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   44393   clinical trials with a EudraCT protocol, of which   7405   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:
    Opened phase II controlled and randomized clinical trial to evaluate the efficacy in the intra-arterial infusion with mononuclear autologous bone marrow stem cells in patients with ischemic stroke

    Summary
    EudraCT number
    		 2013-002135-15
    Trial protocol
    		 ES  
    Global end of trial date
    14 Apr 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Mar 2026
    First version publication date
    25 Mar 2026
    Other versions
    Summary report(s)
    		 Resumen del Informe Clínico Final

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CMMo/ICTUS/2013
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02178657
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud
    Sponsor organisation address
    Edificio S-2 Calle Americo Vespucio Nº 15 Parque Cientifico Y Tecnologico Cartuja 93 Sevilla 41092 S, Sevilla, Spain, 41092
    Public contact
    UNIDAD DE COORDINACIÓN-INVESTIGACIÓN CLÍNICA , Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso YSalud, 0034 955048366, ensayosclinicos.radytta.fps@juntadeandalucia.es
    Scientific contact
    UNIDAD DE COORDINACIÓN-INVESTIGACIÓN CLÍNICA , Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso YSalud, 0034 955048366, ensayosclinicos.radytta.fps@juntadeandalucia.es
    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
    04 Sep 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Apr 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Apr 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy in the intra-arterial infusion with mononuclear autologous bone marrow stem cells in patients with ischemic stroke, by the evaluation of the functional recovering after infusion
    Protection of trial subjects
    Trial subject protection measures included prior written informed consent, predefined inclusion and exclusion criteria to minimise risk, close safety monitoring throughout the trial, follow-up of adverse events, and civil liability insurance coverage in accordance with Spanish legislation (Royal Decree 1090/2015) to compensate subjects in the event of trial-related harm.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 77
    Worldwide total number of subjects
    77
    EEA total number of subjects
    77
    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)
    37
    From 65 to 84 years
    40
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment was conducted between 29 April 2015 and 6 May 2021 at participating hospitals. Most patients were enrolled at Hospital Universitario Virgen del Rocío, followed by Hospital Reina Sofía. Hospital Universitario Virgen Macarena and Hospital Puerta del Mar enrolled smaller numbers of patients.

    Pre-assignment
    Screening details
    		 Screening failures (n = 2) Did not meet eligibility criteria (n = 1) Other (n = 1): Inability to perform bone marrow extraction and processing on the same day.

    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
    Blinding implementation details
    This is a double-blind clinical trial, meaning that neither the patient nor the medical team will be aware of the treatment group assignment. Once the 6-month follow-up period of the last enrolled patient has been completed, and under the conditions previously described, unblinding will be authorised. At that point, all patients who were randomised to the control group may be treated under a compassionate use programme.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental group 1
    Arm description
    		 Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 2 × 10⁶ ±10% cells/kg body weight.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Autologous bone marrow adult mononuclear cells not expanded
    Investigational medicinal product code
    PRD11475388
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Infusion
    Dosage and administration details
    Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 2 × 10⁶ ±10% cells/kg body weight. After inclusion in the trial and randomisation, all patients will undergo a catheterisation procedure during which baseline haemodynamic parameters will be assessed and, as appropriate, the cellular product or placebo will be administered via the three main coronary arteries: the left anterior descending, the circumflex, and the right coronary artery, using a microcatheter positioned in the proximal segment of each artery. Fifty percent of the total cell dose will be administered via the left anterior descending artery, and the remaining 50% will be administered via either the right coronary artery or the circumflex artery, depending on coronary dominance. In cases where no clear dominance is present, the cell suspension will be distributed equally between the right coronary and circumflex arteries (25% each). Exceptionally, if the left anterior descending arteries

    Arm title
    		 Experimental group 2
    Arm description
    		 Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 5 × 10⁶ ±10% cells/kg body weight
    Arm type
    		 Experimental

    Investigational medicinal product name
    Autologous bone marrow adult mononuclear cells not expanded
    Investigational medicinal product code
    PRD11475388
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Infusion
    Dosage and administration details
    Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 2 × 10⁶ ±10% cells/kg body weight. After inclusion in the trial and randomisation, all patients will undergo a catheterisation procedure during which baseline haemodynamic parameters will be assessed and, as appropriate, the cellular product or placebo will be administered via the three main coronary arteries: the left anterior descending, the circumflex, and the right coronary artery, using a microcatheter positioned in the proximal segment of each artery. Fifty percent of the total cell dose will be administered via the left anterior descending artery, and the remaining 50% will be administered via either the right coronary artery or the circumflex artery, depending on coronary dominance. In cases where no clear dominance is present, the cell suspension will be distributed equally between the right coronary and circumflex arteries (25% each). Exceptionally, if the left anterior descending arteries

    Arm title
    		 Control group
    Arm description
    		 Without intervention.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Experimental group 1 Experimental group 2 Control group
    Started
    20
    19
    38
    Completed
    20
    19
    38

    Baseline characteristics

    		 Close Top of page

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental group 1
    Reporting group description
    		 Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 2 × 10⁶ ±10% cells/kg body weight.

    Reporting group title
    Experimental group 2
    Reporting group description
    		 Non-expanded autologous adult bone marrow mononuclear cells (CMMo/CMN-BM) at a dose of 5 × 10⁶ ±10% cells/kg body weight

    Reporting group title
    Control group
    Reporting group description
    		 Without intervention.

    Primary: Primary endpoint. Modified Rankin Scale score 0–2.

    		 Close Top of page
    End point title
    		 Primary endpoint. Modified Rankin Scale score 0–2.
    End point description
    To evaluate the efficacy of bone marrow stem cell treatment in patients with acute ischemic stroke by assessing functional recovery following the procedure. The primary study endpoint will be the proportion of patients achieving functional independence (modified Rankin Scale score 0–2) at 6 months of follow-up
    End point type
    Primary
    End point timeframe
    At 6 months of follow-up.
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Number of subjects
    10
    8
    14
    Statistical analysis title
    		 Proportion of Subjects Achieving mRS 0–2. 6 Month
    Statistical analysis description
    The primary efficacy variable is binary (success: mRS 0–2 vs failure: mRS 3–6). The comparison between treatment groups was performed using binary logistic regression with an identity link at 6 months. The common difference in success proportions between groups was calculated with its 95% confidence interval (Wald method) as the measure of clinical effect. In addition, the odds ratio between groups was estimated with its 95% confidence interval using standard logistic regression with a logit lin
    Comparison groups
    Experimental group 1 v Experimental group 2 v Control group
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Wald test
    Confidence interval

    Secondary: Secondary end point. NIH Stroke Scale (NIHSS) - 3 months

    		 Close Top of page
    End point title
    		 Secondary end point. NIH Stroke Scale (NIHSS) - 3 months
    End point description
    Change in NIHSS score from baseline to 3 and 6 months, and comparison of this change between the control and experimental groups.
    End point type
    Secondary
    End point timeframe
    From baseline to 3 and 6 months
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: NIHSS points
        least squares mean (confidence interval 95%)
    5.7 (4.3 to 7.2)
    9 (7.5 to 10.5)
    7 (5.9 to 8.1)
    Statistical analysis title
    		 NIH Stroke Scale (NIHSS)
    Statistical analysis description
    The improvement in the NIHSS score from baseline to 3 and 6 months was evaluated as a quantitative variable using generalized linear mixed models (GLMM), which incorporated the baseline measurement and the post‑treatment assessments, accounting for the distribution and correlation between repeated measures. The treatment effect was expressed as the adjusted mean difference between groups, with 95% confidence intervals and statistical significance evaluated using the Wald method.
    Comparison groups
    Experimental group 1 v Experimental group 2 v Control group
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 > 0.05 [2]
    Method
    		 Wald test within GLMM
    Confidence interval
    Notes
    [1] - Analysis of adjusted mean differences using generalized linear mixed models (GLMM)
    [2] - Wald test from generalized linear mixed model (GLMM) comparing adjusted means.

    Secondary: Secondary end point. NIH Stroke Scale (NIHSS) - 6 months

    		 Close Top of page
    End point title
    		 Secondary end point. NIH Stroke Scale (NIHSS) - 6 months
    End point description
    Change in NIHSS score from baseline to 3 and 6 months, and comparison of this change between the control and experimental groups.
    End point type
    Secondary
    End point timeframe
    From baseline to 3 and 6 months
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: NIHSS points
        least squares mean (confidence interval 95%)
    4.6 (3.2 to 6.1)
    7.9 (6.4 to 9.4)
    6.5 (5.4 to 7.5)
    Statistical analysis title
    		 NIH Stroke Scale (NIHSS)
    Statistical analysis description
    The improvement in the NIHSS score from baseline to 3 and 6 months was evaluated as a quantitative variable using generalized linear mixed models (GLMM), which incorporated the baseline measurement and the post‑treatment assessments, accounting for the distribution and correlation between repeated measures. The treatment eff ect was expressed as the adjusted mean diff erence between groups, with 95% confi dence intervals and statistical signifi cance evaluated using the Wald method.
    Comparison groups
    Experimental group 1 v Experimental group 2 v Control group
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 > 0.05 [4]
    Method
    		 Wald test within GLMM
    Confidence interval
    Notes
    [3] - Analysis of adjusted mean diff erences using generalized linear mixed models (GLMM).
    [4] - Wald test from generalized linear mixed model (GLMM) comparing adjusted means.

    Secondary: Secondary end point. Barthel Index (Barthel >90) - 3 months

    		 Close Top of page
    End point title
    		 Secondary end point. Barthel Index (Barthel >90) - 3 months
    End point description
    End point type
    Secondary
    End point timeframe
    Independence on the Barthel Index (Barthel >90) between baseline and 3 and 6 months, and between the control and experimental groups.
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Subjects
        number (confidence interval 95%)
    8 (4 to 12)
    6 (2 to 10)
    7 (2 to 12)
    No statistical analyses for this end point

    Secondary: Secondary end point. Barthel Index (Barthel >90) - 6 months

    		 Close Top of page
    End point title
    		 Secondary end point. Barthel Index (Barthel >90) - 6 months
    End point description
    End point type
    Secondary
    End point timeframe
    Independence on the Barthel Index (Barthel >90) between baseline and 3 and 6 months, and between the control and experimental groups.
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Subjects
        number (confidence interval 95%)
    3 (0 to 6)
    9 (5 to 13)
    9 (4 to 14)
    No statistical analyses for this end point

    Secondary: Secondary end point. Final infarct volume (FLAIR MRI) at 180 days

    		 Close Top of page
    End point title
    		 Secondary end point. Final infarct volume (FLAIR MRI) at 180 days
    End point description
    Final infarct volume measured on FLAIR MRI at 180 days. Baseline infarct was characterized on diffusion‑weighted MRI (DWI). Given the quantitative nature and high dispersion with potential outliers, between‑group comparisons were performed using quantile regression, reporting adjusted median (and quartile) differences with 95% confidence intervals.
    End point type
    Secondary
    End point timeframe
    Baseline (DWI MRI) and Day 180 (± X days) FLAIR MRI
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: mL
        median (confidence interval 95%)
    44.9 (25.4 to 64.4)
    41.9 (18.5 to 65.3)
    42.3 (30.5 to 54.1)
    No statistical analyses for this end point

    Secondary: Secondary endpoint. Long‑term neurological maintenance. Modified Rankin Scale 0–2 (12)

    		 Close Top of page
    End point title
    		 Secondary endpoint. Long‑term neurological maintenance. Modified Rankin Scale 0–2 (12)
    End point description
    Analysis of the modified Rankin Scale 0–2 and the Barthel Index (>90) at 12 and 24 months to assess long‑term neurological maintenance. Modified Rankin Scale 0–2 at 12 months.
    End point type
    Secondary
    End point timeframe
    12 months.
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Number of subjects
    12
    6
    16
    Statistical analysis title
    		 Proportion of Subjects Achieving mRS 0–2. 12 Month
    Statistical analysis description
    Neurological maintenance, evaluated using mRS 0–2 and Barthel >90 at 12 and 24 months, was analyzed following the same methodology applied to the primary variable. (The primary efficacy variable is binary (success: mRS 0–2 vs failure: mRS 3–6). The comparison between treatment groups was performed using binary logistic regression with an identity link at 6 months. The common difference in success proportions between groups was calculated with its 95% confidence interval (Wald method)).
    Comparison groups
    Experimental group 1 v Experimental group 2 v Control group
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Wald test
    Confidence interval

    Secondary: Secondary endpoint. Long‑term neurological maintenance. Modified Rankin Scale 0–2 (24)

    		 Close Top of page
    End point title
    		 Secondary endpoint. Long‑term neurological maintenance. Modified Rankin Scale 0–2 (24)
    End point description
    Analysis of the modified Rankin Scale 0–2 and the Barthel Index (>90) at 12 and 24 months to assess long‑term neurological maintenance. Modified Rankin Scale 0–2 at 12 months.
    End point type
    Secondary
    End point timeframe
    At 24 months.
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Number of subjects
    11
    6
    18
    Statistical analysis title
    		 Proportion of Subjects Achieving mRS 0–2. 24Months
    Comparison groups
    Experimental group 1 v Experimental group 2 v Control group
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Wald test
    Confidence interval

    Secondary: Secondary endpoint. Long‑term neurological maintenance. Barthel index (>90) (12)

    		 Close Top of page
    End point title
    		 Secondary endpoint. Long‑term neurological maintenance. Barthel index (>90) (12)
    End point description
    Neurological maintenance, assessed using mRS 0–2 and Barthel >90 at 12 and 24 months, was analyzed following the same methodology applied to the primary variable.
    End point type
    Secondary
    End point timeframe
    At 12 months
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Subjects
        number (confidence interval 95%)
    10 (6 to 14)
    4 (1 to 7)
    13 (7 to 19)
    No statistical analyses for this end point

    Secondary: Secondary endpoint. Long‑term neurological maintenance. Barthel index (>90) (24)

    		 Close Top of page
    End point title
    		 Secondary endpoint. Long‑term neurological maintenance. Barthel index (>90) (24)
    End point description
    Neurological maintenance, assessed using mRS 0–2 and Barthel >90 at 12 and 24 months, was analyzed following the same methodology applied to the primary variable.
    End point type
    Secondary
    End point timeframe
    At 24 months
    End point values
    		 Experimental group 1 Experimental group 2 Control group
    Number of subjects analysed
    20
    19
    38
    Units: Subjects
        number (confidence interval 95%)
    11 (7 to 16)
    4 (1 to 8)
    13 (7 to 19)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events occurring at any time after patient inclusion in the study must be reported, that is, from the signing of the informed consent by the subject until 30 days after the patient has completed or withdrawn from the study. A subject is co
    Adverse event reporting additional description
    The investigator / their collaborators will question and/or examine the patient for any signs of adverse events. Patient questioning regarding the possible occurrence of adverse events will be conducted in a general manner. Patients should not be specifically questioned about the presence or absence of particular adverse events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23
    Reporting groups
    Reporting group title
    Control
    Reporting group description
    		 -

    Reporting group title
    Treated, Dose 2 × 10⁶ ±10%
    Reporting group description
    		 -

    Reporting group title
    Treated, Dose 5 × 10⁶ ±10%
    Reporting group description
    		 -

    Serious adverse events
    		 Control Treated, Dose 2 × 10⁶ ±10% Treated, Dose 5 × 10⁶ ±10%
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 39 (35.90%)
    5 / 19 (26.32%)
    10 / 19 (52.63%)
         number of deaths (all causes)
    4
    0
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gallbladder cancer
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post angioplasty restenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Fibromuscular dysplasia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supreventicular tachycardia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischemic attack
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischemic stroke
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Vascular stent stenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Postmenopause
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         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
    Abdominal pain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         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 haemorrhage
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         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 volvulus
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         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: 5%
    Non-serious adverse events
    		 Control Treated, Dose 2 × 10⁶ ±10% Treated, Dose 5 × 10⁶ ±10%
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    36 / 39 (92.31%)
    16 / 19 (84.21%)
    19 / 19 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Gallbladder cancer
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Vulval cancer
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Fibromuscular dysplasia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Haematoma
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Hypertension
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
         occurrences all number
    1
    1
    1
    Hypotension
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1
    Hypovolemic shock
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Polypectomy
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    1
    1
    0
    Stent stenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Social circumstances
    Postmenopause
    Additional description: Counts by treatment received: Control (N = 39); Treated, Dose 2 × 10⁶ ±10% (N = 19); Treated, Dose 5 × 10⁶ ±10% (N = 19)
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    1
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Catarrh
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory failure
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Orthopnea
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Allergic rhinitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Choking sensation
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Wheezing
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Cough
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    3
    0
    1
    Mood altered
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Visual hallucination
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Anxiety
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 19 (10.53%)
    1 / 19 (5.26%)
         occurrences all number
    2
    2
    1
    Apathy
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 19 (15.79%)
    0 / 19 (0.00%)
         occurrences all number
    0
    3
    0
    Depression
         subjects affected / exposed
    3 / 39 (7.69%)
    1 / 19 (5.26%)
    2 / 19 (10.53%)
         occurrences all number
    3
    1
    2
    Depressed mood
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Insomnia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    2
    0
    2
    Middle insomnia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Irritability
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    Depressive symptom
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 19 (15.79%)
    0 / 19 (0.00%)
         occurrences all number
    0
    3
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 19 (15.79%)
    0 / 19 (0.00%)
         occurrences all number
    0
    3
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
         occurrences all number
    0
    3
    0
    Transaminases increased
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
         occurrences all number
    1
    1
    1
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Post procedural haematoma
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Lesion
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Post angioplasty restenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Lupus endocarditis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 19 (5.26%)
    3 / 19 (15.79%)
         occurrences all number
    2
    2
    3
    Myocardial ischaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    Palpitations
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Acute coronary syndrome
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    Tachycardia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    3
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Amnesia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Sciatica
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1
    Memory impairment
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    0
    0
    2
    Epilepsy
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    2
    0
    1
    Muscle spasticity
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    1
    0
    2
    Cerebral artery stenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Ischaemic stroke
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    1
    0
    2
    Syncope
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1
    Shaking
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Balance disorder
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    5 / 19 (26.32%)
         occurrences all number
    2
    0
    5
    Anemia normocytic
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Anemia iron deficiency
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Lymphadenitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    2
    0
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 39 (10.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    2
    0
    2
    Lower abdominal pain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Upper abdominal pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1
    Hematochezia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Short bowel syndrome
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Gastric volvulus
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Photosensitivity reaction
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Hematuria
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1
    Urinary incontinence
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Kidney failure
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    3
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    1
    1
    0
    Pain in extremity
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    1
    1
    0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Urinary tract infection bacterial
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    5 / 39 (12.82%)
    2 / 19 (10.53%)
    4 / 19 (21.05%)
         occurrences all number
    6
    3
    5
    Dental infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
         occurrences all number
    2
    2
    1
    Pneumonia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
         occurrences all number
    0
    0
    4
    Otitis externa
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    2
    1
    0
    Iron deficiency
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    Vitamin B12 decreased
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
         occurrences all number
    0
    1
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Oct 2014
    Substantial Modification 1 – Protocol version dated 11 March 2014
    02 Jun 2015
    Substantial Modification 2 – Protocol version dated 25 February 2015
    01 Jun 2016
    Substantial Modification 3 – Protocol version dated 18 January 2016
    23 May 2017
    Substantial Modification 4 – Protocol version dated 27 March 2017
    04 Nov 2019
    Substantial Modification 5 – Protocol version dated 29 April 2019
    22 Nov 2021
    Substantial Modification 6 – Protocol version dated 11 June 2021
    08 Jul 2022
    Substantial Modification 7 – Protocol version dated 10 June 2022.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/36681446
    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 Mar 30 08:31:19 CEST 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA