    Reporting group description
    		 Sublingual MV140 treatment at a dose of 300 FTU/mL. Subjects in Group I received active treatment consisting of a bacterial vaccine sublingually for 6 months (i.e. MV140 6M).

    Reporting group title
    Group II placebo for 6 months
    Reporting group description
    		 Subjects in Group II received placebo sublingually for 6 months

    Reporting group title
    Group III active treatment 3 months + 3 months of placebo
    Reporting group description
    		 Subjects in Group III received 3 months of active treatment and then 3 months of placebo sublingually (i.e. MV140 3M).

    Subject analysis set title
    Efficacy Per-protocol population analysis
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Evaluable per-protocol population included randomized subjects who completed the efficacy period of 12 months and adequately complied with the protocol

    Subject analysis set title
    Efficacy Intention-to-treat population analysis
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The evaluable intention-to-treat population included all randomized subjects who completed week 12 according to the treatment assignment at randomisation.

    Primary: Comparison of the number of episodes of UTIs in the 3 study groups in the 9 months study period following 3 months of intervention (placebo or immunization)

    		 Close Top of page
    End point title
    		 Comparison of the number of episodes of UTIs in the 3 study groups in the 9 months study period following 3 months of intervention (placebo or immunization)
    End point description
    Primary efficacy analysis will be based on the comparison of the average number of episodes of UTIs in the three study groups in the 9 months study period following 3 months of intervention (placebo or immunization).
    End point type
    Primary
    End point timeframe
    9 months
    End point values
    		 Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo
    Number of subjects analysed
    69
    76
    70
    Units: episodes
    median (inter-quartile range (Q1-Q3))
        UTI episodes
    0 (0.0 to 1.0)
    3 (0.5 to 6.0)
    0 (0.0 to 1.0)
    Statistical analysis title
    		 Median number of UTI episodes
    Statistical analysis description
    According to the normal distribution analyzed, UTI episodes were analyzed by chi-square and Kruskal-Wallis nonparametric tests, respectively, comparing the two treatment groups to the placebo group. Post hoc tests with Bonferroni adjustments were subsequently conducted to evaluate pairwise differences.
    Comparison groups
    Group I active treatment for 6 months v Group II placebo for 6 months v Group III active treatment 3 months + 3 months of placebo
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Kruskal-wallis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Secondary: Comparison of the proportion of subjects who remain infection free (no UTIs) in the three study groups in the 9-month study period following 3 months of intervention (placebo or immunization)

    		 Close Top of page
    End point title
    		 Comparison of the proportion of subjects who remain infection free (no UTIs) in the three study groups in the 9-month study period following 3 months of intervention (placebo or immunization)
    End point description
    End point type
    Secondary
    End point timeframe
    9 months study period following 3 months of intervention (placebo or immunization)
    End point values
    		 Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo
    Number of subjects analysed
    69
    76
    70
    Units: subjects
    number (not applicable)
        UTI-free participants
    40
    19
    46
    Statistical analysis title
    		 Proportion of UTI-free subjects
    Statistical analysis description
    According to the normal distribution analyzed, UTI episodes and UTI-free rates were analyzed by chi-square and Kruskal-Wallis nonparametric tests, respectively, comparing the two treatment groups to the placebo group. Post hoc tests with Bonferroni adjustments were subsequently conducted to evaluate pairwise differences.
    Comparison groups
    Group I active treatment for 6 months v Group II placebo for 6 months v Group III active treatment 3 months + 3 months of placebo
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Kruskal-wallis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    12 months
    Adverse event reporting additional description
    Safety was evaluated throughout the study by recording all adverse events and all adverse reactions.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Group I active treatment for 6 months
    Reporting group description
    		 Sublingual MV140 treatment at a dose of 300 FTU/mL. Subjects in Group I received active treatment consisting of a bacterial vaccine sublingually for 6 months.

    Reporting group title
    Group II placebo for 6 months
    Reporting group description
    		 Subjects in Group II received placebo sublingually for 6 months

    Reporting group title
    Group III active treatment 3 months + 3 months of placebo
    Reporting group description
    		 Subjects in Group III received 3 months of active treatment and then 3 months of placebo sublingually (i.e. MV140 3M).

    Serious adverse events
    		 Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    4 / 77 (5.19%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Surgical and medical procedures
    Oesophagogastric fundoplasty
    Additional description: Surgery for reflux
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric operation
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytodistension
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric bleeding
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Hysterectomy
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Kidney infection
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Group I active treatment for 6 months Group II placebo for 6 months Group III active treatment 3 months + 3 months of placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 75 (37.33%)
    39 / 78 (50.00%)
    34 / 77 (44.16%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leiomyoma
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Lipoma
    Additional description: Lipoma on the left arm
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Vascular disorders
    Haematoma
    Additional description: Haematoma on the left arm
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Metabolic surgery
    Additional description: Bariatric surgery
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Cholecystectomy
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Foot operation
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Parathyroid gland operation
    Additional description: Parathyroid adenoma surgery
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Skin neoplasm excision
    Additional description: Removed carcinoma of the left cheek
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    3 / 78 (3.85%)
    0 / 77 (0.00%)
         occurrences all number
    1
    3
    0
    Pyrexia
    Additional description: 1 sobject affected by Febrile syndrome and 1 subject affected by Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    Malaise
    Additional description: General malaise
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    2 / 77 (2.60%)
         occurrences all number
    0
    1
    2
    Swelling
    Additional description: Neck lump
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Oedema peripheral
    Additional description: Oedema in the lower limbs
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    Peripheral swelling
    Additional description: Group II: 1 subject affected by swollen foot Group III: 1 subject affected by swollen legs
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    0
    1
    1
    Pain
    Additional description: Unknown pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Immune system disorders
    Hypersensitivity
    Additional description: Allergic reaction to antibiotic
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    1
    1
    1
    Food allergy
    Additional description: Food allergic reaction
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Reproductive system and breast disorders
    Atrophic vulvovaginitis
    Additional description: Atrophic vagina
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Aphonia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Cough
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Dyspnoea
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Lung disorder
    Additional description: Pulmonary disease
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Increased viscosity of upper respiratory secretion
    Additional description: Thick mucus
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Depression
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    0
    1
    1
    Stress
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Depression suicidal
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Drug abuse
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Barium swallow
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Colonoscopy
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Endoscopy
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Weight increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Fibula fracture
    Additional description: Broken fibula
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    1
    Contusion
    Additional description: Contusion in right hip
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Road traffic accident
    Additional description: Traffic accident whiplash syndrome
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Injury
    Additional description: Trauma from a fall
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    Atrial fibrillation
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Palpitations
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Dizziness
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    3 / 77 (3.90%)
         occurrences all number
    0
    0
    3
    Facial paralysis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    Migraine
    Additional description: Migraine headaches
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    Hypoaesthesia
    Additional description: Numbness in neck
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Syncope
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 78 (2.56%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    Neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    Tympanic membrane perforation
    Additional description: Perforated eardrum
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Vertigo
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    Eye disorders
    Eye pruritus
    Additional description: Itchy eyes
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    2
    2
    1
    Constipation
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    0
    1
    1
    Diverticulum
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Dysphagia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Abdominal discomfort
    Additional description: Gastric discomfort
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Gastrooesophageal reflux disease
    Additional description: Group I: 1 subject affected by Gastroesophageal reflux (1 occurrence) Group III: 1 subject affected by Worsening of Gastro-oesophageal reflux/GOR (1 occurrence)
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    1
    Enterocolitis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Haemorrhoids
    Additional description: Internal hemorrhoids
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal pain
    Additional description: Intestinal spasm
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia oral
    Additional description: Oral paresthesia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Oral pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Toothache
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    2 / 77 (2.60%)
         occurrences all number
    0
    0
    3
    Hepatobiliary disorders
    Biliary colic
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Blister
    Additional description: Group III: - 1 subject affected by blister on ears - 1 subject affected by blister on shoulders
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    2 / 77 (2.60%)
         occurrences all number
    0
    0
    2
    Acne
    Additional description: Chin spots
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus
    Additional description: Itchy mouth and Generalized itching. Group I: 0 subjects affected Group II: 2 subjects affected by itchy mouth (2 occurrences) Group III: 2 subjects affected by itchy mouth (4 occurrences) and 1 by generalized itching (1 occurrence).
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 78 (2.56%)
    3 / 77 (3.90%)
         occurrences all number
    0
    2
    5
    Lichen sclerosus
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Skin reaction
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Urticaria
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Hypertonic bladder
    Additional description: Overactive bladder
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Renal colic
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    3
    0
    Trigonitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Endocrine disorders
    Adrenal mass
    Additional description: Left kidney nodule
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Thyroid disorder
    Additional description: Thyroid
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    1
    Intervertebral disc protrusion
    Additional description: Cervical hernia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Flank pain
    Additional description: Flank pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Arthralgia
    Additional description: Gonalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Osteoporosis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
    Additional description: Pain in lower limbs
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Mobility decreased
    Additional description: Reduced mobility
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal pain
    Additional description: Right shoulder pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    Infections and infestations
    Candida infection
    Additional description: Candidiasis
         subjects affected / exposed
    1 / 75 (1.33%)
    3 / 78 (3.85%)
    4 / 77 (5.19%)
         occurrences all number
    1
    4
    7
    Vaginal infection
    Additional description: Vaginitis
         subjects affected / exposed
    2 / 75 (2.67%)
    4 / 78 (5.13%)
    3 / 77 (3.90%)
         occurrences all number
    2
    5
    4
    Lower respiratory tract infection
    Additional description: Chest infection
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 78 (3.85%)
    2 / 77 (2.60%)
         occurrences all number
    3
    7
    3
    Appendicitis
    Additional description: Acute appendicitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    0
    1
    2
    Tooth abscess
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth infection
    Additional description: Dental root canal infection
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Gastroenteritis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Gingivitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    Papilloma viral infection
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Postoperative wound infection
    Additional description: Infection surgery points
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Oral infection
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    3
    1
    1
    Ear infection
    Additional description: Otitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    1
    Pharyngitis
    Additional description: Group I: 1 subject affected by throat infection (1 occurrence) The rest of subjects were affected by pharyngitis
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 78 (3.85%)
    2 / 77 (2.60%)
         occurrences all number
    2
    3
    2
    Pneumonia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Pyelonephritis
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 75 (4.00%)
    1 / 78 (1.28%)
    1 / 77 (1.30%)
         occurrences all number
    3
    3
    1
    Sinusitis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 78 (2.56%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    Tonsillitis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 78 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    1
    Urethritis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Viral rash
    Additional description: Viral exanthem
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 78 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngeal abscess
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Groin pain
    Additional description: Suprainguinal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 78 (1.28%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jan 2014
    Three centres were included to complete subject recruitment established in the protocol. The centres would refer subjects to the University Hospital of Salamanca.
    01 Oct 2014
    Modification of the study design based on consultation to the Spanish Agency of Medicines and Medical Devices: -Inclusion of a Stage II (12 additional months of follow-up) and associated modifications -Addition of inclusion and exclusion criteria
    01 Dec 2015
    Incorporating changes resulting from including Royal Berkshire Hospital, Reading UK in the study.
    01 Mar 2016
    Incorporating changes resulting from the application to MHRA.
    01 Aug 2018
    Cancellation of Stage II (12 additional months of follow-up) due to loss of follow-up and high dropout rate
    02 Dec 2019
    -Inclusion of Bioclever S.L. for support in the statistical content of the study. -Protocol modification and rewording in the following sections, based on their review: • Objectives • Efficacy outcomes and evaluation • Statistics

    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.

    European Medicines Agency © 1995-Mon Apr 29 06:15:04 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA