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   44334   clinical trials with a EudraCT protocol, of which   7366   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 Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)

    Summary
    EudraCT number
    2019-001363-67
    Trial protocol
    DK   NL   FR   DE   ES   GB  
    Global end of trial date
    31 Jan 2024

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

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    D5241C00001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    151 85, Sodertalje, Sweden,
    Public contact
    Global Clinical Lead, AstraZeneca, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, information.center@astrazeneca.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
    31 Jan 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jan 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of tezepelumab as compared with placebo on COPD exacerbations in subjects with moderate to very severe COPD
    Protection of trial subjects
    The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents (e.g., advertisements) were submitted to an IRB/IEC by the Investigator and reviewed and approved by the IRB/IEC before the study is initiated. The Investigator or his/her representative explained the nature of the study to the subject or his/her legally authorised representative and answered all questions regarding the study. Subjects were informed that their participation was voluntary. Subjects or their legally authorised representative were required to sign a statement of informed consent that met the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study centre. Subjects must have been re-consented to the most current version of the ICF(s) during their participation in the study. A copy of the ICF(s) was provided to the subject or the subject’s legally authorised representative.
    Background therapy
    All subjects were treated with maintenance locally approved triple inhaled therapy (ICS/LABA/LAMA) for COPD for at least 12 months prior to enrolment (Visit 1) with a stable dose of ICS for the 3 months prior to Visit 1.
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Jul 2019
    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
    Korea, Republic of: 33
    Country: Number of subjects enrolled
    Israel: 53
    Country: Number of subjects enrolled
    Germany: 29
    Country: Number of subjects enrolled
    Denmark: 28
    Country: Number of subjects enrolled
    United Kingdom: 26
    Country: Number of subjects enrolled
    Netherlands: 18
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    United States: 70
    Country: Number of subjects enrolled
    Canada: 46
    Worldwide total number of subjects
    333
    EEA total number of subjects
    105
    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)
    113
    From 65 to 84 years
    220
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 80 centres in 10 countries. A total of 579 participants were enrolled of which 337 were randomised. Of the 337 randomised, 333 participants received treatment. 4 participants randomised in error and did not receive treatment. 187 participants not randomised were due to screen failures.

    Pre-assignment
    Screening details
    The study consisted of a screening period for approximately 6 weeks. At the end of the screening period, participants were randomised in 1:1 ratio for tezepelumab or placebo. Randomisation was stratified by region (North America, Europe, Asia), and number of prior exacerbations (2, >=3) recorded at randomisation in IWRS.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Tezepelumab
    Arm description
    420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
    Arm type
    Experimental

    Investigational medicinal product name
    Tezepelumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    420 mg Q4W

    Arm title
    Placebo
    Arm description
    Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Q4W

    Number of subjects in period 1
    Tezepelumab Placebo
    Started
    165
    168
    Completed Treatment
    138 [1]
    138 [2]
    Completed
    146
    150
    Not completed
    19
    18
         Adverse event, serious fatal
    2
    4
         Site Closure
    6
    -
         Consent withdrawn by subject
    8
    11
         Adverse event, non-fatal
    2
    2
         Lost to follow-up
    1
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Number of subjects are correct as reported.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Number of subjects are correct as reported.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Tezepelumab
    Reporting group description
    420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Reporting group title
    Placebo
    Reporting group description
    Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Reporting group values
    Tezepelumab Placebo Total
    Number of subjects
    165 168 333
    Age Categorical
    Age groups in years
    Units: Participants
        Age Group : >=40 - <65
    52 61 113
        Age Group : >=65 - <=80
    113 107 220
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    67.4 ( 6.75 ) 67.1 ( 7.24 ) -
    Sex: Female, Male
    Units: Participants
        Female
    77 68 145
        Male
    88 100 188
    Race/Ethnicity, Customized
    Other also includes Native Hawaiian or Other Pacific Islander and American Indian or Alaska Native categories
    Units: Subjects
        White
    147 146 293
        Black or African American
    2 2 4
        Asian
    16 18 34
        Other
    0 2 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    7 3 10
        Not Hispanic or Latino
    158 165 323
        Unknown or Not Reported
    0 0 0

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Tezepelumab
    Reporting group description
    420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Reporting group title
    Placebo
    Reporting group description
    Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Primary: Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD.

    Close Top of page
    End point title
    Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD.
    End point description
    A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, >=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.
    End point type
    Primary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: exacerbations per year
        least squares mean (confidence interval 90%)
    1.75 (1.45 to 2.11)
    2.11 (1.77 to 2.53)
    Statistical analysis title
    Negative binomial analysis
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1042 [1]
    Method
    Negative Binomial
    Parameter type
    Rate Ratio
    Point estimate
    0.83
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    1.06
    Notes
    [1] - 1-sided p-value

    Secondary: Time to first moderate/severe COPD exacerbation

    Close Top of page
    End point title
    Time to first moderate/severe COPD exacerbation
    End point description
    Time to first moderate/severe COPD exacerbation post-randomisation, presented as number of subjects with at least one moderate/severe COPD exacerbation.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: Participants
    94
    105
    No statistical analyses for this end point

    Secondary: Proportion of participants COPD exacerbation free at Week 52

    Close Top of page
    End point title
    Proportion of participants COPD exacerbation free at Week 52
    End point description
    An exacerbation event was defined as described in primary analysis. A participant was exacerbation free if they did not experience any moderate or severe exacerbations from randomisation to Week 52 (EOT).
    End point type
    Secondary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: participants
    71
    63
    No statistical analyses for this end point

    Secondary: Comparison of annual severe COPD exacerbation rates over 52 weeks

    Close Top of page
    End point title
    Comparison of annual severe COPD exacerbation rates over 52 weeks
    End point description
    An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: exacerbations per year
        least squares mean (confidence interval 90%)
    0.13 (0.07 to 0.24)
    0.25 (0.15 to 0.42)
    No statistical analyses for this end point

    Secondary: Proportion of participants with >=1 severe COPD exacerbations over 52 weeks

    Close Top of page
    End point title
    Proportion of participants with >=1 severe COPD exacerbations over 52 weeks
    End point description
    An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: participants
    16
    22
    No statistical analyses for this end point

    Secondary: Time to first severe COPD exacerbation

    Close Top of page
    End point title
    Time to first severe COPD exacerbation
    End point description
    Time to first severe COPD exacerbation post-randomisation, presented as number of subjects with at least one severe COPD exacerbation.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: Participants
    16
    22
    No statistical analyses for this end point

    Secondary: Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52

    Close Top of page
    End point title
    Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52
    End point description
    Pre-Bronchodilator FEV1 (L) was determined by spirometry at the clinic visit. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. Change from baseline was obtained as an absolute difference between Week 52 measure and the baseline value. Baseline was defined as the last assessment recorded prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    163
    166
    Units: Liters
        least squares mean (standard error)
    0.026 ( 0.015 )
    -0.029 ( 0.015 )
    No statistical analyses for this end point

    Secondary: Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52

    Close Top of page
    End point title
    Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52
    End point description
    The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Baseline is the measurement recorded at Week 0 (Visit 3).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    157
    156
    Units: units on a scale
        least squares mean (standard error)
    -4.796 ( 1.176 )
    -1.863 ( 1.189 )
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving a minimum clinically important difference of 4 units or more in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52

    Close Top of page
    End point title
    Proportion of participants achieving a minimum clinically important difference of 4 units or more in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52
    End point description
    The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. A responder was defined as an individual who had "improvement" at Week 52 (>=4 point decrease in SGRQ total score).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    163
    163
    Units: participants
    65
    59
    No statistical analyses for this end point

    Secondary: Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52

    Close Top of page
    End point title
    Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52
    End point description
    The CAT is an 8-item PRO developed to measure the impact of COPD on health status. A CAT total score is the sum of item responses. Scores range from 0-40 with higher scores indicative of greater COPD impact on health status. Baseline was defined as the value at the randomisation visit (Visit 3). If the Visit 3 measurement was missing, the screening value was used as baseline instead.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    159
    162
    Units: units on a scale
        least squares mean (standard error)
    -3.037 ( 0.524 )
    -1.182 ( 0.524 )
    No statistical analyses for this end point

    Secondary: Serum concentration of Tezepelumab

    Close Top of page
    End point title
    Serum concentration of Tezepelumab
    End point description
    Blood samples were collected to determine the serum concentration of Tezepelumab. With the exception of Week 0 and Week 64, only pre-dose data from samples collected between 21 and 35 days after previous dose of investigational product were included. Week 0 arithmetic mean values are below the lower limit of quantification (LLOQ). The LLOQ is 0.010 micrograms per milliliter.
    End point type
    Secondary
    End point timeframe
    Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    162
    0 [2]
    Units: microgram per milliliter (mg/mL)
    arithmetic mean (standard deviation)
        Week 0
    0 ( 0 )
    ( )
        Week 4
    25.881 ( 11.8828 )
    ( )
        Week 12
    44.316 ( 19.0716 )
    ( )
        Week 24
    49.093 ( 21.2414 )
    ( )
        Week 36
    48.667 ( 22.2241 )
    ( )
        Week 52
    52.659 ( 26.1703 )
    ( )
        Follow-up Week 64
    6.602 ( 6.1832 )
    ( )
    Notes
    [2] - Not applicable since it is not the experimental product.
    No statistical analyses for this end point

    Secondary: Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab

    Close Top of page
    End point title
    Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab
    End point description
    Blood samples were measured for the presence of ADAs for tezepelumab using validated assays. Treatment-induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4 fold or higher level following IP administration. TE-ADA positive was defined as the sum of treatment-induced ADA positive and treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. ADA persistently positive was defined as ADA positive at >= 2 post-baseline assessments or ADA positive at last post-baseline assessment. ADA transiently positive was defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of ADA persistently positive. Treatment-induced nAb positive was defined as nAb negative or ADA negative at baseline and nAb positive at any post-baseline visit.
    End point type
    Secondary
    End point timeframe
    Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
    End point values
    Tezepelumab Placebo
    Number of subjects analysed
    165
    168
    Units: Participants
        ADA positive at baseline and/or post-baseline
    10
    19
        Any baseline ADA positive
    5
    8
        Only baseline ADA positive
    2
    1
        Any post-baseline ADA positive
    8
    18
        Baseline and at least 1 post-baseline ADA positive
    3
    7
        Treatment-induced ADA positive
    5
    11
        Treatment-boosted ADA positive
    0
    0
        TE-ADA positive (ADA incidence)
    5
    11
        ADA persistently positive
    5
    15
        ADA transiently positive
    3
    3
        nAb positive at baseline and/or post-baseline
    0
    0
        Treatment-induced nAb positive (nAb incidence)
    0
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until end of study at Week 64.
    Adverse event reporting additional description
    All AE data is based off the Safety Analysis Set, which includes all subjects who received at least one dose of study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Teze 420 mg Q4W
    Reporting group description
    420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Reporting group title
    Placebo
    Reporting group description
    Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

    Serious adverse events
    Teze 420 mg Q4W Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 165 (33.94%)
    58 / 168 (34.52%)
         number of deaths (all causes)
    3
    6
         number of deaths resulting from adverse events
    3
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal melanoma
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage II
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage I
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal squamous cell carcinoma stage IV
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal adenocarcinoma stage IV
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer metastatic
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coeliac artery occlusion
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery dissection
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Vascular stent stenosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 165 (0.61%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 165 (1.21%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    20 / 165 (12.12%)
    26 / 168 (15.48%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 39
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 165 (1.21%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Limb traumatic amputation
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural dizziness
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Left ventricular failure
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    2 / 165 (1.21%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Angina pectoris
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 165 (0.61%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 165 (1.21%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 165 (1.21%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Alcoholic pancreatitis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    2 / 165 (1.21%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis alcoholic
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 165 (0.61%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal artery occlusion
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 165 (0.61%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Herpes zoster
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 165 (1.21%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 165 (0.61%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 165 (1.21%)
    3 / 168 (1.79%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 165 (4.24%)
    5 / 168 (2.98%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    3 / 165 (1.82%)
    3 / 168 (1.79%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 165 (0.61%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas bronchitis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 165 (0.00%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Teze 420 mg Q4W Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    78 / 165 (47.27%)
    56 / 168 (33.33%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    11 / 165 (6.67%)
    10 / 168 (5.95%)
         occurrences all number
    12
    12
    Contusion
         subjects affected / exposed
    10 / 165 (6.06%)
    0 / 168 (0.00%)
         occurrences all number
    11
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 165 (7.27%)
    5 / 168 (2.98%)
         occurrences all number
    13
    5
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 165 (5.45%)
    1 / 168 (0.60%)
         occurrences all number
    11
    1
    Headache
         subjects affected / exposed
    3 / 165 (1.82%)
    10 / 168 (5.95%)
         occurrences all number
    4
    24
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    11 / 165 (6.67%)
    8 / 168 (4.76%)
         occurrences all number
    11
    8
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 165 (5.45%)
    4 / 168 (2.38%)
         occurrences all number
    10
    4
    Infections and infestations
    COVID-19
         subjects affected / exposed
    25 / 165 (15.15%)
    16 / 168 (9.52%)
         occurrences all number
    26
    17
    Nasopharyngitis
         subjects affected / exposed
    17 / 165 (10.30%)
    9 / 168 (5.36%)
         occurrences all number
    18
    9
    Urinary tract infection
         subjects affected / exposed
    5 / 165 (3.03%)
    10 / 168 (5.95%)
         occurrences all number
    6
    12

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Mar 2022
    Added “Tezepelumab has been well tolerated with an acceptable safety profile and no safety signals in subjects with severe, uncontrolled asthma identified in the completed studies to date.” to Benefit/Risk Assessment. Added to Medical Devices: regarding sponsor manufactured medical device use in this study and all medical device deficiencies should be documented and reported by investigator through the study. Added definitions of medical device deficiency and requirements to fulfil regulatory reporting obligations worldwide and investigator's responsibility for detection and documentation of events meeting the definition of device deficiency occurring during the study. Added Appendix J - Medical device AEs, ADEs, SAEs, SADEs, US ADEs and Medical Device Deficiencies: Definitions and Procedures for Recording, Evaluating and Follow-up.
    18 Oct 2022
    Added serious cardiac events as an event requiring adjudication. Added that the IAC will assess whether there is a causal relationship between IP use and MACE events, serious cardiac events, and deaths. “Important potential risks” added including serious infections, malignancies, and serious cardiac events; “Potential risks" added including serious hypersensitivity reactions, and helminth infections; “Study procedures” added including COVID 19. Added new AESI: ‘Serious cardiac events’. Removed “Injection Site reactions”. Replaced “Anaphylactic reactions” and “Immune complex disease (Type III hypersensitivity reactions)” with “Serious hypersensitivity reactions”. Replaced “Severe infections” and Opportunistic infections” with “Serious infections”, and added a footnote clarifying when to complete the eCRF Severe infection pages.

    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 May 05 01:46:47 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA