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   35554   clinical trials with a EudraCT protocol, of which   5841   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:
    A multi-center, double-blind, historical control, randomized conversion to monotherapy study with Keppra XR for treatment of partial onset seizures

    Summary
    EudraCT number
    2007-000897-21
    Trial protocol
    PL  
    Global end of trial date
    14 Sep 2009

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

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    N01280
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00419094
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Pharma, S.A.
    Sponsor organisation address
    Chemin du Foriest, Braine-l’ Alleud, Belgium, 1420
    Public contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.com
    Scientific contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.com
    Sponsor organisation name
    UCB, Inc.
    Sponsor organisation address
    1950 Lake Park Drive, Smyrna, United States, 30080
    Public contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.com
    Scientific contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 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
    06 Nov 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Sep 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the efficacy of Keppra extended release (XR) compared with a historical control, in the conversion to monotherapy treatment of partial onset seizures.
    Protection of trial subjects
    Not applicable
    Background therapy
    Standard antiepileptic drug (AED) therapy
    Evidence for comparator
    Other AEDs based on historical control
    Actual start date of recruitment
    06 Aug 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Mexico: 60
    Country: Number of subjects enrolled
    Poland: 67
    Country: Number of subjects enrolled
    Russian Federation: 64
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    228
    EEA total number of subjects
    67
    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)
    31
    Adults (18-64 years)
    194
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The Efficacy (EFF) population is defined as all subjects in the Intent-to-Treat (ITT) population who enter into the Previous Antiepileptic (AED) Discontinuation (D/C) Phase. The Per Protocol (PP) population consists of all subjects in the EFF population who have no important protocol deviations related to efficacy.

    Pre-assignment
    Screening details
    Subjects are to be randomized into treatment with either Keppra XR 2000 mg/day or Keppra XR 1000 mg/day in a 3:1 ratio. 303 subjects were screened/enrolled and 228 randomized.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Keppra XR 1000 mg/day
    Arm description
    1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily).
    Arm type
    Experimental

    Investigational medicinal product name
    Keppra XR
    Investigational medicinal product code
    Levetriacetam XR
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Keppra XR 1000 mg/day: administered as two Keppra XR tablets and two Placebo tablets once daily Keppra XR 2000 mg/day: administered as four Keppra XR tablets once daily

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching Placebo Tablet

    Arm title
    Keppra XR 2000 mg/day
    Arm description
    2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily).
    Arm type
    Experimental

    Investigational medicinal product name
    Keppra XR
    Investigational medicinal product code
    Levetriacetam XR
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Keppra XR 1000 mg/day: administered as two Keppra XR tablets and two Placebo tablets once daily Keppra XR 2000 mg/day: administered as four Keppra XR tablets once daily

    Number of subjects in period 1
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day
    Started
    57
    171
    Completed
    50
    141
    Not completed
    7
    30
         Protocol deviation
    1
    14
         No contact for extended period
    -
    1
         Patient non-compliant
    -
    1
         Lack of efficacy
    1
    -
         SAE, non-fatal
    1
    1
         Error determining exit criteria
    1
    -
         AE, non-serious non-fatal
    2
    6
         Consent withdrawn by subject
    1
    5
         Lost to follow-up
    -
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Keppra XR 1000 mg/day
    Reporting group description
    1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily).

    Reporting group title
    Keppra XR 2000 mg/day
    Reporting group description
    2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily).

    Reporting group values
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day Total
    Number of subjects
    57 171 228
    Age Categorical
    Units: Subjects
        <=18 years
    11 31 42
        Between 18 and 65 years
    43 140 183
        >=65 years
    3 0 3
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    33.48 ± 16.32 34.31 ± 13.69 -
    Gender Categorical
    Units: Subjects
        Female
    33 99 132
        Male
    24 72 96
    Region of Enrollment
    Units: Subjects
        United States
    8 29 37
        Mexico
    17 43 60
        Poland
    16 51 67
        Russian Federation
    16 48 64

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Keppra XR 1000 mg/day
    Reporting group description
    1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily).

    Reporting group title
    Keppra XR 2000 mg/day
    Reporting group description
    2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily).

    Primary: The cumulative exit rate at 112 days after the beginning of the previous antiepileptic drug (AED) tapering phase

    Close Top of page
    End point title
    The cumulative exit rate at 112 days after the beginning of the previous antiepileptic drug (AED) tapering phase [1]
    End point description
    Cumulative exit rate at day 112, based on the duration between start date of previous AED tapering to the earliest date exit criterion was met; calculated using Kaplan Meier Methods. Subjects prematurely discontinued for reasons unrelated to exit criteria were censored as of last dose of study drug. Subjects who completed without meeting exit criteria were censored at Day 112. Exit criteria include increase in seizure frequency, severity, duration, status epilepticus, or new generalized seizure. Upper 95% 2-sided confidence limit for exit rate is compared to the historical control rate: 0.678.
    End point type
    Primary
    End point timeframe
    112 days
    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: Due to system limitations with studies using an external control, the stat. analysis results could not be entered in this section. The stat. analysis for the prim. and sec. efficacy variable was based on a comparison btw the historical control exit rate (0.678) to the upper limit of the 2-sided 95 % CI for the estimated event rate. If the upper limit of the 95 % CI for the estimate of the event rate for the Keppra arm was less than 0.678, the analysis was positive in favor of the Keppra arm.
    End point values
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day
    Number of subjects analysed
    0 [2]
    158
    Units: proportion of subjects
    number (confidence interval 95%)
        number (95% confidence interval)
    ( to )
    0.375 (0.297 to 0.453)
    Notes
    [2] - Primary Efficacy analysis was conducted for the Keppra XR 2000 mg/day group only.
    No statistical analyses for this end point

    Secondary: The cumulative rate of exit events, which include discontinuation due to exit criteria, withdrawal due to adverse events (AE) and withdrawal due to lack of efficacy, at 112 days after the beginning of previous antiepileptic drug (AED) tapering phase

    Close Top of page
    End point title
    The cumulative rate of exit events, which include discontinuation due to exit criteria, withdrawal due to adverse events (AE) and withdrawal due to lack of efficacy, at 112 days after the beginning of previous antiepileptic drug (AED) tapering phase
    End point description
    The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who prematurely discontinued for reasons unrelated to exit criteria, adverse event, or lack of efficacy were censored as of the last dose of study medication. Subjects who completed the study without having an exit event were censored as of Day 112.
    End point type
    Secondary
    End point timeframe
    112 days
    End point values
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day
    Number of subjects analysed
    0 [3]
    158
    Units: proportion of subjects
    number (confidence interval 95%)
        number (95% confidence interval)
    ( to )
    0.385 (0.307 to 0.463)
    Notes
    [3] - Evaluated for Keppra XR 2000 mg/day only.
    No statistical analyses for this end point

    Secondary: The cumulative rate of exit events due to any reasons at 112 days after the beginning of previous antiepileptic drug (AED) tapering phase

    Close Top of page
    End point title
    The cumulative rate of exit events due to any reasons at 112 days after the beginning of previous antiepileptic drug (AED) tapering phase
    End point description
    The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who completed the study without having an exit event were censored as of Day 112.
    End point type
    Secondary
    End point timeframe
    112 days
    End point values
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day
    Number of subjects analysed
    0 [4]
    158
    Units: proportion of subjects
    number (confidence interval 95%)
        number (95% confidence interval)
    ( to )
    0.475 (0.397 to 0.553)
    Notes
    [4] - Evaluated for Keppra XR 2000 mg/day only.
    No statistical analyses for this end point

    Secondary: The Cumulative Exit Rate at 112 days for the Keppra XR 1000 mg group After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase

    Close Top of page
    End point title
    The Cumulative Exit Rate at 112 days for the Keppra XR 1000 mg group After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase
    End point description
    Keppra XR 1000 mg arm was not intended for inferential analysis (planned 3 to 1 randomization, Keppra XR 2000 mg: 1000 mg). The Exit Rate was based on the duration between the start date of previous AED tapering to the earliest date an exit crterion was met. Subjects who prematurely discontinued for reasons unrelated to exit criteria were censored as of the last dose of study medication. Subjects who completed the study without meeting an exit criterion were censored as of Day 112.
    End point type
    Secondary
    End point timeframe
    112 days
    End point values
    Keppra XR 1000 mg/day Keppra XR 2000 mg/day
    Number of subjects analysed
    54
    0 [5]
    Units: proportion of subjects
    number (confidence interval 95%)
        number (95% confidence interval)
    0.334 (0.204 to 0.465)
    ( to )
    Notes
    [5] - Evaluated for Keppra XR 1000 mg/day only.
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 29 weeks
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    Keppra XR 2000 mg/day
    Reporting group description
    2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)

    Reporting group title
    Keppra XR 1000 mg/day
    Reporting group description
    1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)

    Serious adverse events
    Keppra XR 2000 mg/day Keppra XR 1000 mg/day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 171 (7.02%)
    2 / 57 (3.51%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    thrombosis
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ankle fracture
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    convulsion
         subjects affected / exposed
    4 / 171 (2.34%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    status epilepticus
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    acute psychosis
         subjects affected / exposed
    0 / 171 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis acute
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    back pain
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intervertebral disc protrusion
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lumbar spinal stenosis
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (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
    pulmonary tuberculosis
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyelonephritis
         subjects affected / exposed
    1 / 171 (0.58%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Keppra XR 2000 mg/day Keppra XR 1000 mg/day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    87 / 171 (50.88%)
    33 / 57 (57.89%)
    Nervous system disorders
    somnolence
         subjects affected / exposed
    38 / 171 (22.22%)
    12 / 57 (21.05%)
         occurrences all number
    40
    13
    headache
         subjects affected / exposed
    32 / 171 (18.71%)
    13 / 57 (22.81%)
         occurrences all number
    55
    34
    dizziness
         subjects affected / exposed
    15 / 171 (8.77%)
    3 / 57 (5.26%)
         occurrences all number
    19
    4
    convulsion
         subjects affected / exposed
    20 / 171 (11.70%)
    9 / 57 (15.79%)
         occurrences all number
    20
    9
    General disorders and administration site conditions
    irritablility
         subjects affected / exposed
    12 / 171 (7.02%)
    3 / 57 (5.26%)
         occurrences all number
    12
    3
    Ear and labyrinth disorders
    vertigo
         subjects affected / exposed
    7 / 171 (4.09%)
    3 / 57 (5.26%)
         occurrences all number
    7
    3
    Gastrointestinal disorders
    abdominal pain
         subjects affected / exposed
    6 / 171 (3.51%)
    3 / 57 (5.26%)
         occurrences all number
    6
    3
    Infections and infestations
    nasopharyngitis
         subjects affected / exposed
    7 / 171 (4.09%)
    3 / 57 (5.26%)
         occurrences all number
    7
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Apr 2007
    Protocol Amendment 1 (dated 04 Apr 2007) provided for administrative changes, Content changes, and changes to the study design. This amendment was implemented before any subjects were screened for the study. • The content changes tightened the inclusion/exclusion criteria and were reflective of the criteria indicated in the historical control White Paper or Alternative Monotherapy Design in the Treatment of Epilepsy • The inclusion criterion regarding baseline AED use was modified to 'If taking 2 AEDs, 1 of the baseline AEDs should be taken at less than or equal to 50% of the minimum recommended dose.' • The exclusion criteria were modified as follows: • New criterion added: Seizures that are uncountable due to clustering during the 8-week period prior to Screening (Visit 1) and during the 8-week Baseline Period
    04 Apr 2007
    • Benzodiazepine use. (Original text: Regular use of benzodiazepines or intake of benzodiazepines on more than an occasional basis [more than average once per week]) • Use of an investigational drug or device in the 4 months preceding randomization • A sensitivity analysis was added to satisfy anticipated requirements from FDA • Additionally, changes were made to the study design. Rather than utilizing a randomization ratio of 1:1, a ratio of 3:1 was used. This changed the planned sample size to 223 subjects (167 in the 2000 mg/day group and 56 in the 1000 mg/day group). The anticipated number of subjects to be screened was changed to 279. For the statistical analysis, only the 2000 mg/day group was planned to be tested against the historical control. The dose of 2000 mg/day was 90% powered
    14 Apr 2008
    Protocol Amendment 2 (dated 14 Apr 2008) provided administrative changes, changes to the Inclusion and Exclusion Criteria section, and changes to the Permitted Concomitant Treatments section due to specific wording inadvertently omitted or documented incorrectly on the previous protocol amendment. This amendment was implemented after 64 subjects had been screened for participation in the study. The change to the inclusion criteria was a modification of the amount of baseline AEDs allowed. Amendment 2 allowed 1 of the baseline AEDs to have been taken at less than or equal to 50% of the minimum recommended dose. The wording for the administration of concomitant antiepileptic medications allowed for tapering off to start at Visit 4 because the visit number was incorrectly documented in original protocol. The CRF page entitled “Subject Eligibility (Inclusion Criteria)” was amended to include additional language noted in this amendment.

    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

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/22516508
    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