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   35519   clinical trials with a EudraCT protocol, of which   5839   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An open-label, multi-center, follow-up trial to evaluate long term safety and efficacy of brivaracetam used as adjunctive treatment at a flexible dose up to a maximum of 200 mg/day in subjects aged 16 years or older suffering from epilepsy

    Summary
    EudraCT number
    2014-004397-42
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    18 Sep 2017

    Results information
    Results version number
    v2(current)
    This version publication date
    25 Nov 2018
    First version publication date
    05 Apr 2018
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    N01199
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00150800
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Pharma Inc.
    Sponsor organisation address
    1950 Lake Park Drive, Smyrna, United States, 30080
    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
    02 Nov 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Sep 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses with a maximum of 200 mg/day in subjects suffering from epilepsy.
    Protection of trial subjects
    During the conduct of the study all subjects were closely monitored.
    Background therapy
    Background therapy as permitted in the protocol.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    23 Jan 2006
    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
    Australia: 30
    Country: Number of subjects enrolled
    Brazil: 115
    Country: Number of subjects enrolled
    Canada: 13
    Country: Number of subjects enrolled
    India: 202
    Country: Number of subjects enrolled
    Mexico: 96
    Country: Number of subjects enrolled
    United States: 211
    Worldwide total number of subjects
    667
    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)
    0
    Adolescents (12-17 years)
    30
    Adults (18-64 years)
    632
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study started to enroll patients in January 2006 and concluded in September 2017. 668 subjects were included in the Enrolled Set but 1 subject from India lost to follow up and was excluded from the Safety Analysis Set due to lack of medical data.

    Pre-assignment
    Screening details
    The Participant Flow refers to the Safety Analysis Set which included all subjects who took at least 1 dose of study drug.

    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
    Brivaracetam
    Arm description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.
    Arm type
    Experimental

    Investigational medicinal product name
    Brivaracetam
    Investigational medicinal product code
    BRV
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Active investigational product (tablets containing 10 or 25 mg BRV) used as adjunctive treatment, flexible dosing up to 200 mg/day in b.i.d (twice daily) administration. Dose increase or decrease could be made in increments of maximum 50 mg/day on a weekly basis.

    Number of subjects in period 1
    Brivaracetam
    Started
    667
    Completed
    171
    Not completed
    496
         Pregnancy planned
    1
         Moved from area/country
    8
         Patient insurance
    1
         Visit refusal
    3
         BRV monotherapy
    1
         Generalized Epilepsy
    1
         Lack of efficacy
    166
         Nobody to accompany patient
    1
         Surgical intervention
    4
         Sponsor's request
    2
         Adverse event, serious fatal
    18
         Distance too long for patient
    1
         No compliance
    18
         Neurosurgery
    2
         PI discontinuation request
    1
         PI leaving site
    2
         Protocol non-adherence
    2
         Adverse event, non-fatal
    89
         PI retiring
    2
         Subject's choice
    90
         Lost to follow-up
    58
         IP misshandling
    1
         Site closure
    24

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Brivaracetam
    Reporting group description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.

    Reporting group values
    Brivaracetam Total
    Number of subjects
    667 667
    Age categorical
    Units: Subjects
        <=18 years
    30 30
        Between 18 and 65 years
    632 632
        >=65 years
    5 5
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    34.3 ± 12.2 -
    Gender categorical
    Units: Subjects
        Female
    303 303
        Male
    364 364

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Brivaracetam
    Reporting group description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.

    Subject analysis set title
    Brivaracetam (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.

    Subject analysis set title
    Brivaracetam (POS-ES)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.

    Primary: Percentage of participants with at least one Treatment-Emergent Adverse Event (TEAE) during the Study Period

    Close Top of page
    End point title
    Percentage of participants with at least one Treatment-Emergent Adverse Event (TEAE) during the Study Period [1]
    End point description
    Treatment-Emergent Adverse Events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
    End point type
    Primary
    End point timeframe
    Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 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 study. Results were summarized as descriptive statistics only.
    End point values
    Brivaracetam (SS)
    Number of subjects analysed
    667
    Units: percentage of participants
        number (not applicable)
    91.2
    No statistical analyses for this end point

    Primary: Percentage of participants who withdrew due to an Adverse Event (AE) during the Study Period

    Close Top of page
    End point title
    Percentage of participants who withdrew due to an Adverse Event (AE) during the Study Period [2]
    End point description
    Adverse Events (AE) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
    End point type
    Primary
    End point timeframe
    Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 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 study. Results were summarized as descriptive statistics only.
    End point values
    Brivaracetam (SS)
    Number of subjects analysed
    667
    Units: percentage of participants
        number (not applicable)
    14.8
    No statistical analyses for this end point

    Primary: Percentage of participants with a Serious Adverse Event (SAE) during the Study Period

    Close Top of page
    End point title
    Percentage of participants with a Serious Adverse Event (SAE) during the Study Period [3]
    End point description
    A Serious Adverse Event (SAE) is any untoward medical incidence that occurs at any dose.
    End point type
    Primary
    End point timeframe
    Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 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 study. Results were summarized as descriptive statistics only.
    End point values
    Brivaracetam (SS)
    Number of subjects analysed
    667
    Units: percentage of participants
        number (not applicable)
    22.8
    No statistical analyses for this end point

    Secondary: Partial Onset Seizure (POS) (type I) frequency per 28 days during the Evaluation Period

    Close Top of page
    End point title
    Partial Onset Seizure (POS) (type I) frequency per 28 days during the Evaluation Period
    End point description
    Baseline is the Baseline from subject's previous study of enrollment period. N01193 [NCT00175825], N01252 [NCT00490035], N01253 [NCT00464269], N01254 [NCT00504881]. A 28 day Type 1 seizure frequency is the total number of Type 1 seizures divided by the total number of days evaluated multiplied by 28.
    End point type
    Secondary
    End point timeframe
    From Baseline of the previous study to the Evaluation Period (up to 11 years)
    End point values
    Brivaracetam (POS-ES)
    Number of subjects analysed
    648
    Units: Seizures per 28 days
    median (inter-quartile range (Q1-Q3))
        baseline
    9.2 (5.5 to 20.2)
        on treatment
    4.2 (1.6 to 11.3)
    No statistical analyses for this end point

    Secondary: Percent change in Partial Onset Seizure (POS) (type I) frequency per 28 days from Baseline of the previous study to the Evaluation Period

    Close Top of page
    End point title
    Percent change in Partial Onset Seizure (POS) (type I) frequency per 28 days from Baseline of the previous study to the Evaluation Period
    End point description
    The percent change from the previous study baselines, in Partial Onset Seizure (POS) (Type I) frequency per 28 days is defined as: (the value at the previous study baselines) minus (the value at each time-points during the evaluation period) divided by the value at the previous study baselines.
    End point type
    Secondary
    End point timeframe
    From Baseline of the previous study to the Evaluation Period (up to 11 years)
    End point values
    Brivaracetam (POS-ES)
    Number of subjects analysed
    648
    Units: percent change
        median (inter-quartile range (Q1-Q3))
    57.3 (18.6 to 82.2)
    No statistical analyses for this end point

    Secondary: Percentage of participants with response for Partial Onset Seizure (POS) (type I) frequency over the Evaluation Period

    Close Top of page
    End point title
    Percentage of participants with response for Partial Onset Seizure (POS) (type I) frequency over the Evaluation Period
    End point description
    A responder is defined as a subject with a higher than or equal to (>=) 50 % change in seizure frequency from Baseline period of the previous study.
    End point type
    Secondary
    End point timeframe
    From Baseline of the previous study to the Evaluation Period (up to 11 years)
    End point values
    Brivaracetam (POS-ES)
    Number of subjects analysed
    648
    Units: percentage of participants
        number (not applicable)
    55.6
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Brivaracetam
    Reporting group description
    Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis.

    Serious adverse events
    Brivaracetam
    Total subjects affected by serious adverse events
         subjects affected / exposed
    152 / 667 (22.79%)
         number of deaths (all causes)
    18
         number of deaths resulting from adverse events
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain cancer metastatic
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Brain neoplasm
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lipoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Metastatic bronchial carcinoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Ocular neoplasm
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ovarian epithelial cancer
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Oesophageal cancer metastatic
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small cell lung cancer stage unspecified
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestine carcinoma metastatic
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Uterine leiomyoma
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pregnancy
         subjects affected / exposed
    5 / 667 (0.75%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Foetal death
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Pregnancy on contraceptive
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pregnancy on oral contraceptive
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Unintended pregnancy
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Drug ineffective
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Sudden unexplained death in epilepsy
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    1 / 2
    Pyrexia
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Unevaluable event
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Aggression
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Completed suicide
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    1 / 2
    Depression
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paranoia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Schizophrenia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Self-injurious ideation
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Suicide attempt
         subjects affected / exposed
    7 / 667 (1.05%)
         occurrences causally related to treatment / all
    5 / 8
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Menorrhagia
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Scrotal disorder
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal injury
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Accident
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Anastomotic ulcer
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Animal bite
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ankle fracture
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Burns third degree
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    Craniocerebral injury
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Humerus fracture
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thermal burn
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    4 / 667 (0.60%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Ulna fracture
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Anticonvulsant drug level increased
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Weight increased
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    Myocardial ischaemia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asphyxia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Asthma
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infiltration
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Complicated migraine
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Convulsion
         subjects affected / exposed
    15 / 667 (2.25%)
         occurrences causally related to treatment / all
    4 / 20
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Headache
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Partial seizures
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Postictal state
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Seizure cluster
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Somnolence
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Status epilepticus
         subjects affected / exposed
    6 / 667 (0.90%)
         occurrences causally related to treatment / all
    4 / 7
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 667 (0.60%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric fistula
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Splenic artery aneurysm
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure acute
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Joint instability
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperammonaemia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Hypoproteinaemia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coccidioidomycosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dengue fever
         subjects affected / exposed
    2 / 667 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Disseminated tuberculosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Encephalitis herpes
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malaria
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mastoiditis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Meningitis tuberculous
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Neurocysticercosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic inflammatory disease
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 667 (1.05%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rickettsiosis
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 667 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 667 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 667 (0.15%)
         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
    Brivaracetam
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    521 / 667 (78.11%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    46 / 667 (6.90%)
         occurrences all number
    55
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    40 / 667 (6.00%)
         occurrences all number
    72
    Contusion
         subjects affected / exposed
    34 / 667 (5.10%)
         occurrences all number
    68
    Laceration
         subjects affected / exposed
    34 / 667 (5.10%)
         occurrences all number
    65
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    46 / 667 (6.90%)
         occurrences all number
    69
    Nervous system disorders
    Headache
         subjects affected / exposed
    165 / 667 (24.74%)
         occurrences all number
    420
    Dizziness
         subjects affected / exposed
    142 / 667 (21.29%)
         occurrences all number
    254
    Somnolence
         subjects affected / exposed
    91 / 667 (13.64%)
         occurrences all number
    116
    Tremor
         subjects affected / exposed
    38 / 667 (5.70%)
         occurrences all number
    48
    Convulsion
         subjects affected / exposed
    70 / 667 (10.49%)
         occurrences all number
    99
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    69 / 667 (10.34%)
         occurrences all number
    132
    Irritability
         subjects affected / exposed
    42 / 667 (6.30%)
         occurrences all number
    50
    Fatigue
         subjects affected / exposed
    51 / 667 (7.65%)
         occurrences all number
    63
    Psychiatric disorders
    Depression
         subjects affected / exposed
    70 / 667 (10.49%)
         occurrences all number
    85
    Insomnia
         subjects affected / exposed
    49 / 667 (7.35%)
         occurrences all number
    65
    Anxiety
         subjects affected / exposed
    45 / 667 (6.75%)
         occurrences all number
    65
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    67 / 667 (10.04%)
         occurrences all number
    93
    Diarrhoea
         subjects affected / exposed
    65 / 667 (9.75%)
         occurrences all number
    86
    Vomiting
         subjects affected / exposed
    58 / 667 (8.70%)
         occurrences all number
    109
    Abdominal pain
         subjects affected / exposed
    39 / 667 (5.85%)
         occurrences all number
    55
    Toothache
         subjects affected / exposed
    42 / 667 (6.30%)
         occurrences all number
    66
    Constipation
         subjects affected / exposed
    38 / 667 (5.70%)
         occurrences all number
    48
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    34 / 667 (5.10%)
         occurrences all number
    56
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    64 / 667 (9.60%)
         occurrences all number
    88
    Arthralgia
         subjects affected / exposed
    52 / 667 (7.80%)
         occurrences all number
    66
    Pain in extremity
    alternative assessment type: Systematic
         subjects affected / exposed
    44 / 667 (6.60%)
         occurrences all number
    63
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    36 / 667 (5.40%)
         occurrences all number
    41
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    94 / 667 (14.09%)
         occurrences all number
    154
    Upper respiratory tract infection
         subjects affected / exposed
    76 / 667 (11.39%)
         occurrences all number
    137
    Influenza
         subjects affected / exposed
    84 / 667 (12.59%)
         occurrences all number
    177
    Urinary tract infection
         subjects affected / exposed
    64 / 667 (9.60%)
         occurrences all number
    150

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Jun 2006
    Clarified several sections of the protocol, including study title, study drug packaging, flow chart, study procedures and visit description, and Sponsor contact information.
    02 Mar 2007
    Permitted participation of subjects from the brivaracetam (BRV) Phase 3 studies (N01253, N01253, and N01254) and updates of several sections including study title, background information, exclusion criteria, objectives, variables, and the study schematic. Maximum dose of study drug was increased to 150 mg/day.
    01 Jun 2007
    Issued as a follow-up to the Food and Drug Administration (FDA) feedback received on study N01253 where FDA specifically requested to add an additional down-titration step for subjects taking 50 mg/day or more. The use of the 2.5 mg tablets was restricted to subjects taking less than BRV 40 mg/day. Additional clarifications were made to allow for a new Clinical Trial Manager, clarify additional information from Amendment 2, and update some minor typographical errors.
    20 May 2008
    Clarified that subjects rolling over from the Phase 2 brivaracetam (BRV) study, N01193, who were on placebo would have access to BRV, updated the inclusion criterion regarding contraceptive methods, and stipulated that dose increments were to be made using only 10 mg or 25 mg tablets beyond the dose of 40 mg/day.
    26 Jun 2011
    Introduced the increased maximum dose of brivaracetam (BRV) of 200 mg/day; provided that conversion to monotherapy would no longer be at the Investigator’s discretion; updated procedures for reporting serious adverse events (SAEs) to implement Food and Drug Administration (FDA) Final Rule requirements; updated laboratory assessments (BRV and antiepileptic drug (AED) plasma levels were no longer obtained), statistical analyses, and contact information; reduced the number of study assessments; limited the assessments of exploratory variables (Patient Weighted Quality of Life in Epilepsy Questionnaire [QOLIE-31-P], Hospital Anxiety and Depression Scale [HADS], EuroQoL 5 Dimensions Questionnaire [EQ-5D], hospital stays, healthcare provider consultations not foreseen, school and work days lost, and socioprofessional data) to the first 2 years after study entry; added the Columbia Suicide Severity Rating Scale (C-SSRS) and respective withdrawal criteria; introduced a Partner Pregnancy Consent form; removal of 2.5 mg tablets; removal of references to subjects coming from N01258, since these subjects were no longer to be included in N01199; and made further minor changes for consistency between BRV studies.
    15 Oct 2015
    Aligned efficacy variables in statistics section with current N01199 statistical analysis plan (SAP); the study duration language was revised to include the possibility of a named patient or compassionate use program (or similar) as a reason for ending the study duration; language regarding Investigator deviation from the protocol in the event of a medical emergency was revised to align with current UCB standard language.

    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
    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