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   35474   clinical trials with a EudraCT protocol, of which   5826   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).
     
    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:
    AN OPEN-LABEL, MULTICENTER, MULTINATIONAL STUDY OF LACOSAMIDE AS FIRST ADD-ON ANTIEPILEPTIC DRUG (AED) TREATMENT IN SUBJECTS WITH PARTIAL-ONSET SEIZURES

    Summary
    EudraCT number
    2009-011181-28
    Trial protocol
    ES   AT   FI   IT   PL   NL   BG   FR   GR   HU   PT   DE   CZ   DK  
    Global end of trial date
    09 Aug 2013

    Results information
    Results version number
    v1(current)
    This version publication date
    28 Jun 2016
    First version publication date
    25 Jul 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    SP0954
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00955357
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB BIOSCIENCES, INC.
    Sponsor organisation address
    8010 Arco Corporate Drive, Raleigh, United States, 27617
    Public contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
    Scientific contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Sep 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Aug 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to evaluate the efficacy and safety of oral LCM as first add-on treatment in subjects with uncontrolled partial-onset seizures with or without secondary generalization after treatment with first adequate AED monotherapy regimen, compared to subjects with uncontrolled partial-onset seizures with or without secondary generalization despite prior adequate treatment with at least 2 AEDs (concurrently or sequentially).
    Protection of trial subjects
    None
    Background therapy
    Not applicable
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    05 Aug 2009
    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: 1
    Country: Number of subjects enrolled
    Bulgaria: 111
    Country: Number of subjects enrolled
    Czech Republic: 2
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Finland: 8
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Greece: 12
    Country: Number of subjects enrolled
    Italy: 33
    Country: Number of subjects enrolled
    Mexico: 102
    Country: Number of subjects enrolled
    Romania: 7
    Country: Number of subjects enrolled
    Russian Federation: 5
    Country: Number of subjects enrolled
    Spain: 55
    Country: Number of subjects enrolled
    Turkey: 12
    Country: Number of subjects enrolled
    United States: 104
    Worldwide total number of subjects
    456
    EEA total number of subjects
    233
    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)
    3
    Adults (18-64 years)
    439
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    An estimated 656 subjects were to be enrolled in the study at approximately 130 sites in the US, Europe, and the rest of the world.

    Pre-assignment
    Screening details
    Overall 461 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 456 subjects were included in the Safety Set.

    Period 1
    Period 1 title
    Study Overall (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    First Add-on
    Arm description
    Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
    Arm type
    Experimental

    Investigational medicinal product name
    Lacosamide
    Investigational medicinal product code
    Lacosamide LCM
    Other name
    Vimpat
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    First Add-on: Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Later Add-on: Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.

    Arm title
    Later Add-on
    Arm description
    Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
    Arm type
    Experimental

    Investigational medicinal product name
    Lacosamide
    Investigational medicinal product code
    Lacosamide LCM
    Other name
    Vimpat
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    First Add-on: Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Later Add-on: Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.

    Number of subjects in period 1
    First Add-on Later Add-on
    Started
    96
    360
    Completed
    68
    247
    Not completed
    28
    113
         Non-Fatal, Serious AE(s)
             -
             6
         Protocol deviation
             5
             13
         Other (Non compliance to study procedures)
             1
             -
         Lack of efficacy
             -
             6
         Non compliance to study procedures
             -
             1
         Consent withdrawn by subject
             7
             9
         Prohibited Antiepileptic Drug change
             -
             1
         SAE, non-fatal + AE, non-serious non-fatal
             2
             1
         Patient moving out of area
             -
             1
         Study medication not tolerated
             -
             1
         Non-Fatal, Non-Serious AE(s)
             9
             62
         Lost to follow-up
             3
             12
         Fatal, Serious AE(s)
             1
             -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    First Add-on
    Reporting group description
    Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Reporting group title
    Later Add-on
    Reporting group description
    Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Reporting group values
    First Add-on Later Add-on Total
    Number of subjects
    96 360 456
    Age Categorical
    Units: Subjects
        <=18 years
    4 7 11
        Between 18 and 65 years
    82 349 431
        >=65 years
    10 4 14
    Age Continuous
    Units: years
        median (full range (min-max))
    37.5 (18 to 82) 38 (16 to 74) -
    Gender Categorical
    Units: Subjects
        Female
    53 180 233
        Male
    43 180 223
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    11 6 17
        Asian
    0 12 12
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    1 19 20
        White
    79 278 357
        More than one race
    5 45 50
        Unknown or Not Reported
    0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    24 99 123
        Not Hispanic or Latino
    72 261 333
        Unknown or Not Reported
    0 0 0
    Weight
    Units: kilogram
        median (full range (min-max))
    71.8 (42 to 132.9) 73 (41.9 to 147.4) -
    BMI
    Units: kilogram per m^2
        median (full range (min-max))
    25.3 (14.5 to 42.5) 25.5 (17.3 to 53.9) -
    Height
    Units: centimeter
        median (full range (min-max))
    166.5 (149 to 186) 167.6 (140 to 197) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    First Add-on
    Reporting group description
    Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Reporting group title
    Later Add-on
    Reporting group description
    Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Primary: The proportion of subjects who achieved 'seizure-free status' during the first 12 weeks of the Maintenance Phase

    Close Top of page
    End point title
    The proportion of subjects who achieved 'seizure-free status' during the first 12 weeks of the Maintenance Phase [1]
    End point description
    A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
    End point type
    Primary
    End point timeframe
    From Week 7 (end of Week 6) to end of Week 18
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    First Add-on Later Add-on
    Number of subjects analysed
    72
    261
    Units: percentage of subjects
    number (not applicable)
        percentage of subjects
    37.5
    14.9
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment Emergent Adverse Events were collected from Screening (Week -1) until the end of the study ( up to Week 33).
    Adverse event reporting additional description
    Treatment Emergent Adverse Events started on/after the date of first dose and within 30 days of the date of last dose.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.1
    Reporting groups
    Reporting group title
    Later Add-on
    Reporting group description
    Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Reporting group title
    First Add-on
    Reporting group description
    Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week

    Serious adverse events
    Later Add-on First Add-on
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 360 (5.28%)
    8 / 96 (8.33%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    1 / 360 (0.28%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    2 / 360 (0.56%)
    2 / 96 (2.08%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 360 (0.56%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coordination abnormal
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures with secondary generalisation
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (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
    Pyrexia
         subjects affected / exposed
    2 / 360 (0.56%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Panic attack
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypochloraemia
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 360 (0.28%)
    0 / 96 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 360 (0.00%)
    1 / 96 (1.04%)
         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
    Later Add-on First Add-on
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    212 / 360 (58.89%)
    53 / 96 (55.21%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    119 / 360 (33.06%)
    30 / 96 (31.25%)
         occurrences all number
    159
    37
    Somnolence
         subjects affected / exposed
    54 / 360 (15.00%)
    6 / 96 (6.25%)
         occurrences all number
    65
    8
    Tremor
         subjects affected / exposed
    22 / 360 (6.11%)
    3 / 96 (3.13%)
         occurrences all number
    23
    3
    Headache
         subjects affected / exposed
    41 / 360 (11.39%)
    13 / 96 (13.54%)
         occurrences all number
    57
    19
    Eye disorders
    Vision blurred
         subjects affected / exposed
    24 / 360 (6.67%)
    2 / 96 (2.08%)
         occurrences all number
    28
    3
    Diplopia
         subjects affected / exposed
    17 / 360 (4.72%)
    7 / 96 (7.29%)
         occurrences all number
    17
    7
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    22 / 360 (6.11%)
    9 / 96 (9.38%)
         occurrences all number
    22
    11
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 360 (1.11%)
    6 / 96 (6.25%)
         occurrences all number
    4
    6
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    24 / 360 (6.67%)
    8 / 96 (8.33%)
         occurrences all number
    27
    8
    Infections and infestations
    Influenza
         subjects affected / exposed
    4 / 360 (1.11%)
    5 / 96 (5.21%)
         occurrences all number
    4
    5

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Oct 2009
    Protocol Amendment 1, dated 06 Oct 2009, provided the following key changes. Based on the date of the amendment, 8 subjects were enrolled globally at the time of the amendment. • The study was conducted only in countries in which LCM was commercially available at the time of study completion; therefore, reference to the fact that LCM was to be provided according to local laws where not commercially available was removed because it was no longer applicable • The liver function test (LFT) withdrawal criteria were revised to reflect the Sponsor’s current understanding of the safety profile of LCM based on a comprehensive review of the data from clinical studies • The AEs of special interest were revised to reflect the Sponsor’s current understanding of the potential risks of LCM based on a comprehensive review of the data from clinical studies and commitments to regulatory agencies • The approach to detect safety signals was clarified to reflect the Sponsor’s current practice • Other changes made in this amendment were minor or administrative
    09 Jul 2010
    Protocol Amendment 2, dated 09 Jul 2010, provided the following key changes. Based on the date of the amendment, 111 subjects were enrolled globally at the time of the amendment. • The inclusion criteria were revised to reflect the minimum age of eligible subjects in various countries and regions of the world. In addition, the inclusion criterion for newly diagnosed subjects in the First Add-On Group was updated to clarify that subjects were taking adequate monotherapy and to define what was considered adequate monotherapy for the purpose of this study. The maximum period for the time between the epilepsy diagnosis and the Screening Visit of the First Add-On Group was extended to 24 months in order to better reflect adjunctive therapy in clinical practice • Exclusion criteria were amended to exclude subjects with cranial surgery within the last year prior to the study. Cranial surgery indicated the presence of acute or unstable neurological disorders, which were exclusionary per protocol • Visit windows for titration phone calls were updated to allow for a variation in time of ±1 day relative to Visit 2 • Other changes made in this amendment were minor or administrative
    14 Dec 2010
    Protocol Amendment 3, dated 14 Dec 2010, was a substantial amendment and provided the following key changes. Based on the date of the amendment, 242 subjects were enrolled globally at the time of the amendment. • An exclusion criterion was added for known sodium channelopathy. The decision to exclude subjects with known channelopathies, such as Brugada syndrome, from clinical studies with LCM was based on a Food and Drug Administration (FDA) recommendation (17 Aug 2010). The basis for this recommendation was a theoretical concern that enhanced slow inactivation of sodium channels by LCM may have been proarrhythmic in subjects with sodium channelopathies • Revisions were made to withdrawal criteria and follow-up recommendations for abnormal LFTs based on the following: o Newly adopted FDA Guidance for Industry on drug-induced liver injury, which went into effect in Jul 2009, and a recommendation from the FDA to reinsert previously included wording regarding additional withdrawal criteria and follow-up recommendations for abnormal LFTs in LCM protocols o Although no new liver-related safety issues with LCM had been identified, LFT abnormal was added as a postmarketing adverse drug reaction in the LCM Company Core Data Sheet and the EU Summary of Product Characteristics; therefore, LCM protocols were amended to reflect this addition With these revisions, liver-related safety signals continued to be detected via protocol-directed monitoring and additional follow up in ongoing and future LCM clinical studies
    11 Jul 2011
    Protocol Amendment 4, dated 11 Jul 2011, was a substantial amendment and provided the following key changes. Based on the date of the amendment, 401 subjects were enrolled globally at the time of the amendment. The changes in Protocol Amendment 4 only affected subjects in the First Add-On Group because the Later Add-On Group’s enrollment was closed prior to the amendment’s approval in any of the countries. • The Sponsor’s name was changed to UCB BIOSCIENCES, INC. Specific Sponsor contact information was updated, and the US phone numbers for reporting serious adverse events (SAEs) were revised. The name and address of the study medication supplier was updated • Switzerland was added as a participating country, with the inclusion criterion being revised to reflect the minimum age of eligible subjects from this country • The inclusion criterion defining the minimum allowed seizure frequency was revised to ≥3 partial-onset seizures (IA, IB, or IC) at any time during the 3 months prior to the Screening Visit from ≥1 partial-onset seizure (IA, IB, or IC) per 28 days. This change did not reflect a change in the number of seizures required in the 3 months prior to Screening, just a change in the frequency per month
    11 Jul 2011
    • In addition, the inclusion criterion defining the amount of time that a subject had to be on a stable AED dose regimen and concurrent stable vagus nerve stimulation (VNS) prior to Screening was reduced from 28 days to 7 days to accommodate the First Add-On Group subjects who may have required more frequent AED dose changes in clinical practice than the Later Add-On Group subjects • In accordance with the FDA Draft Guidance for Industry on suicidality (Suicidality: Prospective assessment of occurrence in clinical trials), which went into effect on 29 Oct 2010, the Columbia-Suicide Severity Rating Scale ([C-SSRS] Columbia University Medical Center, 2008) was added to all ongoing and new interventional protocols in order to prospectively assess the occurrence of treatment-emergent suicidality in clinical studies of drug and biological products (FDA, Draft Guidance for Industry 2010) • A list of anticipated SAEs was included in this amendment in compliance with the FDA Guidance for Industry and Investigators on safety reporting requirements for studies conducted under an open Investigational New Drug Application (Safety reporting requirements for IND and BE/BA studies), which went into effect on 28 Mar 2011 (FDA, Guidance for Industry and Investigators, 2010) • Other changes made in this amendment were administrative in nature

    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.
    This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA