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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   40995   clinical trials with a EudraCT protocol, of which   6701   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    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:
    Open, multicentre study on the equivalent efficacy and safety of Botulinum toxin A (500 Units Dysport®) in the treatment of heterogeneous forms of cervical dystonia

    Summary
    EudraCT number
    2004-002086-20
    Trial protocol
    AT  
    Global end of trial date
    04 Apr 2008

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Mar 2016
    First version publication date
    11 Mar 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    A-94-52120-098
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    IPSEN PHARMA GmbH
    Sponsor organisation address
    Willy-Brandt-Straße 3, Ettlingen, Germany, D-76275
    Public contact
    Medical Director, Neurology, Ipsen, clinical.trials@ipsen.com
    Scientific contact
    Medical Director, Neurology, Ipsen, clinical.trials@ipsen.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
    22 Dec 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Feb 2008
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Apr 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The results of a dose finding study have shown that 500 units Dysport® are the optimal starting dose for the treatment of patients with rotational torticollis. Although Dysport is an established first-line neurological treatment for cervical dystonia since its registration in Germany in 1995, there are only little data available on dose, efficacy and safety in the treatment of heterogeneous forms of cervical dystonia. The aim of this multicentre open study is to demonstrate the equivalent efficacy and safety in the treatment of the two most frequent forms of cervical dystonia (predominantly rotational torticollis and predominantly laterocollis) with the standard initial dose of 500 units Dysport.
    Protection of trial subjects
    This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations(including European Directive 2001/20/EC), and with the ethical principles laid down in the Declaration of Helsinki. The clinical trial was performed taking into account the German Medicinal Product Act (AMG). The study was submitted to the Federal Institute for Drugs and Medical Devices (BfArM) and to the responsible regulatory authorities. The patients participating in the study were insured in accordance with the provisions of the German Drug Law (AMG, in particular §40 paragraph 3).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Oct 2004
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 16
    Country: Number of subjects enrolled
    Germany: 500
    Worldwide total number of subjects
    516
    EEA total number of subjects
    516
    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)
    409
    From 65 to 84 years
    106
    85 years and over
    1

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    First subject enrolled on 28October2004. To conduct the study 105 German and 5 Austrian centres were selected.

    Pre-assignment
    Screening details
    516 Subjects were enrolled to study. Due to non-availability of safety data, one subject was excluded. The Intention-To-Treat population (ITT) consisted of 515 subjects.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Dysport 500 units
    Arm description
    Predominantly rotatory torticollis & Laterocollis: treatment with a single dose of 500 units Dysport®
    Arm type
    Experimental

    Investigational medicinal product name
    Dysport
    Investigational medicinal product code
    Other name
    Clostridium botulinum Toxin Type A
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    A single injection with 500 units Dysport®, diluted in 2.5 ml 0.9 % NaCl (= 200 units / ml), administered by intramuscular injections according to an injection protocol with optional follow-up injection at week 12.

    Number of subjects in period 1 [1]
    Dysport 500 units
    Started
    515
    Completed
    489
    Not completed
    26
         Lack of efficacy
    2
         Discontinuation of drug therapy by investigator
    1
         Unspecified
    7
         Consent withdrawn by subject
    1
         Insufficient compliance
    6
         Lost to follow-up
    9
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Worldwide numbers reported are per all treated 516 subjects. However, baseline period is per 515 Safety population subjects (includes all patients who received the study medication and for whom any safety data were recorded). Due to non-availability of safety data one subject was excluded from safety population.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dysport 500 units
    Reporting group description
    Predominantly rotatory torticollis & Laterocollis: treatment with a single dose of 500 units Dysport®

    Reporting group values
    Dysport 500 units Total
    Number of subjects
    515 515
    Age categorical
    Units: Subjects
        < 30
    24 24
        30 to < 40
    60 60
        40 to < 50
    147 147
        50 to < 60
    126 126
        60 to < 70
    112 112
        70 to < 80
    43 43
        ≥ 80
    3 3
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    51.9 ± 12.7 -
    Gender categorical
    Units: Subjects
        Female
    353 353
        Male
    162 162
    Race
    Units: Subjects
        Caucasian
    511 511
        Asian
    1 1
        Oriental
    3 3
    BMI
    The Safety population includes all patients who received the study medication and for whom any safety data were recorded n=510, Body mass index (BMI)
    Units: kg/m²
        arithmetic mean (standard deviation)
    25.3 ± 4.4 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Dysport 500 units
    Reporting group description
    Predominantly rotatory torticollis & Laterocollis: treatment with a single dose of 500 units Dysport®

    Subject analysis set title
    Treatment Group: Rotatory torticollis
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Rotatory torticollis is a subset group

    Subject analysis set title
    Treatment Group: Laterocollis
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Laterocollis is a subset group

    Primary: Change from baseline in the total score of the Tsui rating scale (patient in sitting position)

    Close Top of page
    End point title
    Change from baseline in the total score of the Tsui rating scale (patient in sitting position)
    End point description
    The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: • Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0–9 points) • Subscore B: duration of movement (values 1 or 2) • Subscore C: severity and duration of shoulder elevation (range: 0–3 points) • Subscore D: severity and duration of tremor (range: 0–4 points) The total score was to be calculated as follows: total score = subscores (A x B) + C + D The total score ranges between 0 and 25 points. A high (low) total score represents severe (mild) CD. The ITT population includes all patients of the Safety population with a baseline (visit 1, week 0) and a post-baseline (visit 2, week 4 or visit 3, week 12) assessment of the Tsui rating scale.
    End point type
    Primary
    End point timeframe
    From Baseline (visit 1) to the first on-treatment visit [visit 2 (week 4)/visit 3 (week 12)]
    End point values
    Dysport 500 units Treatment Group: Rotatory torticollis Treatment Group: Laterocollis
    Number of subjects analysed
    503
    396
    107
    Units: Score of the Tsui rating scale
    arithmetic mean (standard deviation)
        Baseline (V1)
    8.4 ± 3.5
    8.4 ± 3.5
    8.3 ± 3.3
        First on-treatment measurement (V2/V1)
    4.6 ± 3.1
    4.6 ± 3.2
    4.3 ± 2.6
        First on-treatment measurement - Baseline (V2-V1)
    -3.8 ± 3.1
    -3.8 ± 3.3
    -4 ± 2.6
    Statistical analysis title
    Rotatory torticollis vs Laterocollis
    Statistical analysis description
    ANCOVA model includes the baseline total Tsui score (patient in sitting position) as covariate (p < 0.0001) and the main type of CD as between-group factor (due to non-significance the interaction between baseline total Tsui score and the main type of CD was removed from the model)
    Comparison groups
    Treatment Group: Rotatory torticollis v Treatment Group: Laterocollis
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    other [1]
    P-value
    = 0.2552
    Method
    ANCOVA
    Confidence interval
    Notes
    [1] - Exploratory analysis

    Secondary: Tsui subscores (patient in sitting position)

    Close Top of page
    End point title
    Tsui subscores (patient in sitting position)
    End point description
    The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: • Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0–9 points) • Subscore B: duration of movement (values 1 or 2) • Subscore C: severity and duration of shoulder elevation (range: 0–3 points) • Subscore D: severity and duration of tremor (range: 0–4 points) The total score was to be calculated as follows: total score = subscores (A x B) + C + D The total score ranges between 0 and 25 points. A high (low) total score represents severe (mild) CD. The ITT population includes all patients of the Safety population with a baseline (visit 1, week 0) and a post-baseline (visit 2, week 4 or visit 3, week 12) assessment of the Tsui rating scale.
    End point type
    Secondary
    End point timeframe
    At Baseline (visit 1), first on-treatment visit [visit 2 (week 4) / visit 3 (week 12)], V2 minus V1, V3 minus V1
    End point values
    Dysport 500 units
    Number of subjects analysed
    503
    Units: score of the Tsui rating scale
    arithmetic mean (standard deviation)
        Subscore A: V1 (n=396)
    3.5 ± 1.4
        Subscore A: V2 (n=394)
    2.2 ± 1.4
        Subscore A: V3 (n=386)
    2.7 ± 1.5
        Subscore A:V2 minus V1 (N= 500)
    -1.4 ± 1.3
        Subscore A:V3 minus V1 (N= 490)
    -0.8 ± 1.3
        Subscore B: V1 (n=396)
    1.8 ± 0.4
        Subscore B: V2 (n=394)
    1.4 ± 0.6
        Subscore B: V3 (n=386)
    1.6 ± 0.5
        Subscore B:V2 minus V1 (N= 500)
    -0.3 ± 0.6
        Subscore B:V3 minus V1 (N= 490)
    -0.2 ± 0.5
        Subscore c: V1 (n=396)
    0.9 ± 0.9
        Subscore C: V2 (n=394)
    0.6 ± 0.8
        Subscore C: V3 (n=386)
    0.7 ± 0.8
        Subscore C:V2 minus V1 (N= 500)
    -0.4 ± 0.8
        Subscore C:V3 minus V1 (N= 490)
    -0.2 ± 0.8
        Subscore D: V1 (n= 396)
    1.2 ± 1.3
        Subscore D: V2 (n=394)
    0.6 ± 0.7
        Subscore D: V3 (n= 386)
    0.8 ± 0.9
        Subscore D:V2 minus V1 (N= 500)
    -0.6 ± 1
        Subscore D:V3 minus V1 (N= 490)
    -0.4 ± 0.9
    No statistical analyses for this end point

    Secondary: Change from baseline in CDQ total score and subscores

    Close Top of page
    End point title
    Change from baseline in CDQ total score and subscores
    End point description
    The Craniocervical Dystonia Questionnaire (CDQ-24) is a disease-specific QoL instrument and was to be assessed at visits 1 to 3. It consists of 24 items investigating problems in daily living skills related to CD. This instrument is based on 5 subscales: • Stigma (items 7, 8, 9, 10, 18, 22) • Emotional well-being (items 11, 12, 13, 14, 15) • Pain (items 4, 5, 21) • Activities of daily living (ADL, items 1, 2, 3, 6, 19, 20) • Social / family life (items 16, 17, 23, 24) There are five possible answers to each item representing increasing severity of impairment (scores 0 to 4). In order to obtain scores of the individual subscales, the total score of each subscale (sum of the individual item scores) was transformed linearly to a 0 to 100 scale, where a score of 0 indicates the best The ITT population includes all patients of the Safety population with a baseline (visit 1, week 0) and a post-baseline (visit 2, week 4 or visit 3, week 12) assessment of the Tsui rating scale.
    End point type
    Secondary
    End point timeframe
    From Baseline (visit 1) to visit 2 (week 4), visit 3 (week 12).
    End point values
    Dysport 500 units
    Number of subjects analysed
    503
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Total score: V2 minus V1 (N=484)
    -11.1 ± 16.1
        Total score: V3 minus V1 (N=474)
    -11.8 ± 14.6
        Stigma: V2 minus V1 (N=485)
    -16.8 ± 24
        Stigma: V3 minus V1 (N=476)
    -16.4 ± 22.5
        Emotional well-being: V2 minus V1 (N=485)
    -10.3 ± 19.9
        Emotional well-being: V3 minus V1 (N=476)
    -11.1 ± 18.7
        Pain: V2 minus V1 (N=491)
    -11.5 ± 27.8
        Pain: V3 minus V1 (N=484)
    -13.2 ± 25.5
        Activities of daily living: V2 minus V1 (N=483)
    -11.1 ± 19.6
        Activities of daily living: V3 minus V1 (N=474)
    -12.5 ± 18.6
        Social / family life: V2 minus V1 (N=481)
    -5.6 ± 17.9
        Social / family life: V3 minus V1 (N=469)
    -6.7 ± 17.8
    No statistical analyses for this end point

    Secondary: Change from baseline in the items of the patient dairy based on Day-to-day functions and activities, Pain and duration of pain.

    Close Top of page
    End point title
    Change from baseline in the items of the patient dairy based on Day-to-day functions and activities, Pain and duration of pain.
    End point description
    The ITT population includes all patients of the Safety population with a baseline (visit 1, week 0) and a post-baseline (visit 2, week 4 or visit 3, week 12) assessment of the Tsui rating scale. The weekly recorded patient diary consists of the three items “Day-to-Day Capacities and Activities”, “Pain” and “Duration of Pain”. Each item was rated by the patient on an 11-point scale ranging from 0 = no problems at all to 10 = most severe problems (the actual wording is adapted to each item in question).
    End point type
    Secondary
    End point timeframe
    From Baseline (visit 1) to visit 2 (week 4), visit 3 (week 12).
    End point values
    Dysport 500 units
    Number of subjects analysed
    503
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Day-to-day functions & activities: W4-W0 (N=454)
    -1.1 ± 3
        Day-to-day functions & activities: W12-W0 (N=384)
    -1.1 ± 2.6
        Pain: W4-W0 (N= 452)
    -0.8 ± 2.7
        Pain: W12-W0 (N=383)
    -0.9 ± 2.5
        Duration of pain: W4-W0 (N=451)
    -1.2 ± 2.9
        Duration of pain: W12-W0 (N=382)
    -1.3 ± 2.7
    No statistical analyses for this end point

    Secondary: Number of subjects without pain and/or with a pain reduction based on Global assessment of pain by investigator and patient

    Close Top of page
    End point title
    Number of subjects without pain and/or with a pain reduction based on Global assessment of pain by investigator and patient
    End point description
    The ITT population includes all patients of the Safety population with a baseline (visit 1, week 0) and a post-baseline (visit 2, week 4 or visit 3, week 12) assessment of the Tsui rating scale. At visits 2 and 3 investigators and patients had to assess change of global pain according to the following response categories: 1 = no pain (anymore) 2 = less pain 3 = no change 4 = more pain
    End point type
    Secondary
    End point timeframe
    'Visits 2 and 3 by Investigator and Visits 2 and 3 by Patient'
    End point values
    Dysport 500 units
    Number of subjects analysed
    503
    Units: number of patients
        Investigator: No pain V2
    131
        Investigator: No pain V3
    142
        Investigator: Less pain V2
    205
        Investigator: Less pain V3
    227
        Investigator: No change V2
    94
        Investigator: No change V3
    87
        Investigator: More pain V2
    70
        Investigator: More pain V3
    33
        Patient: No pain V2
    128
        Patient: No pain V3
    132
        Patient: Less pain V2
    202
        Patient: Less pain V3
    231
        Patient: No change V2
    82
        Patient: No change V3
    83
        Patient: More pain V2
    88
        Patient: More pain V3
    44
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to week 12
    Adverse event reporting additional description
    Treatment with a single dose of 500 units Dysport®
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.1
    Reporting groups
    Reporting group title
    Dysport 500 units
    Reporting group description
    'Treatment with a single dose of 500 units Dysport®' as suggested by study team and highlight the change.

    Serious adverse events
    Dysport 500 units
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 515 (2.14%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary congestion
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Apathy
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Depression
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Peritonitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Dysport 500 units
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    206 / 515 (40.00%)
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Hypertension
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    4
    Orthostatic hypotension
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Thrombophlebitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Surgical and medical procedures
    Limb operation
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Facial pain
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Fatigue
         subjects affected / exposed
    6 / 515 (1.17%)
         occurrences all number
    6
    Gait disturbance
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    General physical health deterioration
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Influenza like illness
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Injection site pain
         subjects affected / exposed
    7 / 515 (1.36%)
         occurrences all number
    7
    Injection site paraesthesia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Local swelling
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Malaise
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Sensation of foreign body
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Thirst
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Anxiety disorder
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Conversion disorder
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Depression
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Initial insomnia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Middle insomnia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Panic attack
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Psychotic disorder
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Restlessness
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Investigations
    Blood pressure diastolic increased
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Blood pressure increased
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Blood pressure orthostatic abnormal
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Coronary artery disease
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Tachycardia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Cough
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Dyspnoea
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Rhinitis allergic
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Throat irritation
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Nervous system disorders
    Burning sensation
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    4
    Cervical root pain
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Disturbance in attention
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Dizziness
         subjects affected / exposed
    12 / 515 (2.33%)
         occurrences all number
    13
    Dysarthria
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    4
    Head discomfort
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Head titubation
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    2
    Headache
         subjects affected / exposed
    17 / 515 (3.30%)
         occurrences all number
    21
    Hypoaesthesia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Mastication disorder
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Migraine
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Neuritis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Paraesthesia
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    4
    Paralysis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Paresis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Restless legs syndrome
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Speech disorder
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Tongue paralysis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Tremor
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Eye disorders
    Blepharitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Dry eye
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Eyelid ptosis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Glaucoma
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Keratoconjunctivitis sicca
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Vision blurred
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Ear and labyrinth disorders
    Sudden hearing loss
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Tinnitus
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Vertigo
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    5
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Abdominal pain upper
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Constipation
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Dental caries
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    4 / 515 (0.78%)
         occurrences all number
    4
    Dry mouth
         subjects affected / exposed
    6 / 515 (1.17%)
         occurrences all number
    6
    Dysphagia
         subjects affected / exposed
    51 / 515 (9.90%)
         occurrences all number
    51
    Gastritis
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Gastrointestinal pain
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Toothache
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Haematuria
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Nephritis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Eczema
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    2
    Hyperhidrosis
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Pruritus
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Pruritus generalised
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    3
    Urticaria
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 515 (0.97%)
         occurrences all number
    5
    Arthritis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Back pain
         subjects affected / exposed
    8 / 515 (1.55%)
         occurrences all number
    8
    Bursitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Joint range of motion decreased
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Joint stiffness
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Muscle spasms
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Muscular weakness
         subjects affected / exposed
    70 / 515 (13.59%)
         occurrences all number
    70
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Musculoskeletal disorder
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Musculoskeletal pain
         subjects affected / exposed
    12 / 515 (2.33%)
         occurrences all number
    9
    Musculoskeletal stiffness
         subjects affected / exposed
    5 / 515 (0.97%)
         occurrences all number
    5
    Myalgia
         subjects affected / exposed
    8 / 515 (1.55%)
         occurrences all number
    9
    Neck pain
         subjects affected / exposed
    34 / 515 (6.60%)
         occurrences all number
    35
    Osteoarthritis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    2
    Pain in extremity
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    4
    Pain in jaw
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Trismus
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Infections and infestations
    Acute tonsillitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Cystitis
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    3
    Device related infection
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Eye infection viral
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Herpes simplex
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Herpes zoster
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Hordeolum
         subjects affected / exposed
    2 / 515 (0.39%)
         occurrences all number
    2
    Laryngitis
         subjects affected / exposed
    3 / 515 (0.58%)
         occurrences all number
    4
    Nasopharyngitis
         subjects affected / exposed
    19 / 515 (3.69%)
         occurrences all number
    20
    Otitis media
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    2
    Sinusitis
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 515 (0.19%)
         occurrences all number
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Mar 2006
    Amendments to the study protocol leading to new versions of the study protocol contains :- • Duration of the study : Approx. 3.5 years. • Data Monitoring : A statistical data review will be performed after completion of the first 200 patients. In accordance with the ICH E9 Guideline, Item 4.1, a so-called "Trial Monitoring" or "Data Monitoring" is recommended to evaluate and confirm the quality of the conduct of the study. To prevent jeopardizing the power of the study and/or bias, no efficacy data will be analyzed and no analyses stratified by indication group will be performed. Only initial values, demographic data, distribution of indication groups, protocol violations, withdrawal rate etc, will be descriptively analyzed. Safety data, that is adverse events, will be encoded according to MedDRA, version 9.0, and appropriately analyzed.

    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, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA