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    Clinical Trial Results:
    A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Children and Young Adults with Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) Followed by Long-term Open-label Treatment

    Summary
    EudraCT number
    		 2018-001180-23
    Trial protocol
    		 GB   IT   FR   PL  
    Global end of trial date
    28 May 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2025
    First version publication date
    20 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    1042-CDD-3001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03572933
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Marinus Pharmaceuticals, Inc.
    Sponsor organisation address
    5 Radnor Corporate Center, 100 Matsonford Road, Suite 500, Radnor, PA, United States, 19087
    Public contact
    Safety Department, Marinus Pharmaceuticals, Inc., +46 853339500, clinical@immedica.com
    Scientific contact
    Safety Department, Marinus Pharmaceuticals, Inc., +46 853339500, clinical@immedica.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
    28 May 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 May 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.
    Protection of trial subjects
    At the first visit, prior to initiation of any study-related procedures, the parent(s) or legal guardian(s) of the subjects gave their written consent to participate in the study after having been informed about the nature and purpose of the study, participation / termination conditions, and risks and benefits. Before the informed consent document was signed, the investigator, or a person designated by the investigator, provided the subject or the subject's legally acceptable representative ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial were answered to the satisfaction of the subject or the subject's legally acceptable representative.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 6
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    United States: 42
    Country: Number of subjects enrolled
    Poland: 10
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Italy: 15
    Worldwide total number of subjects
    101
    EEA total number of subjects
    31
    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)
    82
    Adolescents (12-17 years)
    17
    Adults (18-64 years)
    2
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study was to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Placebo suspension 3x's /day for 17 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was administered

    Arm title
    		 Ganaxolone
    Arm description
    		 Ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ganaxolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Ganaxolone was administered

    Number of subjects in period 1
    		Placebo Ganaxolone
    Started
    51
    50
    Completed
    47
    48
    Not completed
    4
    2
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    4
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo suspension 3x's /day for 17 weeks

    Reporting group title
    Ganaxolone
    Reporting group description
    		 Ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks

    Reporting group values
    		 Placebo Ganaxolone Total
    Number of subjects
    		 51 50 101
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 41 41 82
        Adolescents (12-17 years)
    		 9 8 17
        Adults (18-64 years)
    		 1 1 2
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 7.73 ( 4.382 ) 6.78 ( 4.705 ) -
    Gender categorical
    Units: Subjects
        Female
    		 41 39 80
        Male
    		 10 11 21
    Race
    Units: Subjects
        Asian
    		 3 2 5
        White
    		 47 46 93
        Unknown or Not Reported
    		 1 2 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 6 4 10
        Not Hispanic or Latino
    		 43 44 87
        Unknown or Not Reported
    		 2 2 4

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo suspension 3x's /day for 17 weeks

    Reporting group title
    Ganaxolone
    Reporting group description
    		 Ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks

    Primary: Summary of 28-day Seizure Frequency for Major Motor Seizure Types

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    End point title
    		 Summary of 28-day Seizure Frequency for Major Motor Seizure Types [1]
    End point description
    Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period. Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28. Intent-to-Treat (ITT) population: included all randomized participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    End of the double-blind 17 week treatment period
    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 statistical analysis was performed for this outcome measure.
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    51
    49
    Units: Seizures per day
    median (confidence interval 95%)
        Baseline
    49.17 (32.20 to 60.67)
    54.00 (38.24 to 106.67)
        17 week-post baseline phase
    55.50 (35.75 to 80.14)
    45.03 (31.83 to 76.03)
    No statistical analyses for this end point

    Secondary: Caregiver Global Impression of Change in Attention

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    End point title
    		 Caregiver Global Impression of Change in Attention
    End point description
    Caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives. Per Protocol population: included ITT participants who received study drug for at least 6 weeks, provided at least 5 weeks of post-baseline seizure data, and had no major protocol violations. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    47
    45
    Units: Participants
    number (not applicable)
        Very Much Improved - Visit 5 (End of Week 17)
    1
    1
        Much Improved - Visit 5 (End of Week 17)
    7
    2
        Minimally Improved - Visit 5 (End of Week 17)
    14
    21
        No Change - Visit 5 (End of Week 17)
    23
    18
        Minimally Worse - Visit 5 (End of Week 17)
    1
    1
        Much Worse - Visit 5 (End of Week 17)
    1
    1
        Very Much Worse - Visit 5 (End of Week 17)
    0
    1
    No statistical analyses for this end point

    Secondary: Caregiver Global Impression of Change in Target Behavior

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    End point title
    		 Caregiver Global Impression of Change in Target Behavior
    End point description
    Caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    46
    45
    Units: Participants
    number (not applicable)
        Very Much Improved - Visit 5 (End of Week 17)
    0
    0
        Much Improved - Visit 5 (End of Week 17)
    6
    4
        Minimally Improved - Visit 5 (End of Week 17)
    14
    20
        No Change - Visit 5 (End of Week 17)
    22
    19
        Minimally Worse - Visit 5 (End of Week 17)
    1
    2
        Much Worse - Visit 5 (End of Week 17)
    2
    0
        Very Much Worse - Visit 5 (End of Week 17)
    1
    0
    No statistical analyses for this end point

    Secondary: Clinical Global Impression of Improvement - Parent/Caregiver (P/C)

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    End point title
    		 Clinical Global Impression of Improvement - Parent/Caregiver (P/C)
    End point description
    Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    48
    48
    Units: Participants
    number (not applicable)
        Very Much Improved - Visit 5 (End of Week 17)- P/C
    1
    0
        Much Improved - Visit 5 (End of Week 17) - P/C
    7
    13
        Minimally Improved - Visit 5 (End of Week 17)-P/C
    13
    17
        No Change - Visit 5 (End of Week 17) - P/C
    22
    14
        Minimally Worse - Visit 5 (End of Week 17) - P/C
    4
    2
        Much Worse - Visit 5 (End of Week 17) - P/C
    1
    2
        Very Much Worse - Visit 5 (End of Week 17) - P/C
    0
    0
    No statistical analyses for this end point

    Secondary: Clinical Global Impression of Improvement - Clinician (C)

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    End point title
    		 Clinical Global Impression of Improvement - Clinician (C)
    End point description
    Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    48
    48
    Units: Participants
    number (not applicable)
        Very Much Improved - Visit 5 (End of Week 17)- C
    0
    0
        Much Improved - Visit 5 (End of Week 17) - C
    7
    7
        Minimally Improved - Visit 5 (End of Week 17) - C
    13
    19
        No Change - Visit 5 (End of Week 17) - C
    19
    16
        Minimally Worse - Visit 5 (End of Week 17) - C
    9
    2
        Much Worse - Visit 5 (End of Week 17) - C
    0
    3
        Very Much Worse - Visit 5 (End of Week 17) - C
    0
    1
    No statistical analyses for this end point

    Secondary: Percentage of Seizure-free Days for Major Motor Seizure Types

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    End point title
    		 Percentage of Seizure-free Days for Major Motor Seizure Types
    End point description
    Percentage of Seizure-free Days for Major Motor Seizure types during the double-blind treatment period of ganaxolone compared to placebo. The major motor seizure types include bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, atonic/drop, bilateral clonic, and focal to bilateral tonic-clonic.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    51
    50
    Units: Percent of seizure-free days
    arithmetic mean (standard deviation)
        Baseline
    30.32 ( 27.070 )
    22.57 ( 25.761 )
        17-week-Post-Baseline Phase
    36.17 ( 30.932 )
    32.29 ( 30.615 )
        Arithmetic Change from Baseline
    5.86 ( 15.350 )
    9.62 ( 21.364 )
    No statistical analyses for this end point

    Secondary: Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types

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    End point title
    		 Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
    End point description
    Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    51
    49
    Units: Days
        arithmetic mean (standard deviation)
    -4.68 ( 14.831 )
    -0.02 ( 9.376 )
    No statistical analyses for this end point

    Secondary: Caregiver Global Impression of Change in Seizure Intensity and Duration

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    End point title
    		 Caregiver Global Impression of Change in Seizure Intensity and Duration
    End point description
    Caregiver global impression of change in seizure intensity and duration during the double-blind treatment period of ganaxolone compared to placebo. CGI-C is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    End of the double-blind 17 week treatment period
    End point values
    		 Placebo Ganaxolone
    Number of subjects analysed
    47
    45
    Units: Participants
    number (not applicable)
        Very Much Improved - Visit 5 (End of Week 17)
    1
    2
        Much Improved - Visit 5 (End of Week 17)
    5
    15
        Minimally Improved - Visit 5 (End of Week 17)
    11
    11
        No Change - Visit 5 (End of Week 17)
    21
    10
        Minimally Worse - Visit 5 (End of Week 17)
    5
    3
        Much Worse - Visit 5 (End of Week 17)
    4
    2
        Very Much Worse - Visit 5 (End of Week 17)
    0
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Screening through 17-week Double-blind Phase
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo suspension 3x's /day for 17 weeks

    Reporting group title
    Ganaxolone
    Reporting group description
    		 Ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks

    Serious adverse events
    		 Placebo Ganaxolone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 51 (9.80%)
    6 / 50 (12.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal disorders
    Faecaloma
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypotonia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Food refusal
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Ganaxolone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    45 / 51 (88.24%)
    43 / 50 (86.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign breast neoplasm
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 51 (7.84%)
    9 / 50 (18.00%)
         occurrences all number
    5
    10
    Gait disturbance
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 50 (4.00%)
         occurrences all number
    1
    2
    Fatigue
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Asthenia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Crying
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Discomfort
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    9
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 51 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    0
    3
    Reproductive system and breast disorders
    Spontaneous penile erection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 50 (0.00%)
         occurrences all number
    3
    0
    Nasal congestion
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 50 (4.00%)
         occurrences all number
    1
    2
    Rhinorrhoea
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 50 (2.00%)
         occurrences all number
    2
    1
    Choking
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Dysphonia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Hypoxia
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    3
    Increased bronchial secretion
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Lower respiratory tract congestion
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Nasal flaring
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Respiratory disorder
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Increased upper airway secretion
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 50 (4.00%)
         occurrences all number
    3
    2
    Irritability
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 50 (4.00%)
         occurrences all number
    2
    2
    Anxiety
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Sleep disorder
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Attention-seeking behaviour
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Bruxism
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Inappropriate affect
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Middle insomnia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Mood altered
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Nervousness
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Restlessness
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Stereotypy
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Body temperature increased
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    3
    0
    Blood urea increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Influenza virus test positive
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    2
    Platelet count decreased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Urine output decreased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Anticonvulsant drug level decreased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Incorrect dose administered
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    3
    0
    Fall
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    3
    Lip injury
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Sedation complication
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Thermal burn
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Tachycardia paroxysmal
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    8 / 51 (15.69%)
    18 / 50 (36.00%)
         occurrences all number
    8
    20
    Seizure
         subjects affected / exposed
    9 / 51 (17.65%)
    7 / 50 (14.00%)
         occurrences all number
    12
    8
    Sedation
         subjects affected / exposed
    2 / 51 (3.92%)
    3 / 50 (6.00%)
         occurrences all number
    2
    3
    Lethargy
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 50 (4.00%)
         occurrences all number
    2
    2
    Hyperaesthesia
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Hypersomnia
         subjects affected / exposed
    0 / 51 (0.00%)
    2 / 50 (4.00%)
         occurrences all number
    0
    2
    Balance disorder
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Circadian rhythm sleep disorder
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Drooling
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Dyskinesia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Hypotonia
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Poor quality sleep
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Unresponsive to stimuli
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    2
    2
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Lacrimation decreased
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Ocular hyperaemia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    10 / 51 (19.61%)
    5 / 50 (10.00%)
         occurrences all number
    12
    6
    Constipation
         subjects affected / exposed
    3 / 51 (5.88%)
    3 / 50 (6.00%)
         occurrences all number
    3
    3
    Diarrhoea
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 50 (2.00%)
         occurrences all number
    5
    1
    Salivary hypersecretion
         subjects affected / exposed
    1 / 51 (1.96%)
    3 / 50 (6.00%)
         occurrences all number
    1
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 50 (0.00%)
         occurrences all number
    3
    0
    Abdominal pain
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Abdominal discomfort
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Dental caries
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Faecaloma
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Faeces soft
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    4 / 51 (7.84%)
    3 / 50 (6.00%)
         occurrences all number
    4
    3
    Alopecia
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Blister
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Psoriasis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Polyuria
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 51 (5.88%)
    5 / 50 (10.00%)
         occurrences all number
    3
    6
    Rhinitis
         subjects affected / exposed
    4 / 51 (7.84%)
    2 / 50 (4.00%)
         occurrences all number
    5
    4
    Ear infection
         subjects affected / exposed
    3 / 51 (5.88%)
    2 / 50 (4.00%)
         occurrences all number
    3
    2
    Nasopharyngitis
         subjects affected / exposed
    5 / 51 (9.80%)
    0 / 50 (0.00%)
         occurrences all number
    5
    0
    Respiratory tract infection viral
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 50 (2.00%)
         occurrences all number
    3
    1
    Urinary tract infection
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 50 (2.00%)
         occurrences all number
    3
    2
    Gastrointestinal viral infection
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 50 (2.00%)
         occurrences all number
    2
    1
    Influenza
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 50 (4.00%)
         occurrences all number
    1
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Sinusitis
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    Varicella
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 50 (0.00%)
         occurrences all number
    3
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 50 (2.00%)
         occurrences all number
    1
    1
    Anal fungal infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 51 (0.00%)
    2 / 50 (4.00%)
         occurrences all number
    0
    2
    Conjunctivitis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Otitis media
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Roseola
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Viral infection
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Abnormal weight gain
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Decreased appetite
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Dehydration
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Hypophagia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0
    Zinc deficiency
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 50 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 May 2019
    Allowed for an increase in patient enrolment from N=70 to N=100 and for use of concomitant Epidiolex® during the double-blind phase if it was accompanied by a prescription. This amendment also removed the option for a capsule formulation and replaced two open-label study drug pharmacokinetic tests without time parameters to testing to be done 1-5 hours post dose. Updates to investigational product dose modifications clarified minimal dosing and alternative dosing paradigms that would need to be discussed with the medical monitor. To help address any tolerability issues, there was an increase in the number of phone follow-up calls during both double-blind titration and the open-label transition periods. Background information was updated to align with the current Investigator’s Brochure (05-Dec-2018) with no new safety concerns noted. Patients with neurosteroids ALLO-S ≥ 6 ng/mL would be excluded from trial enrolment. Changes to inclusion criteria related to genetic testing information was clarified. An interim analysis was added and select secondary endpoints were updated.
    26 May 2020
    Minor changes involving grammar, wordsmithing, punctuation, and other editorial changes have been made throughout the document. Revised: Prior to unblinding or immediately following, the sponsor’s Medical Monitor must be contacted, Primary Efficacy Endpoint, Key Secondary Efficacy Endpoints, Secondary Efficacy Endpoints (Seizure control), Secondary Efficacy Endpoints (Behavioral/Neuropsychiatric), Exploratory Endpoints and Open-Label Phase Endpoints. Updated The Per-Protocol (PP) population definition to include all ITT subjects who received study drug for at least 6 weeks, provided at least 5 weeks of post-baseline seizure data, and without major protocol violations (defined prior to database lock). Revised: To examine the effect of GNX compared to PBO among subjects with low Allo-S levels. Added: The following subgroup summarizations of the primary efficacy parameter are planned as outlined in the SAP: Allo-S levels [(low (≤2.5 nanograms per milliliter [ng/mL]), middle (> 2.5 ng/mL and < 6.0 ng/mL) or high (≥ 6.0 ng/mL)]; Safety assessments include: AEs, Clinical laboratory tests, Vital signs including temperature, blood pressure, pulse rate, and weight, 12-lead ECG, Physical, neurological and developmental examinations, Tanner staging (OL phase only), Concomitant AED levels (If available); and Key Secondary Efficacy Endpoints. Revised: Subjects that fall below 80% compliance at 2 consecutive visits during the double-blind phase will not be included in the per-protocol population; The clinical research associate (CRA)/study monitor will review all data in accordance with the clinical monitoring plan. If the data are unclear or contradictory to source data, queries are sent for corrections or verification of data; The CRA/study monitor will verify the contents of the eDiary data in accordance with the clinical monitoring plan.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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