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    Clinical Trial Results:
    An Open-Label Study to Determine Safety, Tolerability, and Efficacy of Long-Term Oral Lacosamide as Adjunctive Therapy in Children With Epilepsy

    Summary
    EudraCT number
    2011-001559-35
    Trial protocol
    BE   DE   HU   IT   Outside EU/EEA   PL   FR  
    Global end of trial date
    18 May 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    03 Dec 2021
    First version publication date
    03 Dec 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    SP848
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00938912
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB BIOSCIENCES, Inc.
    Sponsor organisation address
    8010 Arco Corporate Drive, Raleigh, United States, NC 27617
    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)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000402-PIP03-17
    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
    21 Jul 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 May 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    18 May 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To obtain information about the safety, tolerability, and pharmacokinetics (PK) of lacosamide (LCM) during long-term exposure • To obtain preliminary efficacy data on seizure frequency during long term exposure
    Protection of trial subjects
    All participants were closely monitored during the conduct of the study. Microvettes to minimize blood volume in lab draws and topical analgesics were encouraged for needle sticks. Permitted opportunistic blood draws (piggyback study blood collection on health required blood draws).
    Background therapy
    Background therapy with anti-seizure medication (ASM) as permitted in the protocol and vagus nerve stimulation (VNS) permitted.
    Evidence for comparator
    Not applicable.
    Actual start date of recruitment
    09 Dec 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    10 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    China: 61
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 44
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Japan: 46
    Country: Number of subjects enrolled
    Mexico: 22
    Country: Number of subjects enrolled
    Poland: 22
    Country: Number of subjects enrolled
    Ukraine: 42
    Country: Number of subjects enrolled
    United States: 112
    Worldwide total number of subjects
    365
    EEA total number of subjects
    82
    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)
    21
    Children (2-11 years)
    229
    Adolescents (12-17 years)
    114
    Adults (18-64 years)
    1
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study started to enroll study participants in December 2009 and concluded in May 2021. Eligible study participants were allowed to roll over from study SP0847 (NCT00938431), SP0966 (NCT01969851) and EP0060 (NCT02710890) and eligible study participants were also allowed to directly enroll into the study.

    Pre-assignment
    Screening details
    Total 366 participants were enrolled. Among 366, 365 participants received treatment. One participant was enrolled, but did not receive treatment prior to discontinuing due to ineligibility.

    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
    Lacosamide (All Participants)
    Arm description
    Participants aged greater than or equal to (≥1) month received either lacosamide (LCM) 2-12 milligrams/kilograms/day (mg/kg/day) (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years.
    Arm type
    Experimental

    Investigational medicinal product name
    Lacosamide
    Investigational medicinal product code
    Other name
    LCM
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants aged ≥1 month received either LCM 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 600 mg/day based on body weight, whichever was lower) for approximately 2 years at prespecified time points.

    Investigational medicinal product name
    Lacosamide
    Investigational medicinal product code
    Other name
    LCM
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day based on body weight, whichever was lower) for approximately 2 years at prespecified time points.

    Number of subjects in period 1
    Lacosamide (All Participants)
    Started
    365
    Completed
    254
    Not completed
    111
         Participant was scheduled for lobal resection
    1
         No longer wished to participate in the study
    1
         Protocol Deviation
    2
         Participant had a creatinine clearance <30 mL/min
    1
         Participant self adjusted antiepileptic medication
    1
         Consent withdrawn by subject
    28
         Participant moved to another city
    1
         Adverse event, non-fatal
    24
         Adverse event, fatal
    1
         Did not meet Eligibility criteria
    1
         Participant relocated not related to AE
    1
         Participant experienced break through seizures
    1
         Lost to follow-up
    4
         Lack of efficacy
    43
         Participant needed prohibit medication
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lacosamide (All Participants)
    Reporting group description
    Participants aged greater than or equal to (≥1) month received either lacosamide (LCM) 2-12 milligrams/kilograms/day (mg/kg/day) (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years.

    Reporting group values
    Lacosamide (All Participants) Total
    Number of subjects
    365 365
    Age Categorical
    Units: participants
        <=18 years
    365 365
        Between 18 and 65 years
    0 0
        >=65 years
    0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    9.28 ( 4.55 ) -
    Sex: Female, Male
    Units: participants
        Female
    173 173
        Male
    192 192

    End points

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    End points reporting groups
    Reporting group title
    Lacosamide (All Participants)
    Reporting group description
    Participants aged greater than or equal to (≥1) month received either lacosamide (LCM) 2-12 milligrams/kilograms/day (mg/kg/day) (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years.

    Subject analysis set title
    Lacosamide (All Participants) (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the Safety Set (SS) which included all enrolled study participants who took at least 1 dose of LCM in this study.

    Subject analysis set title
    Lacosamide (All Participants) (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the Full Analysis Set (FAS) which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.

    Primary: Number of Participants With At least One Treatment-Emergent Adverse Event (TEAE)

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    End point title
    Number of Participants With At least One Treatment-Emergent Adverse Event (TEAE) [1]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration. The Safety Set (SS) consisted of all enrolled study participants who took at least 1 dose of LCM in this study.
    End point type
    Primary
    End point timeframe
    From Baseline to End of Safety Follow-Up (up to 4.3 years)
    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
    Lacosamide (All Participants) (SS)
    Number of subjects analysed
    365
    Units: participants
    336
    No statistical analyses for this end point

    Primary: Number of Participants With Serious Adverse Events (SAEs)

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    End point title
    Number of Participants With Serious Adverse Events (SAEs) [2]
    End point description
    SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in participant hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment with parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above. The SS consisted of all enrolled study participants who took at least 1 dose of LCM in this study.
    End point type
    Primary
    End point timeframe
    From Baseline to End of Safety Follow-Up (up to 4.3 years)
    Notes
    [2] - 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
    Lacosamide (All Participants) (SS)
    Number of subjects analysed
    365
    Units: participants
    82
    No statistical analyses for this end point

    Primary: Number of participants that withdraw due to a Treatment-Emergent Adverse Event

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    End point title
    Number of participants that withdraw due to a Treatment-Emergent Adverse Event [3]
    End point description
    TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration. The SS consisted of all enrolled study participants who took at least 1 dose of LCM in this study.
    End point type
    Primary
    End point timeframe
    From Baseline to End of Safety Follow-Up (up to 4.3 years)
    Notes
    [3] - 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
    Lacosamide (All Participants) (SS)
    Number of subjects analysed
    365
    Units: participants
    27
    No statistical analyses for this end point

    Secondary: Percent change from Baseline in 28 Day partial-onset seizure frequency to the end of the Treatment Period

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    End point title
    Percent change from Baseline in 28 Day partial-onset seizure frequency to the end of the Treatment Period
    End point description
    Percent change in seizure frequency per 28 days (PCH) from Baseline value (B) to Treatment Period interval (T) was defined as:PCH =[(SFT– SFB)/SFB] x 100 where, SFT denoted seizure frequency during Treatment Period for relative interval in open-label study and SFB denoted baseline seizure frequency. For both periods, frequency was standardized to number of seizures per 28 days. For rollover participants, Baseline value from previous studies were designated as Baseline values in SP848. Baseline value for seizure counts for directly enrolled participants were taken from historical seizure count case report form (CRF)/electronic CRF (CRF/eCRF) module in combination with seizure diary data collected from date of Screening Visit to day prior to date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. Analysis set was FAS. Number of participants analyzed: participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline to End of Treatment Period (up to 4.2 years)
    End point values
    Lacosamide (All Participants) (FAS)
    Number of subjects analysed
    308
    Units: percent change
        arithmetic mean (standard deviation)
    -24.13 ( 112.08 )
    No statistical analyses for this end point

    Secondary: Percentage of participants With ≥50% reduction in 28-day partial-onset seizure frequency

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    End point title
    Percentage of participants With ≥50% reduction in 28-day partial-onset seizure frequency
    End point description
    A 50% responder is a participant experiencing a ≥50% reduction in partial-onset seizure frequency per 28 days from Baseline to end of specified time interval, else it is non-responder. For rollover participants, Baseline values from previous pediatric studies were designated as Baseline values in SP848. Baseline value for seizure counts for directly enrolled participants were taken from historical seizure count CRF/eCRF module in combination with seizure diary data collected from date of Screening Visit to day prior to date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. FAS consisted of all participants in the SS who had at least 1 completed post-Baseline seizure diary. Number of participants analyzed included those participants who were evaluable for assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline to End of Treatment Period (up to 4.2 years)
    End point values
    Lacosamide (All Participants) (FAS)
    Number of subjects analysed
    308
    Units: percentage of participants
        number (not applicable)
    53.6
    No statistical analyses for this end point

    Secondary: Percentage of participants With ≥75% reduction in 28-day partial-onset seizure frequency

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    End point title
    Percentage of participants With ≥75% reduction in 28-day partial-onset seizure frequency
    End point description
    A 75% responder is a participant experiencing a ≥75% reduction in partial-onset seizure frequency per 28 days from Baseline to end of specified time interval, else it is non-responder. For rollover participants, Baseline values from previous pediatric studies were designated as Baseline values in SP848. Baseline value for seizure counts for directly enrolled participants were taken from historical seizure count CRF/eCRF module in combination with seizure diary data collected from date of Screening Visit to day prior to date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. FAS consisted of all participants in the SS who had at least 1 completed post-Baseline seizure diary. Number of participants analyzed included those participants who were evaluable for assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline to End of Treatment Period (up to 4.2 years)
    End point values
    Lacosamide (All Participants) (FAS)
    Number of subjects analysed
    308
    Units: percentage of participants
        number (not applicable)
    40.3
    No statistical analyses for this end point

    Secondary: Number of seizure days per 28 days for participants with generalized seizures

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    End point title
    Number of seizure days per 28 days for participants with generalized seizures
    End point description
    A seizure day was defined as a day where any type of seizure was reported in the seizure diary and seizures were assessed. Days in the seizure diary which were marked as “not done” on the CRF/eCRF were not counted as seizure-free days. The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment and number analyzed (n) included those participants who were evaluable at specified time points only.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96
    End point values
    Lacosamide (All Participants) (FAS)
    Number of subjects analysed
    47
    Units: seizure days per 28 days
    arithmetic mean (standard deviation)
        Week 4 (n=47)
    14.59 ( 11.94 )
        Week 8 (n=46)
    14.83 ( 12.24 )
        Week 12 (n=46)
    13.68 ( 12.62 )
        Week 20 (n=46)
    12.57 ( 12.58 )
        Week 28 (n=43)
    13.10 ( 12.63 )
        Week 36 (n=43)
    11.43 ( 11.93 )
        Week 44 (n=40)
    9.24 ( 11.23 )
        Week 52 (n=41)
    10.48 ( 11.68 )
        Week 60 (n=39)
    10.31 ( 11.84 )
        Week 72 (n=39)
    11.15 ( 12.10 )
        Week 84 (n=38)
    11.87 ( 12.45 )
        Week 96 (n=37)
    10.73 ( 11.77 )
    No statistical analyses for this end point

    Secondary: Percentage of participants who achieved a seizure-free status

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    End point title
    Percentage of participants who achieved a seizure-free status
    End point description
    Study participants were considered seizure-free for a given period if they completed the period, reported zero seizures during the period, and had no more than 10% of days in the period for which seizure data were not available (ie, “not done” was noted on the Seizure Frequency CRF/eCRF module). The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline to End of Treatment Period (up to 4.2 years)
    End point values
    Lacosamide (All Participants) (FAS)
    Number of subjects analysed
    323
    Units: percentage of participants
        number (not applicable)
    7.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline to End of Safety Follow-Up (up to 4.3 years)
    Adverse event reporting additional description
    TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Lacosamide (All Participants) (SS)
    Reporting group description
    Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the SS which included all enrolled study participants who took at least 1 dose of LCM in this study.

    Serious adverse events
    Lacosamide (All Participants) (SS)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    82 / 365 (22.47%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Astrocytoma, low grade
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 365 (1.10%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Adverse drug reaction
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    Affective disorder
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Agitation
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucination, auditory
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nightmare
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sleep disorder
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Substance-induced psychotic disorder
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Endotracheal intubation complication
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Foreign body aspiration
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cyanosis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    21 / 365 (5.75%)
         occurrences causally related to treatment / all
    4 / 29
         deaths causally related to treatment / all
    0 / 0
    Status epilepticus
         subjects affected / exposed
    11 / 365 (3.01%)
         occurrences causally related to treatment / all
    2 / 16
         deaths causally related to treatment / all
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    5 / 365 (1.37%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    6 / 365 (1.64%)
         occurrences causally related to treatment / all
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    Partial seizures with secondary generalisation
         subjects affected / exposed
    4 / 365 (1.10%)
         occurrences causally related to treatment / all
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    Seizure cluster
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Partial seizures
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Headache
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Altered state of consciousness
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Clonic convulsion
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neurotoxicity
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lethargy
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychomotor skills impaired
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Simple partial seizures
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    8 / 365 (2.19%)
         occurrences causally related to treatment / all
    3 / 19
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haematemesis
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intussusception
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Traumatic tooth displacement
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Atlantoaxial instability
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    6 / 365 (1.64%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 365 (1.10%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 365 (0.82%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Tonsillitis
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Erythema infectiosum
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection fungal
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    4 / 365 (1.10%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Decreased appetite
         subjects affected / exposed
    2 / 365 (0.55%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperammonaemia
         subjects affected / exposed
    1 / 365 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 365 (0.27%)
         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
    Lacosamide (All Participants) (SS)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    291 / 365 (79.73%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    25 / 365 (6.85%)
         occurrences all number
    55
    Nervous system disorders
    Headache
         subjects affected / exposed
    45 / 365 (12.33%)
         occurrences all number
    97
    Somnolence
         subjects affected / exposed
    74 / 365 (20.27%)
         occurrences all number
    100
    Dizziness
         subjects affected / exposed
    69 / 365 (18.90%)
         occurrences all number
    114
    Tremor
         subjects affected / exposed
    21 / 365 (5.75%)
         occurrences all number
    23
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    80 / 365 (21.92%)
         occurrences all number
    126
    Fatigue
         subjects affected / exposed
    21 / 365 (5.75%)
         occurrences all number
    31
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    77 / 365 (21.10%)
         occurrences all number
    149
    Diarrhoea
         subjects affected / exposed
    40 / 365 (10.96%)
         occurrences all number
    52
    Abdominal pain
         subjects affected / exposed
    21 / 365 (5.75%)
         occurrences all number
    32
    Nausea
         subjects affected / exposed
    25 / 365 (6.85%)
         occurrences all number
    35
    Constipation
         subjects affected / exposed
    25 / 365 (6.85%)
         occurrences all number
    34
    Abdominal pain upper
         subjects affected / exposed
    19 / 365 (5.21%)
         occurrences all number
    29
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    36 / 365 (9.86%)
         occurrences all number
    43
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    91 / 365 (24.93%)
         occurrences all number
    253
    Upper respiratory tract infection
         subjects affected / exposed
    86 / 365 (23.56%)
         occurrences all number
    167
    Pharyngitis
         subjects affected / exposed
    37 / 365 (10.14%)
         occurrences all number
    48
    Gastroenteritis
         subjects affected / exposed
    29 / 365 (7.95%)
         occurrences all number
    35
    Influenza
         subjects affected / exposed
    29 / 365 (7.95%)
         occurrences all number
    38
    Viral infection
         subjects affected / exposed
    21 / 365 (5.75%)
         occurrences all number
    36
    Bronchitis
         subjects affected / exposed
    26 / 365 (7.12%)
         occurrences all number
    40
    Sinusitis
         subjects affected / exposed
    20 / 365 (5.48%)
         occurrences all number
    29
    Urinary tract infection
         subjects affected / exposed
    20 / 365 (5.48%)
         occurrences all number
    24
    Ear infection
         subjects affected / exposed
    19 / 365 (5.21%)
         occurrences all number
    27
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    26 / 365 (7.12%)
         occurrences all number
    28

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Nov 2009
    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 trials and commitments to regulatory agencies. 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 trials.
    13 Dec 2010
    Based on the analysis of SP847 Cohort 1 (study participants aged 5 to 11 years) safety and PK data, the maximum permitted LCM dose in SP848 was 12mg/kg/day (for study participants weighing up to 50kg) or 600mg/day (for study participants weighing >50kg). The decision to re-insert additional withdrawal criteria and follow-up recommendations for abnormal LFTs was based on the following: 1. Newly adopted FDA Guidance on Drug-Induced Liver Injury (July 2009) and a recommendation from the FDA to re-insert previously included wording regarding additional withdrawal criteria and follow-up recommendations for abnormal LFTs in LCM protocols. 2. Although no new liver-related safety issues with LCM had been identified, LFT abnormal had been 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. In addition, the protocol was revised to allow enrollment of study participants who had participated in other future LCM pediatric clinical studies in epilepsy (ie, in addition to SP847) to provide the opportunity to continue receiving LCM treatment in SP848.
    29 Jul 2011
    The sponsor’s name was changed from SCHWARZ to UCB BIOSCIENCES, INC. Specific sponsor contact information was updated. As recommended by FDA, text was added or modified to make it clear that maximum permitted LCM dose in SP848 was 12mg/kg/day or 600mg/day, whichever was lower. As recommended by FDA, Columbia-Suicide Severity Rating Scale (C-SSRS) was added to evaluate and identify study participants at risk for suicide while participating in a clinical study of a drug with CNS activity. Oral solution formulation of LCM used in this study was revised to contain 10mg/mL of drug substance (formerly containing 15mg/mL of drug substance). UCB, in agreement with the Committee for Medicinal Products for Human Use, initiated the recall of VIMPAT syrup 15mg/mL due to a quality defect related to the formation of a flake-like precipitate of LCM in the syrup. UCB received approval for a 10mg/mL syrup; thus, all study participants in study were transitioned to LCM 10mg/mL. Also, UCB did not receive any reports from investigative sites of the appearance of these flake-like precipitants in the clinical trial supplies of LCM 15mg/mL syrup formulation used in SP848. All study participants were required to have a 12-lead ECG conducted at LCM maximum plasma concentration (Cmax) 1 week after an initial LCM dose increase. This ECG could have been conducted at an unscheduled visit, if necessary. These participants were required to arrive at the clinic prior to taking their morning dose of LCM. Participants were administered their morning LCM dose by study personnel at the clinic so that an ECG (2 interpretable recordings approximately 20 to 30 minutes apart prior to vital signs assessment) could be performed 30 minutes to 1 hour after administration of LCM (ie, at LCM steady state Cmax). A list of SAEs was included in this amendment in compliance with recent US FDA guidance on safety reporting requirements for studies conducted under an open Investigational New Drug Application.
    09 Apr 2012
    Selected sites were permitted to directly enroll in SP848 up to approximately 100 eligible pediatric study participants ≥4 to ≤17 years of age with POS (deemed appropriate for treatment with adjunctive LCM) who had not previously participated in a LCM clinical study. The purpose of enrolling these study participants directly into SP848 was to obtain sufficient long-term safety exposures in the age range of ≥4 to ≤17 years of age; the additional long-term safety data were to be included in planned regulatory submissions for LCM as adjunctive therapy for POS in pediatric study participants aged 4 years and above with epilepsy. Based on regulatory agency recommendations to include scales to measure development and cognition, the Achenbach Child Behavior Checklist (CBCL); Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley®-III); and Tanner Scale were selected by UCB and added as assessments in SP848. In addition, a LCM palatability and ease of use questionnaire was added to the study assessments.
    22 Jan 2013
    In the FDA Division of Neurology Products’ 06 Aug 2012 Request for Information regarding SP847 Protocol Amendment 5, the Agency recommended that UCB revise an inclusion criterion to require the use of more than 1 AED as monotherapy before initiating adjunctive LCM therapy in SP847. UCB made this recommended change in the SP847 protocol (Amendment 6). In alignment with SP847, Inclusion Criterion 7 was modified to require that each study participant in SP848 have had uncontrolled POS after an adequate course of treatment (in the opinion of the investigator) with at least 2 AEDs (concurrently or sequentially). Inclusion Criterion 7 applied only to study participants who enrolled directly into SP848 without previous participation in a LCM clinical study. The Behavior Rating Inventory of Executive Function® (BRIEF®)/Behavior Rating Inventory of Executive Function®-Preschool Version (BRIEF®-P), Pediatric Quality of Life Inventory (PedsQL™), and health care resource use were added as assessments in SP848.
    16 Nov 2016
    The primary purpose of this protocol amendment was to permit enrollment of up to approximately 75 eligible pediatric study participants ≥4 to <17 years of age with POS (deemed appropriate for treatment with LCM) who had previously participated in the iv LCM clinical study EP0060. The purpose of enrolling these study participants was to obtain additional long-term safety exposures in the age range of ≥4 to <17 years of age; the additional long-term safety data were submitted on 30 Apr 2020 and 15 May 2020 to the LCM iv and tablet New Drug Applications, respectively. Of note, EP0060 was further amended (Protocol Amendment 3; 30 Apr 2018) to allow enrollment of up to 100 study participants ≥1 month to <17 years of age, all of whom could rollover into SP848. Sponsor language for monitoring of PDILI events was added to increase clarity for the sites and to align across programs. Addition of this language was to align with FDA guidance regarding monitoring of PDILI events and did not reflect a change in the liver safety signal for LCM. In addition, Exclusion Criterion 16, which excluded use of vigabatrin or felbamate, was removed.
    06 Feb 2017
    This administrative amendment fixed the numbering of the exclusion criteria that resulted from the removal of Exclusion Criterion 16 in Protocol Amendment 6.
    20 Oct 2020
    The primary purpose of this protocol amendment was to align with modifications made to the Paediatric Investigation Plan. Changes included: • A new categorization for main primary and secondary endpoints key binding element was proposed to ensure reporting compliance with registries (European Union Drug Regulating Authorities Clinical Trials Database, clinicaltrials.gov). This categorization did not affect the type or processing of data collected and reported in the study report, which were assessed as initially planned. • Further clarification was provided for the study duration as well as the wording and categorization of the primary, secondary, and other variables. In addition, language specifying applicable study conduct modifications due to the coronavirus disease 2019 (COVID-19) pandemic was added.

    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
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    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.

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