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   42758   clinical trials with a EudraCT protocol, of which   7042   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) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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, long-term, follow-up study in Japan to evaluate the safety, tolerability, and efficacy of adjunctive treatment with oral L059 (levetiracetam) in epilepsy subjects with generalized tonic-clonic (GTC) seizures

    Summary
    EudraCT number
    2016-002879-96
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    19 Apr 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Oct 2016
    First version publication date
    15 Oct 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    N01361
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01398956
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Japan Co. Ltd.
    Sponsor organisation address
    8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, Japan, 160-0023
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, 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
    27 May 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Apr 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Provide the Levetiracetam (LEV) treatment to epilepsy subjects in Japan who are judged to benefit from continued treatment with LEV by the investigators and who are willing to continuously receive this drug. Evaluate the safety and tolerability of long-term administration of LEV at doses up to 60 mg/kg/day or 3000 mg/day in epilepsy subjects with generalized tonic-clonic seizures in Japan who have completed the N01159 or N01363 or have discontinued the N01159 due to lack of efficacy.
    Protection of trial subjects
    Not applicable
    Background therapy
    Antiepileptic drug(s)
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    30 Jun 2011
    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
    Japan: 44
    Worldwide total number of subjects
    44
    EEA total number of subjects
    0
    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)
    6
    Adolescents (12-17 years)
    8
    Adults (18-64 years)
    29
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study started to enroll subjects in Japan in June 2011.

    Pre-assignment
    Screening details
    Participant Flow refers to the Safety Set (SS) which consisted of all subjects who took at least one dose of study medication in this study.

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

    Arms
    Arm title
    Levetiracetam
    Arm description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study
    Arm type
    Experimental

    Investigational medicinal product name
    Keppra
    Investigational medicinal product code
    LEV tablet
    Other name
    Levetiracetam
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tables in 250 mg and 500 mg concentration

    Investigational medicinal product name
    E Keppra
    Investigational medicinal product code
    LEV syrup
    Other name
    Levetiracetam
    Pharmaceutical forms
    Granules for syrup
    Routes of administration
    Oral use
    Dosage and administration details
    Dry syrup 50%: 0.5 g Levetiracetam content in 1 g dry syrup

    Number of subjects in period 1
    Levetiracetam
    Started
    44
    Completed
    34
    Not completed
    10
         Withdrawal Criteria No.3
    1
         Subject moved a long distance
    1
         AE, non-serious non-fatal
    4
         Consent withdrawn by subject
    4

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Levetiracetam
    Reporting group description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study

    Reporting group values
    Levetiracetam Total
    Number of subjects
    44 44
    Age Categorical
    Units: Subjects
        >= 24 months - < 12 years
    6 6
        >= 12 - < 18 years
    8 8
        >=18 - < 65 years
    29 29
        >= 65 - < 85 years
    1 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    26.1 ± 13.9 -
    Gender Categorical
    Units: Subjects
        Male
    28 28
        Female
    16 16

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Levetiracetam
    Reporting group description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study

    Subject analysis set title
    Levetiracetam (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study

    Subject analysis set title
    Levetiracetam (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study

    Primary: Incidence of treatment emergent adverse events during the entire study period

    Close Top of page
    End point title
    Incidence of treatment emergent adverse events during the entire study period [1]
    End point description
    End point type
    Primary
    End point timeframe
    Evaluation and Withdrawal Periods
    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 endpoint. Results were summarized in tables as descriptive statistics only.
    End point values
    Levetiracetam (SS)
    Number of subjects analysed
    44
    Units: units on a scale
        Number of TEAEs
    626
    No statistical analyses for this end point

    Secondary: The percentage change in Generalized Tonic-Clonic (GTC) seizure frequency per week over the Evaluation Period from either of the Combined Baseline Periods of the previous studies (N01159 or N01363).

    Close Top of page
    End point title
    The percentage change in Generalized Tonic-Clonic (GTC) seizure frequency per week over the Evaluation Period from either of the Combined Baseline Periods of the previous studies (N01159 or N01363).
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline of feeder study until end of study
    End point values
    Levetiracetam (FAS)
    Number of subjects analysed
    43
    Units: units on a scale
    median (confidence interval 95%)
        percent change of combined baseline periods
    -92.07 (-97.16 to -64.64)
    No statistical analyses for this end point

    Secondary: The incidence of adverse drug reactions during the entire study period

    Close Top of page
    End point title
    The incidence of adverse drug reactions during the entire study period
    End point description
    Adverse drug reactions excludes Adverse Events (AEs) described by the investigators with no relationship to study drug.
    End point type
    Secondary
    End point timeframe
    Evaluation and Withdrawal Periods
    End point values
    Levetiracetam (SS)
    Number of subjects analysed
    44
    Units: units on a scale
        Number of ADRs
    46
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) were collected from Visit 1 (Week 0) until Safety Follow Up Visit.
    Adverse event reporting additional description
    Advers events refers to the Safety Set (SS) which consisted of all subjects who took at least one dose of study medication in this study.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Levetiracetam (SS)
    Reporting group description
    Levetiracetam dose will be adjusted at the investigator’s discretion in the range from 20mg/kg/day or 1000mg/day to 60mg/kg/day or 3000mg/day during this study

    Serious adverse events
    Levetiracetam (SS)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 44 (29.55%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Scoliosis surgery
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Medical observation
         subjects affected / exposed
    1 / 44 (2.27%)
         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)
    Breast adenoma
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Status asthmaticus
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Monoplegia
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Convulsion
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Torticollis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture malunion
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Levetiracetam (SS)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    41 / 44 (93.18%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    7 / 44 (15.91%)
         occurrences all number
    16
    Excoriation
         subjects affected / exposed
    6 / 44 (13.64%)
         occurrences all number
    32
    Wound
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    4
    Investigations
    Weight increased
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    6
    Electrocardiogram QT prolonged
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Protein urine present
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Cough
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    4
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    16 / 44 (36.36%)
         occurrences all number
    40
    Dizziness
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    4
    Headache
         subjects affected / exposed
    9 / 44 (20.45%)
         occurrences all number
    21
    Somnolence
         subjects affected / exposed
    10 / 44 (22.73%)
         occurrences all number
    10
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    8 / 44 (18.18%)
         occurrences all number
    14
    Gastrointestinal disorders
    Dental caries
         subjects affected / exposed
    11 / 44 (25.00%)
         occurrences all number
    13
    Diarrhoea
         subjects affected / exposed
    8 / 44 (18.18%)
         occurrences all number
    14
    Nausea
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    5
    Vomiting
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    7
    Constipation
         subjects affected / exposed
    7 / 44 (15.91%)
         occurrences all number
    8
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    6
    Skin erosion
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    12
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Pain in extremity
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    6
    Infections and infestations
    Influenza
         subjects affected / exposed
    9 / 44 (20.45%)
         occurrences all number
    12
    Nasopharyngitis
         subjects affected / exposed
    35 / 44 (79.55%)
         occurrences all number
    138
    Otitis media
         subjects affected / exposed
    6 / 44 (13.64%)
         occurrences all number
    6
    Bronchitis
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    5
    Conjunctivitis
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Gastroenteritis
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    11
    Pulpitis dental
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Feb 2012
    - Update to the list of restricted concomitant medications; piracetam and pregabalin were added to the list - Update to the section of rescue medication; fosphenytoin sodium hydrate (injection) was added to the section - Administrative changes
    29 Jan 2013
    - Update to the section of approval status in Japan and overseas; an approval in Dec 2011 by the Food and Drug Administration (FDA) for LEV as adjunctive treatment in children aged >=1 months was added - Update to the list of concomitant AEDs; stiripentol was added to the list - Update to the list of restricted concomitant medications; paliperidone was added to the list - Administrative changes - Corrections of typographical errors

    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 © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA