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   43873   clinical trials with a EudraCT protocol, of which   7292   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:
    Prospective, double-blind, placebo-controlled, randomized, parallel-group, multi-center study with an open-label extension period to investigate the efficacy and safety of two different doses of NT 201 in Botulinum toxin treatment-naïve subjects with blepharospasm

    Summary
    EudraCT number
    		 2012-004821-26
    Trial protocol
    		 GR  
    Global end of trial date
    10 Nov 2016

    Results information
    Results version number
    		 v2(current)
    This version publication date
    11 Apr 2018
    First version publication date
    23 Nov 2017
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Changes to endpoint descriptions to make it match with CTgov results entries

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MRZ60201_3074_1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01896895
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merz Pharmaceuticals GmbH
    Sponsor organisation address
    Eckenheimer Landstrasse 100, Frankfurt/M, Germany, 60318
    Public contact
    Public Disclosure Manager, Merz Pharmaceuticals GmbH, +49 69 1503 1, clinicaltrials@merz.de
    Scientific contact
    Public Disclosure Manager, Merz Pharmaceuticals GmbH, +49 69 1503 1, clinicaltrials@merz.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Mar 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to investigate the efficacy and safety of two different doses of IncobotulinumtoxinA (NT 201) compared to placebo in one double-blind cycle Main Period (MP) with one subsequent open-label treatment cycle Open label Extension (OLEX period) in botulinum toxin [BTX] treatment-naïve subjects with benign essential blepharospasm (BEB) using a dose of 12.5 or 25 units IncobotulinumtoxinA per eye (total dose of 25 or 50 units IncobotulinumtoxinA for both eyes) in the MP and a single dose of up to 35 units IncobotulinumtoxinA per eye in the OLEX period (total dose of up to 70 units IncobotulinumtoxinA for both eyes), each followed by 6 to 20 weeks observation.
    Protection of trial subjects
    High medical and ethical standards were followed in accordance with Good Clinical Practice and other applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Jan 2014
    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
    Malaysia: 17
    Country: Number of subjects enrolled
    Sri Lanka: 30
    Country: Number of subjects enrolled
    Greece: 14
    Worldwide total number of subjects
    61
    EEA total number of subjects
    14
    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)
    44
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The clinical study was conducted at 5 sites in Malaysia, 4 sites in Sri Lanka and 3 sites in Greece from 21 January 2014 to 10 November 2016.

    Pre-assignment
    Screening details
    		 A total of 68 subjects were screened, 61 were enrolled and treated of which 55 completed the double-blind MP. 39 subjects from the double-blind MP entered the OLEX period and completed the study.

    Period 1
    Period 1 title
    Double-blind MP
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Double-blind MP: Placebo
    Arm description
    		 Subjects received 1.0 milliliter (mL) placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.

    Arm title
    		 Double-blind MP: IncobotulinumtoxinA 25 Units
    Arm description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IncobotulinumtoxinA
    Investigational medicinal product code
    NT 201
    Other name
    Xeomin; Botulinum toxin type A (150 kiloDalton) free from complexing proteins
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.

    Arm title
    		 Double-blind MP: IncobotulinumtoxinA 50 Units
    Arm description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IncobotulinumtoxinA
    Investigational medicinal product code
    NT 201
    Other name
    Xeomin; Botulinum toxin type A (150 kiloDalton) free from complexing proteins
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.

    Number of subjects in period 1
    		Double-blind MP: Placebo Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Started
    20
    22
    19
    Completed
    19
    20
    16
    Not completed
    1
    2
    3
         Consent withdrawn by subject
    -
    2
    1
         Physician decision
    -
    -
    1
         Lost to follow-up
    1
    -
    1
    Period 2
    Period 2 title
    Open Label Extension (OLEX) Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 OLEX: IncobotulinumtoxinA 70 Units
    Arm description
    		 Subjects received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IncobotulinumtoxinA
    Investigational medicinal product code
    NT 201
    Other name
    Xeomin; Botulinum toxin type A (150 kiloDalton) free from complexing proteins
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session (up to 35 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the OLEX Period.

    Number of subjects in period 2 [1]
    		OLEX: IncobotulinumtoxinA 70 Units
    Started
    39
    Completed
    39
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all subjects who completed the double-blind MP fulfilled the eligibility criteria forinclusion into the OLEX period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Double-blind MP: Placebo
    Reporting group description
    		 Subjects received 1.0 milliliter (mL) placebo.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 25 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 50 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session.

    Reporting group values
    		 Double-blind MP: Placebo Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units Total
    Number of subjects
    		 20 22 19 61
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 17 13 14 44
        From 65-84 years
    		 3 9 5 17
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.4 ± 12.01 55.8 ± 15.70 53.5 ± 13.82 -
    Gender categorical
    Units: Subjects
        Female
    		 12 11 13 36
        Male
    		 8 11 6 25
    Race
    Units: Subjects
        White
    		 4 6 4 14
        Asian
    		 16 16 15 47
    Height
    Units: centimeter (cm)
        arithmetic mean (standard deviation)
    		 160.9 ± 9.79 159.6 ± 12.00 158.6 ± 6.74 -
    Weight
    Units: kilogram (kg)
        arithmetic mean (standard deviation)
    		 61.6 ± 16.20 61.0 ± 18.45 63.1 ± 8.70 -
    Body mass index (BMI)
    Units: kilogram per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    		 23.6 ± 5.03 23.6 ± 5.27 25.2 ± 3.33 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Double-blind MP: Placebo
    Reporting group description
    		 Subjects received 1.0 milliliter (mL) placebo.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 25 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 50 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session.
    Reporting group title
    OLEX: IncobotulinumtoxinA 70 Units
    Reporting group description
    		 Subjects received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session.

    Subject analysis set title
    Full Analysis Set (FAS) of Double-blind MP
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set (FAS) is the subset of subjects in the safety evaluation set (SES) of the double-blind MP for whom at least a baseline value of the Jankovic Rating Scale (JRS) severity subscore is available.

    Primary: Double-blind MP: Change from Baseline in JRS Severity Subscore at Day 43 (Visit 4)

    		 Close Top of page
    End point title
    		 Double-blind MP: Change from Baseline in JRS Severity Subscore at Day 43 (Visit 4)
    End point description
    JRS severity subscore was used to classify individual symptoms of blepharospasm and to determine therapeutic efficacy. JRS severity subscore ranges from 0 to 4, where 0: None; 1: increased blinking present with external stimuli; 2: Mild but spontaneous eyelid fluttering, definitely noticeable, possibly embarrassing, but not functionally disabling, 3: Moderate, very noticeable spasm of eyelids only, mildly incapacitating, 4: Severe, incapacitating spasm of eyelids and possibly other facial muscles. Values represent least square (LS) mean differences between baseline and visit 4 resulting from analysis of covariance (ANCOVA) with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates and missings replaced using the last observation carried forward (LOCF) method. Negative values denote improvement, while positive values denote deterioration vs. baseline.
    End point type
    Primary
    End point timeframe
    Baseline, Day 43 (Visit 4)
    End point values
    		 Double-blind MP: Placebo Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Number of subjects analysed
    20 [1]
    22 [2]
    19 [3]
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.6 (-1.0 to -0.1)
    -1.0 (-1.5 to -0.6)
    -1.8 (-2.3 to -1.3)
    Notes
    [1] - FAS
    [2] - FAS
    [3] - FAS
    Statistical analysis title
    		 Visit 4: IncobotulinumtoxinA 50 Units Vs Placebo
    Statistical analysis description
    The difference in change of JRS severity subscore between treatment groups was analyzed by an ANCOVA according to a hierarchical test procedure. First step of hierarchy is hypothesis of superiority of 50 unit dose group NT 201 compared to placebo. This was tested confirmatory (α=0.05, 2-sided) by an ANCOVA with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates based on LS means comparison. Missing values were imputed by LOCF.
    Comparison groups
    Double-blind MP: IncobotulinumtoxinA 50 Units v Double-blind MP: Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 -0.6
    Statistical analysis title
    		 Visit 4: IncobotulinumtoxinA 25 Units Vs Placebo
    Statistical analysis description
    The difference in change of JRS severity subscore between treatment groups was analyzed by an ANCOVA according to a hierarchical test procedure. Second step of hierarchy is hypothesis of superiority of 25 unit dose group NT 201 compared to placebo. This was tested confirmatory (α=0.05, 2-sided) by an ANCOVA with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates based on LS means comparison. Missing values were imputed by LOCF.
    Comparison groups
    Double-blind MP: IncobotulinumtoxinA 25 Units v Double-blind MP: Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1452
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.2

    Secondary: Double-blind MP: Change from Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)

    		 Close Top of page
    End point title
    		 Double-blind MP: Change from Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)
    End point description
    BSDI is a scale for assessment of impairment of specific activities of daily living caused by blepharospasm. BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranging from 0 (=no impairment) to 4 (=no longer possible due to illness). The BSDI total score is a mean score for non-missing items ranging from 0 to 4. It is calculated by adding scores of all applicable and answered items, and dividing the resulting sum by the number of items answered. Outcome values represent LS mean differences between baseline and visit 4 (visit 4 value minus baseline value) resulting from ANCOVA with treatment group, pooled site, gender as fixed factors and baseline BSDI total score, age as covariates. Missings were replaced by the LOCF method. Negative values denote an improvement, while positive values denote deterioration vs. baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 43 (Visit 4)
    End point values
    		 Double-blind MP: Placebo Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Number of subjects analysed
    20 [4]
    22 [5]
    19 [6]
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.4 (-0.8 to 0.0)
    -0.5 (-0.9 to -0.2)
    -0.7 (-1.1 to -0.3)
    Notes
    [4] - FAS
    [5] - FAS
    [6] - FAS
    No statistical analyses for this end point

    Secondary: Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)

    		 Close Top of page
    End point title
    		 Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)
    End point description
    PEGR scale is a descriptive subjective 9-point response self-rating scale ranging from “complete abolishment of signs and symptoms” (value=+4) down to “very marked worsening” (value=-4). Outcome values represent least square means at visit 4 resulting from an ANCOVA with treatment group, pooled site, gender as fixed factors and age as covariates. Missing were set to a zero effect (value=0). Positive values denote an improvement, while negative values denote deterioration.
    End point type
    Secondary
    End point timeframe
    Baseline, Final Visit (Day 43-Day 141)
    End point values
    		 Double-blind MP: Placebo Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Number of subjects analysed
    20 [7]
    22 [8]
    19 [9]
    Units: score on a scale
        least squares mean (confidence interval 95%)
    1.3 (0.7 to 1.9)
    1.8 (1.2 to 2.4)
    2.2 (1.5 to 2.8)
    Notes
    [7] - FAS
    [8] - FAS
    [9] - FAS
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    Double-blind MP: Placebo
    Reporting group description
    		 Subjects received 1.0 mL placebo matched to incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular muscles on Day 1 in the double-blind MP.

    Reporting group title
    OLEX: IncobotulinumtoxinA 70 Units
    Reporting group description
    		 Subjects received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session (35 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the OLEX Period.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 25 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.

    Reporting group title
    Double-blind MP: IncobotulinumtoxinA 50 Units
    Reporting group description
    		 Subjects received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.

    Serious adverse events
    		 Double-blind MP: Placebo OLEX: IncobotulinumtoxinA 70 Units Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    2 / 22 (9.09%)
    1 / 19 (5.26%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4.5%
    Non-serious adverse events
    		 Double-blind MP: Placebo OLEX: IncobotulinumtoxinA 70 Units Double-blind MP: IncobotulinumtoxinA 25 Units Double-blind MP: IncobotulinumtoxinA 50 Units
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 20 (30.00%)
    4 / 39 (10.26%)
    7 / 22 (31.82%)
    7 / 19 (36.84%)
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injection site swelling
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Eyelid ptosis
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 39 (5.13%)
    2 / 22 (9.09%)
    3 / 19 (15.79%)
         occurrences all number
    0
    2
    2
    3
    Blepharospasm
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye irritation
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye pruritus
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Eye swelling
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eyelid disorder
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Eyelid function disorder
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blepharitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry eye
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 39 (5.13%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Periorbital oedema
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Gastritis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Hepatic steatosis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Rhinitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 39 (0.00%)
    0 / 22 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 39 (0.00%)
    1 / 22 (4.55%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Jul 2014
    1) Change in safety information: Due to the global harmonization of the Company Core Safety Information (CCSI) which is included as RSI within the investigator's brochure (IB) new safety information have been included for the indication blepharospasm. Common AEs related to NT 201 in the indication BEB were updated. 2) Updates in the current approval status and external responsibilities implemented.
    04 May 2015
    1) Addition of a new safety assessment to prospectively monitor suicidality in order to comply with FDA guidance on suicidality testing in all clinical trials investigating neurological indications: Columbia Suicide Severity Rating Scale (C-SSRS). 2) Addition of a new safety variable (classified as other safety variable) based on the results of the C-SSRS. 3) Addition of an exclusion criterion specifying that subjects with significant risk of suicidality at the baseline assessment were to be excluded. 4) Addition of a new eligibility criterion for injection in the OLEX period: no significant risk of suicidality since last injection based on the investigator's judgement, or if appropriate, as indicated of "no" to questions 4 or 5 in the suicidal ideation section of the C-SSRS, or no non suicidal self-injurious behavior, or no suicidal behavior. 5) Addition of a new discontinuation criterion: subjects were to be discontinued if there was a positive report on suicidality based on the C-SSRS. 6) Modification of data management procedures clarifying documentation of the C-SSRS results. 7) Modification of the definition of SAEs further specifying suicidal ideation (a response of “yes” to questions 4 or 5) or any suicidal behavior as “medically important condition”. 8) Description of the analysis of C-SSRS data. 9) New data added to the risk-benefit assessment.

    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 06 17:15:36 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA