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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    Multicenter, Double-Blind, Randomized, Placebo-Controlled, Three-Arm, Parallel Group Study to Evaluate the Efficacy and Safety of Oxcarbazepine Extended-Release (OXC XR) (1200 and 2400mg/day) as Adjunctive Therapy in Subjects with Refractory Partial Seizures due to Epilepsy on up to Three Concomitant Anti-epileptic Medications

    Summary
    EudraCT number
    		 2008-003333-25
    Trial protocol
    		 BG  
    Global end of trial date
    29 Nov 2010

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jun 2022
    First version publication date
    24 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    804P301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00772603
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Supernus Pharmaceuticals, Inc.
    Sponsor organisation address
    9715 Key West Avenue, Rockville, MD, United States, 20850
    Public contact
    Jonathan Rubin, MD, Supernus Pharmaceuticals, Inc., jrubin@supernus.com
    Scientific contact
    Joseph T. Hull, PhD, Supernus Pharmaceuticals, Inc., jhull@supernus.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Aug 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Nov 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Nov 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of adjunctive OXC XR (Supernus Pharmaceuticals, Inc.) in the treatment of seizures of partial origin in adults with refractory epilepsy on at least one and up to three other anti-epileptic drugs (AEDs).
    Protection of trial subjects
    All potential study participants provided informed consent and were screened to determine his/her eligibility to participate in the study. The screening included a review of medical history and concomitant medication, evaluation of subject's seizure type and frequency, and performing the following clinical assessments: physical exam, neurological exam, vital signs (including blood pressure, pulse rate, respiratory rate, oral body temperature), measure weight and height (body mass index), clinical laboratory testing (hematology/chemistry), electrocardiogram and urine pregnancy test for women of childbearing potential. Eligible subjects who met the inclusion/exclusion criteria, randomized and received study medication were monitored throughout the study, including the above mentioned clinical assessments performed at study visits and assessing concomitant medications and adverse events during treatment and at the end of study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Oct 2008
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Russian Federation: 90
    Country: Number of subjects enrolled
    United States: 69
    Country: Number of subjects enrolled
    Poland: 54
    Country: Number of subjects enrolled
    Mexico: 45
    Country: Number of subjects enrolled
    Romania: 24
    Country: Number of subjects enrolled
    Bulgaria: 53
    Country: Number of subjects enrolled
    Croatia: 29
    Worldwide total number of subjects
    366
    EEA total number of subjects
    160
    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)
    0
    Adults (18-64 years)
    365
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study started to enroll subjects in October of 2008. Randomization of subjects began the earliest in the U.S. (29Dec2008) and later in Mexico (05Oct2009), Eastern Europe (13Nov2009), and Russia (11Feb2010).

    Pre-assignment
    Screening details
    		 Adult males and females between 18 and 65 years of age with refractory partial-onset epilepsy of at least 3 countable partial seizures per 28 days on average and being treated with 1 to 3 antiepileptic drugs were eligible. There were 440 subjects screened, 366 subjects randomized, 248 subjects completed the study, and 118 subjects discontinued.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomization for this study was managed centrally by an interactive voice response system (IVRS). Subjects were assigned to OXC XR 2400mg, OXC XR 1200mg, or placebo in a 1:1:1 ratio. During double-blind trial, the subject and all personnel involved with the conduct and interpretation of the study, including Investigators, study site personnel, and Sponsor and CRO clinical staff, will be blinded to treatment assignment. Regardless of treatment assignment, subjects took 4 tablets orally daily.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects take four identical tablets orally once daily. All four tablets are non-active and are identical to active tablets.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will take placebo QD along with adjunctive therapy with stable doses of at least one and up to three other AEDs.

    Arm title
    		 2400mg/day SPN-804
    Arm description
    		 Subjects take four identical tablets orally once daily. All four tablets are active drug each containing 600mg OXC XR and are identical to non-active tablets.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oxcarbazepine extended-release (OXC XR)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will take 2400mg total daily dose of OXC XR once a day (QD) along with adjunctive therapy with stable doses of at least one and up to three other AEDs (cannot include OXC).

    Arm title
    		 1200mg/day SPN-804
    Arm description
    		 Subjects take four identical tablets orally once daily. Two tablets are active drug each containing 600mg OXC XR and the other two tablets are non-active.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oxcarbazepine extended-release (OXC XR)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will take 1200mg total daily dose of OXC XR once a day (QD) along with adjunctive therapy with stable doses of at least one and up to three other AEDs (cannot include OXC).

    Number of subjects in period 1
    		Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Started
    121
    123
    122
    Completed
    95
    71
    82
    Not completed
    26
    52
    40
         Consent withdrawn by subject
    6
    11
    10
         Physician decision
    1
    -
    -
         Others
    -
    2
    -
         Adverse event, non-fatal
    10
    37
    18
         Other
    2
    -
    -
         Subject Non-compliance
    4
    1
    6
         Protocol Violation
    1
    -
    1
         Lost to follow-up
    2
    1
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are non-active and are identical to active tablets.

    Reporting group title
    2400mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are active drug each containing 600mg OXC XR and are identical to non-active tablets.

    Reporting group title
    1200mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. Two tablets are active drug each containing 600mg OXC XR and the other two tablets are non-active.

    Reporting group values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804 Total
    Number of subjects
    		 121 123 122 366
    Age categorical
    Number of Adult Subjects by Age Category by Treatment Group
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 120 123 122 365
        From 65-84 years
    		 1 0 0 1
        85 years and over
    		 0 0 0 0
    Age continuous
    Mean and Standard Deviation of Adult Subjects by Treatment Group
    Units: years
        arithmetic mean (standard deviation)
    		 39.1 ( 12.49 ) 38.5 ( 11.58 ) 39.1 ( 11.51 ) -
    Gender categorical
    Number of Male and Female Subjects by Treatment Group
    Units: Subjects
        Female
    		 67 64 71 202
        Male
    		 54 59 51 164
    Race
    Number of Subjects By Race by Treatment Group
    Units: Subjects
        White
    		 112 108 108 328
        Black
    		 1 1 5 7
        Asian
    		 0 1 1 2
        American Indian or Alaska Native
    		 0 1 0 1
        Other
    		 8 12 8 28

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are non-active and are identical to active tablets.

    Reporting group title
    2400mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are active drug each containing 600mg OXC XR and are identical to non-active tablets.

    Reporting group title
    1200mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. Two tablets are active drug each containing 600mg OXC XR and the other two tablets are non-active.

    Primary: Percent change from baseline in seizure frequency during Treatment Phase (Primary Efficacy Endpoint)

    		 Close Top of page
    End point title
    		 Percent change from baseline in seizure frequency during Treatment Phase (Primary Efficacy Endpoint)
    End point description
    The primary efficacy endpoint is the median percent change from baseline in seizure frequency per 28 days during Treatment Phase (4 weeks Titration Period + 12 weeks Maintenance Period). This analysis included randomized subjects who took at least one dose of study medication, had seizure diary data during the Baseline Phase, and completed at least one study visit during the Treatment Phase.
    End point type
    Primary
    End point timeframe
    Change at 16 weeks (4 weeks Titration + 12 weeks Maintenance) compared to Baseline
    End point values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Number of subjects analysed
    117
    111
    109
    Units: percent
        median (full range (min-max))
    -28.70 (-100.0 to 333.6)
    -42.90 (-100.0 to 212.8)
    -38.20 (-100.0 to 556.1)
    Statistical analysis title
    		 Statistical Analysis 1: 2400mg SPN-804 vs Placebo
    Statistical analysis description
    A Wilcoxon rank-sum test was used to test hypothesis that there is no difference in the median percent change from baseline in seizure frequency per 28 days during Treatment Phase between SPN-804 and placebo. The sample size of 120 patients per treatment arm provides over 95% power to detect a difference of 31% to 42% between placebo and 2400mg SPN-804 at a two-sided 0.025 level for an overall Type I error rate of 0.050.
    Comparison groups
    2400mg/day SPN-804 v Placebo
    Number of subjects included in analysis
    228
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [1]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Point estimate
    -18.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.4
         upper limit
    		 -5.8
    Notes
    [1] - P-values reported are not adjusted for multiple comparisons. To preserve the overall Type I error-rate at 0.050, a step-up Hochberg procedure was used for the pair-wise comparisons.
    Statistical analysis title
    		 Statistical Analysis 2: 1200mg SPN-804 vs Placebo
    Statistical analysis description
    A Wilcoxon rank-sum test was used to test hypothesis that there is no difference in the median percent change from baseline in seizure frequency per 28 days during Treatment Phase between SPN-804 and placebo. The sample size of 120 patients per treatment arm provides over 95% power to detect a difference of 24% to 32% between placebo and 1200mg SPN-804 at a two-sided 0.025 level for an overall Type I error rate of 0.050.
    Comparison groups
    1200mg/day SPN-804 v Placebo
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.078 [2]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Point estimate
    -10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.3
         upper limit
    		 1.2
    Notes
    [2] - P values reported are not adjusted for multiple comparisons. To preserve the overall Type I error-rate at 0.050, a step-up Hochberg procedure was used for the pair-wise comparisons.

    Secondary: Percent change from baseline in seizure frequency during Maintenance Period (Secondary Efficacy Endpoint)

    		 Close Top of page
    End point title
    		 Percent change from baseline in seizure frequency during Maintenance Period (Secondary Efficacy Endpoint)
    End point description
    A secondary efficacy endpoint is the median percent change (PCH) from baseline in seizure frequency per 28 days during Maintenance Period (12 weeks) of the Treatment Phase. This analysis included randomized subjects who took at least one dose of study medication, had seizure diary data during the Baseline Phase, and completed at least one study visit during the Titration Period and one study visit during the Maintenance Period of the Treatment Phase.
    End point type
    Secondary
    End point timeframe
    Change at 12 weeks (Maintenance Period) compared to Baseline
    End point values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Number of subjects analysed
    109
    88
    97
    Units: percent
        median (full range (min-max))
    -32.90 (-100.0 to 212.6)
    -49.15 (-100.0 to 158.0)
    -35.30 (-100.0 to 690.5)
    Statistical analysis title
    		 Statistical Analysis 1: 2400mg SPN-804 vs Placebo
    Statistical analysis description
    A Wilcoxon rank-sum test was used to test hypothesis that there is no difference in the median percent change from baseline in seizure frequency per 28 days during Maintenance between SPN-804 and placebo. The sample size of 120 patients per treatment arm provides over 95% power to detect a difference of 31% to 42% between placebo and 2400mg SPN-804 at a two-sided 0.025 level for an overall Type I error rate of 0.050.
    Comparison groups
    Placebo v 2400mg/day SPN-804
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004 [3]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Point estimate
    -20.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33
         upper limit
    		 -6.3
    Notes
    [3] - P-values reported are not adjusted for multiple comparisons. To preserve the overall Type I error-rate at 0.050, a step-up Hochberg procedure was used for the pair-wise comparisons.
    Statistical analysis title
    		 Statistical Analysis 2: 1200mg SPN-804 vs Placebo
    Statistical analysis description
    A Wilcoxon rank-sum test was used to test hypothesis that there is no difference in the median percent change from baseline in seizure frequency per 28 days during Maintenance between SPN-804 and placebo. The sample size of 120 patients per treatment arm provides over 95% power to detect a difference of 24% to 32% between placebo and 1200mg SPN-804 at a two-sided 0.025 level for an overall Type I error rate of 0.050.
    Comparison groups
    1200mg/day SPN-804 v Placebo
    Number of subjects included in analysis
    206
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.589 [4]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.2
         upper limit
    		 9.7
    Notes
    [4] - P-values reported are not adjusted for multiple comparisons. To preserve the overall Type I error-rate at 0.050, a step-up Hochberg procedure was used for the pair-wise comparisons.

    Secondary: Responder Rate at end of Treatment Phase (Secondary Efficacy Endpoint)

    		 Close Top of page
    End point title
    		 Responder Rate at end of Treatment Phase (Secondary Efficacy Endpoint)
    End point description
    A secondary efficacy endpoint is the percentage of subjects with a positive response (defined as a 50% or greater reduction in the change from baseline seizure frequency per 28 days) at end of Treatment Phase. This analysis included randomized subjects who took at least one dose of study medication, had seizure diary data during the Baseline Phase, and completed at least one study visit during the Treatment Phase.
    End point type
    Secondary
    End point timeframe
    At the end of 16 weeks (4 wks Titration + 12 wks Maintenance)
    End point values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Number of subjects analysed
    121
    123
    122
    Units: percent
        number (not applicable)
    28.1
    40.7
    36.1
    Statistical analysis title
    		 Statistical Analysis 1: 2400mg SPN-804 vs Placebo
    Statistical analysis description
    The treatment response was analyzed using a logistic regression model with treatment group as a factor and country (or cluster), age, sex, and baseline seizure frequency per 28 days as explanatory variables.
    Comparison groups
    Placebo v 2400mg/day SPN-804
    Number of subjects included in analysis
    244
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.018
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.983
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.126
         upper limit
    		 3.494
    Notes
    [5] - The treatment response was analyzed using a logistic regression model with treatment group as a factor and country (or cluster), age, sex, and baseline seizure frequency per 28 days as explanatory variables.
    Statistical analysis title
    		 Statistical Analysis 2: 1200mg SPN-804 vs Placebo
    Statistical analysis description
    The treatment response was analyzed using a logistic regression model with treatment group as a factor and country (or cluster), age, sex, and baseline seizure frequency per 28 days as explanatory variables.
    Comparison groups
    1200mg/day SPN-804 v Placebo
    Number of subjects included in analysis
    243
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.075
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 2.937

    Secondary: Seizure-Free Rates during the Treatment Phase (Secondary Efficacy Endpoint)

    		 Close Top of page
    End point title
    		 Seizure-Free Rates during the Treatment Phase (Secondary Efficacy Endpoint)
    End point description
    A secondary efficacy endpoint is the percentage of subjects who did not experience a seizure during the Treatment Phase. This analysis included randomized subjects who took at least one dose of study medication, had seizure diary data during the Baseline Phase, and completed at least one study visit during the Treatment Phase.
    End point type
    Secondary
    End point timeframe
    At the end of 16 weeks (4 wks Titration + 12 wks Maintenance)
    End point values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Number of subjects analysed
    121
    123
    122
    Units: percent
        number (not applicable)
    3.3
    11.4
    4.9
    Statistical analysis title
    		 Statistical Analysis 1: 2400mg SPN-804 vs Placebo
    Statistical analysis description
    Pairwise comparisons of OXC XR 2400mg/day vs. placebo seizure-free rates during the Treatment Phase were made by means of Fisher's exact test for the ITT population.
    Comparison groups
    Placebo v 2400mg/day SPN-804
    Number of subjects included in analysis
    244
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.013
    Method
    		 Fisher exact
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2: 1200mg SPN-804 vs Placebo
    Statistical analysis description
    Pairwise comparisons of OXC XR 1200mg/day vs. placebo seizure-free rates during the Treatment Phase were made by means of Fisher's exact test for the ITT population.
    Comparison groups
    Placebo v 1200mg/day SPN-804
    Number of subjects included in analysis
    243
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.528
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Seizure Free Rate during Maintenance Period (Secondary Efficacy Endpoint)

    		 Close Top of page
    End point title
    		 Seizure Free Rate during Maintenance Period (Secondary Efficacy Endpoint)
    End point description
    A secondary efficacy endpoint is the percentage of subjects who did not experience a seizure during Maintenance Period of Treatment Phase. This analysis included randomized subjects who took at least one dose of study medication, had seizure diary data during the Baseline Phase, and completed at least one study visit during the Titration Period and one study visit during the Maintenance Period of the Treatment Phase.
    End point type
    Secondary
    End point timeframe
    At the end of 12 weeks (Maintenance Period)
    End point values
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Number of subjects analysed
    121
    123
    122
    Units: percent
        number (not applicable)
    5.8
    13.8
    3.3
    Statistical analysis title
    		 Statistical Analysis 1: 2400mg SPN-804 vs Placebo
    Statistical analysis description
    Pairwise comparisons of OXC XR 2400mg/day vs. placebo seizure-free rates during the Maintenance Period were made by means of Fisher's exact test for the ITT population.
    Comparison groups
    Placebo v 2400mg/day SPN-804
    Number of subjects included in analysis
    244
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008
    Method
    		 Fisher exact
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2: 1200mg SPN-804 vs Placebo
    Statistical analysis description
    Pairwise comparisons of OXC XR 1200mg/day vs. placebo seizure-free rates during the Maintenance Period were made by means of Fisher's exact test for the ITT population.
    Comparison groups
    1200mg/day SPN-804 v Placebo
    Number of subjects included in analysis
    243
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.546
    Method
    		 Fisher exact
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 20 weeks (4 weeks Titration + 12 Weeks Maintenance + up to 4 weeks Tapering/Conversion)
    Adverse event reporting additional description
    The number of subjects reported in each treatment arm for serious adverse events and non-serious adverse events is based on the Safety Population, defined as all randomized subjects who took at least one dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are non-active and are identical to active tablets.

    Reporting group title
    2400mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. All four tablets are active drug each containing 600mg OXC XR and are identical to non-active tablets.

    Reporting group title
    1200mg/day SPN-804
    Reporting group description
    		 Subjects take four identical tablets orally once daily. Two tablets are active drug each containing 600mg OXC XR and the other two tablets are non-active.

    Serious adverse events
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 121 (5.79%)
    10 / 123 (8.13%)
    7 / 122 (5.74%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lactate dehydrogenase increased
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Ovarian cancer
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull fractured base
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsions/complex partial seizures
         subjects affected / exposed
    1 / 121 (0.83%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 121 (0.83%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 121 (0.00%)
    2 / 123 (1.63%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nystagmus
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post-ictal state
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drug intolerance
         subjects affected / exposed
    0 / 121 (0.00%)
    2 / 123 (1.63%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pityriasis rosea
         subjects affected / exposed
    0 / 121 (0.00%)
    0 / 123 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash erythematous
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash generalized
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stevens-Johnson Syndrome
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 121 (0.83%)
    0 / 123 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatreamia
         subjects affected / exposed
    0 / 121 (0.00%)
    1 / 123 (0.81%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0.05%
    Non-serious adverse events
    		 Placebo 2400mg/day SPN-804 1200mg/day SPN-804
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    55 / 121 (45.45%)
    69 / 123 (56.10%)
    57 / 122 (46.72%)
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    6 / 121 (4.96%)
    8 / 123 (6.50%)
    6 / 122 (4.92%)
         occurrences all number
    7
    12
    11
    Dizziness
         subjects affected / exposed
    18 / 121 (14.88%)
    50 / 123 (40.65%)
    24 / 122 (19.67%)
         occurrences all number
    21
    60
    30
    Headache
         subjects affected / exposed
    9 / 121 (7.44%)
    19 / 123 (15.45%)
    10 / 122 (8.20%)
         occurrences all number
    12
    21
    10
    Somnolence
         subjects affected / exposed
    11 / 121 (9.09%)
    17 / 123 (13.82%)
    14 / 122 (11.48%)
         occurrences all number
    12
    19
    14
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 121 (0.83%)
    9 / 123 (7.32%)
    4 / 122 (3.28%)
         occurrences all number
    2
    9
    4
    Fatigue
         subjects affected / exposed
    1 / 121 (0.83%)
    4 / 123 (3.25%)
    7 / 122 (5.74%)
         occurrences all number
    1
    5
    7
    Eye disorders
    Diplopia
         subjects affected / exposed
    5 / 121 (4.13%)
    16 / 123 (13.01%)
    12 / 122 (9.84%)
         occurrences all number
    5
    21
    15
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    11 / 121 (9.09%)
    19 / 123 (15.45%)
    7 / 122 (5.74%)
         occurrences all number
    11
    20
    10

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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.

    European Medicines Agency © 1995-Tue May 07 02:50:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA