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   44334   clinical trials with a EudraCT protocol, of which   7366   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:
    A Two-Part Study of ZX008 in Children and Adults with Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized, Double-blind, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as Adjunctive Therapy for Seizures in Children and Adults with LGS, Followed by Part 2: An Open-label Extension to Assess Long-Term Safety of ZX008 in Children and Adults with LGS

    Summary
    EudraCT number
    2017-002628-26
    Trial protocol
    BE   DE   ES   AT   DK   GB   IT   SE   NL   FR   PL  
    Global end of trial date
    23 May 2024

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Jan 2025
    First version publication date
    05 Jan 2025
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    ZX008-1601
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03355209
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Zogenix International Limited A wholly owned subsidiary of UCB Biosciences, Inc.
    Sponsor organisation address
    4000 Paramount Pkwy, Suite 200, Morrisville, United States, NC 27560
    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
    25 Jun 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 May 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    23 May 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of Part 1 is the primary objective of the entire study. The primary objective of Part 1 is: To evaluate the effect of ZX008 0.8 mg/kg/day versus placebo as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS) based on the change in frequency of seizures that result in drops between baseline and the combined Titration and Maintenance Periods (T+M) The primary objective of Part 2 is to assess the long-term safety and tolerability of ZX008 in children and adults with LGS with regard to AEs, laboratory parameters, physical examination, neurological examination, Tanner Staging, cognition (BRIEF), vital signs (blood pressure, heart rate (HR), temperature, and respiratory rate), electrocardiograms (ECG), echocardiograms (ECHO), body weight, and body mass index (BMI).
    Protection of trial subjects
    During the conduct of the study all participants were closely monitored
    Background therapy
    Background therapy as permitted in the protocol
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    27 Nov 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    72 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Mexico: 3
    Country: Number of subjects enrolled
    Spain: 25
    Country: Number of subjects enrolled
    Italy: 19
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Japan: 33
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    United States: 122
    Worldwide total number of subjects
    296
    EEA total number of subjects
    122
    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)
    117
    Adolescents (12-17 years)
    87
    Adults (18-64 years)
    92
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study started to enroll participants in November 2017 and concluded in May 2024. Cohort A included participants enrolled at sites in North America, Europe, and Australia. Cohort B included participants enrolled at sites in Japan only.

    Pre-assignment
    Screening details
    The Participant Flow refers to the All Enrolled Participants Set for Part 1 and OLE Safety Population for Part 2 of the study. As planned, Part 2 summaries were presented by the participant's Part 1 treatment groups (placebo, ZX008 0.2 mg/kg/day, ZX008 0.8 mg/kg/day).

    Period 1
    Period 1 title
    Part 1: Double-Blind 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
    Cohort A: Placebo
    Arm description
    Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received matching placebo at pre-specified time-points.

    Arm title
    Cohort A: ZX008 0.2 mg/kg/day
    Arm description
    Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort A: ZX008 0.8 mg/kg/day
    Arm description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort B: Placebo
    Arm description
    Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received matching placebo at pre-specified time-points.

    Arm title
    Cohort B: ZX008 0.2 mg/kg/day
    Arm description
    Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort B: ZX008 0.8 mg/kg/day
    Arm description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Number of subjects in period 1
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Started
    87
    89
    87
    11
    11
    11
    Completed
    86
    83
    81
    11
    10
    11
    Not completed
    1
    6
    6
    0
    1
    0
         Adverse event, serious fatal
    -
    -
    1
    -
    -
    -
         Consent withdrawn by subject
    1
    1
    1
    -
    -
    -
         Physician decision
    -
    1
    -
    -
    -
    -
         Adverse event, non-fatal
    -
    4
    4
    -
    1
    -
    Period 2
    Period 2 title
    Part 2:Open-Label Extension (OLE) Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A: Placebo
    Arm description
    Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Placebo

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort A: ZX008 0.2 mg/kg/day
    Arm description
    Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort A: ZX008 0.8 mg/kg/day
    Arm description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort B: Placebo
    Arm description
    Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Placebo

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort B: ZX008 0.2 mg/kg/day
    Arm description
    Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Arm title
    Cohort B: ZX008 0.8 mg/kg/day
    Arm description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Arm type
    Experimental

    Investigational medicinal product name
    Fenfluramine hydrochloride
    Investigational medicinal product code
    ZX008
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ZX008 at pre-specified time-points.

    Number of subjects in period 2 [1]
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Started
    86
    83
    78
    11
    10
    11
    Completed
    61
    51
    46
    5
    1
    5
    Not completed
    25
    32
    32
    6
    9
    6
         Adverse event, serious fatal
    -
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    6
    5
    4
    -
    2
    -
         Physician decision
    -
    -
    -
    1
    -
    1
         Rollover into ZX008-1900
    1
    -
    2
    -
    -
    -
         Switching to commercial ZX008
    -
    -
    -
    5
    6
    3
         Adverse event, non-fatal
    5
    5
    3
    -
    1
    1
         Lack of efficacy
    13
    21
    23
    -
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 3 participants completed Part 1 but did not receive Part 2 study treatment. Reason for withdrawal after completing Part 1 but not Entering Part 2 was AE/AE/Withdrawal by Subject.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort B: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day Total
    Number of subjects
    87 89 87 11 11 11 296
    Age Categorical
    Units: participants
        2 - < 12 years
    32 41 37 2 3 2 117
        12 - < 18 years
    29 23 25 5 2 3 87
        18 - 35 years
    26 25 25 4 6 6 92
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    14.4 ( 7.71 ) 13.4 ( 7.79 ) 13.4 ( 7.28 ) 18.5 ( 7.78 ) 20.1 ( 7.79 ) 18.5 ( 7.94 ) -
    Sex: Female, Male
    Units: participants
        Female
    41 43 33 5 2 2 126
        Male
    46 46 54 6 9 9 170

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Cohort A: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort B: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
    Reporting group title
    Cohort A: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort A: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Cohort B: Placebo
    Reporting group description
    Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.2 mg/kg/day
    Reporting group description
    Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Cohort B: ZX008 0.8 mg/kg/day
    Reporting group description
    Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Subject analysis set title
    Part 2: Cohort A- Overall
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.

    Subject analysis set title
    Part 2: Cohort B- Overall
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Subject analysis set title
    Part 2: Cohort A- Overall
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.

    Subject analysis set title
    Part 2: Cohort B- Overall
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Subject analysis set title
    Part 2: Cohort A- Overall
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.

    Subject analysis set title
    Part 2: Cohort A- Overall
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.

    Subject analysis set title
    Part 2: Cohort B- Overall
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Primary: Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC-confirmed) in the combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/day group compared to the placebo group

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC-confirmed) in the combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/day group compared to the placebo group [1]
    End point description
    Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The Modified Intent-to-Treat (mITT) Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Primary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 'Cohort A: ZX008 0.2 mg/kg/day' and 'Cohort B: ZX008 0.2 mg/kg/day' arms which was part of baseline period were not required for the primary endpoint assessment. Therefore, no data was reported for this arm.
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    87
    11
    11
    Units: percent change
        median (full range (min-max))
    -7.59 (-100.0 to 557.1)
    -26.49 (-95.2 to 402.1)
    -17.89 (-97.3 to 61.8)
    -34.52 (-69.4 to 45.5)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects included in analysis
    174
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.0008
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Median Difference (A-P)
    Point estimate
    -19.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -31.02
         upper limit
    -8.74
    Notes
    [2] - Median Difference was calculated using Hodges-Lehmann (HL) method.

    Primary: Part 2: Percentage of participants with treatment-emergent adverse events (TEAEs)

    Close Top of page
    End point title
    Part 2: Percentage of participants with treatment-emergent adverse events (TEAEs) [3]
    End point description
    An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE.
    End point type
    Primary
    End point timeframe
    From Part 2 Baseline until end of the OLE Period (up to 72 months)
    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
    Part 2: Cohort A- Overall Part 2: Cohort B- Overall
    Number of subjects analysed
    247
    32
    Units: percentage of participants
        number (not applicable)
    83.0
    96.9
    No statistical analyses for this end point

    Primary: Part 2: Percentage of participants with Serious TEAEs

    Close Top of page
    End point title
    Part 2: Percentage of participants with Serious TEAEs [4]
    End point description
    A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant. The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE.
    End point type
    Primary
    End point timeframe
    From Part 2 Baseline until end of the OLE Period (up to 72 months)
    Notes
    [4] - 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
    Part 2: Cohort A- Overall Part 2: Cohort B- Overall
    Number of subjects analysed
    247
    32
    Units: percentage of participants
        number (not applicable)
    16.6
    18.8
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieve a >=50% reduction from Baseline in the frequency of seizures that result in drops comparing the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieve a >=50% reduction from Baseline in the frequency of seizures that result in drops comparing the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a >=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
        number (not applicable)
    10.3
    28.1
    25.3
    9.1
    36.4
    36.4
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects included in analysis
    174
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.015
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.23
         upper limit
    6.7
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.2 mg/kg/day
    Number of subjects included in analysis
    176
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0051
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    3.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.43
         upper limit
    7.59

    Secondary: Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/day group compared to the placebo group

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/day group compared to the placebo group [5]
    End point description
    Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for the 'Cohort A: ZX008 0.8 mg/kg/day' and 'Cohort B: ZX008 0.8 mg/kg/day' arms was reported in primary endpoint therefore, these arms which was part of baseline period were not required for the secondary endpoint assessment. Hence, no data was reported for these arms.
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day
    Number of subjects analysed
    87
    89
    11
    11
    Units: percent change
        median (full range (min-max))
    -7.59 (-100.0 to 557.1)
    -14.16 (-100.0 to 3307.3)
    -17.89 (-97.3 to 61.8)
    -14.12 (-95.6 to 66.4)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.2 mg/kg/day
    Number of subjects included in analysis
    176
    Analysis specification
    Pre-specified
    Analysis type
    superiority [6]
    P-value
    = 0.146
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Median Difference (A-P)
    Point estimate
    -10.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.99
         upper limit
    3.99
    Notes
    [6] - Median Difference was calculated using HL method.

    Secondary: Part 1: Percentage of participants who achieve improvement (minimally, much or very much improved) in the CGI-I scale as assessed by Principal Investigator comparing ZX008 0.8 and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieve improvement (minimally, much or very much improved) in the CGI-I scale as assessed by Principal Investigator comparing ZX008 0.8 and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Clinical Global Impression – Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    At Day 99 (Visit 12)
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    80
    85
    80
    11
    11
    11
    Units: percentage of participants
        number (not applicable)
    33.8
    44.7
    48.8
    9.1
    45.5
    72.7
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Visit 12
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0567
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.98
         upper limit
    3.52
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Visit 12
    Comparison groups
    Cohort A: Placebo v Cohort A: ZX008 0.2 mg/kg/day
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1565
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    2.97

    Secondary: Part 1: Percent change from Baseline in the frequency of all countable motor seizures in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of all countable motor seizures in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -8.43 (-80.8 to 497.8)
    -11.75 (-100.0 to 3307.3)
    -26.28 (-91.9 to 402.1)
    -17.89 (-97.3 to 61.8)
    -14.12 (-95.6 to 174.1)
    -34.04 (-69.4 to 45.5)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in frequency of all seizures that typically result in drops in T+M, whether ESC-confirmed as drop or not in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in frequency of all seizures that typically result in drops in T+M, whether ESC-confirmed as drop or not in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient’s position at the time of the seizure. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -8.43 (-100.0 to 557.1)
    -11.75 (-100.0 to 3307.3)
    -26.28 (-95.2 to 402.1)
    -17.89 (-97.3 to 61.8)
    -14.12 (-95.6 to 66.4)
    -34.04 (-69.4 to 45.5)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in the frequency of all countable seizures (motor and non-motor) in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of all countable seizures (motor and non-motor) in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -9.40 (-85.4 to 497.8)
    -23.55 (-100.0 to 882.1)
    -21.70 (-91.9 to 224.9)
    -17.69 (-97.2 to 61.8)
    -20.41 (-87.1 to 826.2)
    -13.85 (-64.9 to 63.8)
    No statistical analyses for this end point

    Secondary: Part 1: Change from Baseline in the frequency of all countable non-motor seizures in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Change from Baseline in the frequency of all countable non-motor seizures in T+M in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: seizure frequency per 28 days
        median (full range (min-max))
    0.00 (-338.3 to 364.3)
    0.00 (-418.7 to 675.8)
    0.00 (-364.0 to 2952.7)
    -7.16 (-30.3 to 13.1)
    0.00 (-32.3 to 104.8)
    0.00 (-61.6 to 209.5)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in the frequency of seizures that typically result in drops in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of seizures that typically result in drops in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The mITT Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    88
    86
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -9.37 (-100.0 to 516.7)
    -17.30 (-100.0 to 964.0)
    -26.30 (-100.0 to 643.3)
    -18.18 (-99.4 to 66.7)
    -12.88 (-100.0 to 239.4)
    -46.88 (-77.8 to 52.2)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC confirmed) between Baseline and the Maintenance Period

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of seizures that result in drops (ESC confirmed) between Baseline and the Maintenance Period
    End point description
    The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    88
    86
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -7.28 (-100.0 to 516.7)
    -18.63 (-100.0 to 964.0)
    -27.16 (-100.0 to 643.3)
    -18.18 (-99.4 to 66.7)
    -12.88 (-100.0 to 239.4)
    -45.07 (-77.8 to 52.2)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in the frequency of all countable motor seizures in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of all countable motor seizures in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    88
    86
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -10.21 (-81.1 to 439.8)
    -17.30 (-100.0 to 964.0)
    -28.33 (-100.0 to 643.3)
    -18.18 (-99.4 to 66.7)
    -12.88 (-100.0 to 472.7)
    -46.88 (-77.8 to 52.2)
    No statistical analyses for this end point

    Secondary: Part 1: Change from Baseline in the frequency of all countable non-motor seizures in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Change from Baseline in the frequency of all countable non-motor seizures in the Maintenance Period in the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    88
    86
    11
    11
    11
    Units: seizure frequency per 28 days
        median (full range (min-max))
    -0.04 (-340.6 to 362.3)
    -0.13 (-442.3 to 588.1)
    0.00 (-368.3 to 3219.3)
    -4.00 (-30.7 to 15.3)
    0.00 (-37.2 to 192.0)
    0.00 (-86.8 to 250.7)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in the frequency of all countable seizures (motor and non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in the frequency of all countable seizures (motor and non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    88
    86
    11
    11
    11
    Units: percent change
        median (full range (min-max))
    -9.49 (-85.7 to 439.8)
    -27.63 (-100.0 to 211.1)
    -23.34 (-100.0 to 254.5)
    -18.18 (-99.5 to 66.7)
    -20.33 (-95.7 to 1626.7)
    -17.68 (-72.3 to 80.5)
    No statistical analyses for this end point

    Secondary: Part 1: Percent change from Baseline in frequency of countable seizures that do not result in drops (ESC Confirmed)

    Close Top of page
    End point title
    Part 1: Percent change from Baseline in frequency of countable seizures that do not result in drops (ESC Confirmed)
    End point description
    Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    70
    73
    64
    8
    7
    9
    Units: percent change
        median (full range (min-max))
    -26.92 (-100.0 to 5070.3)
    -31.32 (-100.0 to 571.8)
    -22.68 (-100.0 to 481.3)
    -23.38 (-96.9 to 657.1)
    0.27 (-32.3 to 2915.4)
    -22.99 (-85.7 to 138.8)
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline (ie <=0% reduction), or >0, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in seizures that result in drops

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline (ie <=0% reduction), or >0, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in seizures that result in drops
    End point description
    The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=87,89,87,11,11,11)
    37.9
    34.8
    21.8
    36.4
    27.3
    9.1
        > 0% reduction (T+M) (n=87,89,87,11,11,11)
    62.1
    65.2
    78.2
    63.6
    72.7
    90.9
        >= 25% reduction (T+M) (n=87,89,87,11,11,11)
    31.0
    47.2
    51.7
    36.4
    36.4
    63.6
        >= 50% reduction (T+M) (n=87,89,87,11,11,11)
    10.3
    28.1
    25.3
    9.1
    36.4
    36.4
        >= 75% reduction (T+M) (n=87,89,87,11,11,11)
    4.6
    10.1
    8.0
    9.1
    9.1
    0
        100% reduction (T+M) (n=87,89,87,11,11,11)
    1.1
    1.1
    0
    0
    0
    0
        Near Seizure free (T+M) (n=87,89,87,11,11,11)
    1.1
    2.2
    1.1
    0
    0
    0
        Worsening or No Change (M) (n=87, 88,86,11,11,11)
    40.2
    35.2
    20.9
    36.4
    27.3
    9.1
        > 0% reduction (M) (n=87, 88,86,11,11,11)
    59.8
    64.8
    79.1
    63.6
    72.7
    90.9
        >= 25% reduction (M) (n=87, 88,86,11,11,11)
    33.3
    46.6
    53.5
    36.4
    36.4
    72.7
        >= 50% reduction (M) (n=87, 88,86,11,11,11)
    12.6
    31.8
    31.4
    9.1
    36.4
    36.4
        >= 75% reduction (M) (n=87, 88,86,11,11,11)
    3.4
    11.4
    14.0
    9.1
    9.1
    9.1
        100% reduction (M) (n=87, 88,86,11,11,11)
    1.1
    3.4
    2.3
    0
    9.1
    0
        Near Seizure free (M) (n=87, 88,86,11,11,11)
    1.1
    4.5
    2.3
    9.1
    9.1
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in seizures that typically results in drops

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in seizures that typically results in drops
    End point description
    Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=87,89,87,11,11,11)
    35.6
    36.0
    20.7
    36.4
    27.3
    9.1
        > 0% reduction (T+M) (n=87,89,87,11,11,11)
    64.4
    64.0
    79.3
    63.6
    72.7
    90.9
        >= 25% reduction (T+M) (n=87,89,87,11,11,11)
    31.0
    46.1
    50.6
    36.4
    36.4
    63.6
        >= 50% reduction (T+M) (n=87,89,87,11,11,11)
    9.2
    27.0
    26.4
    9.1
    36.4
    36.4
        >= 75% reduction (T+M) (n=87,89,87,11,11,11)
    3.4
    9.0
    8.0
    9.1
    9.1
    0
        100% reduction (T+M) (n=87,89,87,11,11,11)
    1.1
    1.1
    0
    0
    0
    0
        Near Seizure free (T+M) (n=87,89,87,11,11,11)
    1.1
    1.1
    1.1
    0
    0
    0
        Worsening or No Change (M) (n=87,88,86,11,11,11)
    37.9
    37.5
    19.8
    36.4
    27.3
    9.1
        > 0% reduction (M) (n=87,88,86,11,11,11)
    62.1
    62.5
    80.2
    63.6
    72.7
    90.9
        >= 25% reduction (M) (n=87,88,86,11,11,11)
    33.3
    45.5
    52.3
    36.4
    36.4
    72.7
        >= 50% reduction (M) (n=87,88,86,11,11,11)
    10.3
    30.7
    31.4
    9.1
    36.4
    36.4
        >= 75% reduction (M) (n=87,88,86,11,11,11)
    2.3
    10.2
    12.8
    9.1
    9.1
    9.1
        100% reduction (M) (n=87,88,86,11,11,11)
    1.1
    2.3
    2.3
    0
    9.1
    0
        Near Seizure free (M) (n=87,88,86,11,11,11)
    1.1
    2.3
    2.3
    9.1
    9.1
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable motor seizures

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable motor seizures
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=87,89,87,11,11,11)
    34.5
    38.2
    20.7
    36.4
    27.3
    9.1
        > 0% reduction (T+M) (n=87,89,87,11,11,11)
    65.5
    61.8
    79.3
    63.6
    72.7
    90.9
        >= 25% reduction (T+M) (n=87,89,87,11,11,11)
    33.3
    44.9
    50.6
    36.4
    36.4
    63.6
        >= 50% reduction (T+M) (n=87,89,87,11,11,11)
    9.2
    24.7
    25.3
    9.1
    36.4
    36.4
        >= 75% reduction (T+M) (n=87,89,87,11,11,11)
    2.3
    9.0
    6.9
    9.1
    9.1
    0
        100% reduction (T+M) (n=87,89,87,11,11,11)
    0
    1.1
    0
    0
    0
    0
        Near Seizure free (T+M) (n=87,89,87,11,11,11)
    0
    1.1
    0
    0
    0
    0
        Worsening or No Change (M) (n=87,88,86,11,11,11)
    36.8
    38.6
    18.6
    36.4
    27.3
    9.1
        > 0% reduction (M) (n=87,88,86,11,11,11)
    63.2
    61.4
    81.4
    63.6
    72.7
    90.9
        >= 25% reduction (M) (n=87,88,86,11,11,11)
    34.5
    45.5
    53.5
    36.4
    36.4
    72.7
        >= 50% reduction (M) (n=87,88,86,11,11,11)
    10.3
    28.4
    26.7
    9.1
    36.4
    36.4
        >= 75% reduction (M) (n=87,88,86,11,11,11)
    1.1
    11.4
    10.5
    9.1
    9.1
    9.1
        100% reduction (M) (n=87,88,86,11,11,11)
    0
    2.3
    1.2
    0
    9.1
    0
        Near Seizure free (M) (n=87,88,86,11,11,11)
    0
    2.3
    1.2
    9.1
    9.1
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in countable motor seizures that do not result in drops

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in countable motor seizures that do not result in drops
    End point description
    Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    70
    73
    64
    8
    7
    9
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=70,73,64,8,7,9)
    35.7
    34.2
    34.4
    25.0
    57.1
    44.4
        > 0% reduction (T+M) (n=70,73,64,8,7,9)
    64.3
    65.8
    65.6
    75.0
    42.9
    55.6
        >= 25% reduction (T+M) (n=70,73,64,8,7,9)
    51.4
    53.4
    46.9
    50.0
    14.3
    44.4
        >= 50% reduction (T+M) (n=70,73,64,8,7,9)
    30.0
    43.8
    32.8
    25.0
    0
    22.2
        >= 75% reduction (T+M) (n=70,73,64,8,7,9)
    12.9
    26.0
    12.5
    12.5
    0
    11.1
        100% reduction (T+M) (n=70,73,64,8,7,9)
    2.9
    5.5
    4.7
    0
    0
    0
        Near Seizure free (T+M) (n=70,73,64,8,7,9)
    2.9
    9.6
    7.8
    0
    0
    0
        Worsening or No Change (M) (n=70,72,63,8,7,9)
    31.4
    33.3
    34.9
    25.0
    57.1
    44.4
        > 0% reduction (M) (n=70,72,63,8,7,9)
    68.6
    66.7
    65.1
    75.0
    42.9
    55.6
        >= 25% reduction (M) (n=70,72,63,8,7,9)
    54.3
    56.9
    49.2
    50.0
    14.3
    44.4
        >= 50% reduction (M) (n=70,72,63,8,7,9)
    31.4
    44.4
    33.3
    25.0
    0
    22.2
        >= 75% reduction (M) (n=70,72,63,8,7,9)
    17.1
    29.2
    17.5
    12.5
    0
    11.1
        100% reduction (M) (n=70,72,63,8,7,9)
    5.7
    9.7
    6.3
    12.5
    0
    0
        Near Seizure free (M) (n=70,72,63,8,7,9)
    7.1
    13.9
    9.5
    12.5
    0
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline (ie <= 0% reduction), or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable seizures

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline (ie <= 0% reduction), or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable seizures
    End point description
    Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=87,89,87,11,11,11)
    36.8
    32.6
    28.7
    27.3
    27.3
    36.4
        > 0% reduction (T+M) (n=87,89,87,11,11,11)
    63.2
    67.4
    71.3
    72.7
    72.7
    63.6
        >= 25% reduction (T+M) (n=87,89,87,11,11,11)
    35.6
    48.3
    46.0
    27.3
    27.3
    45.5
        >= 50% reduction (T+M) (n=87,89,87,11,11,11)
    11.5
    22.5
    20.7
    9.1
    27.3
    27.3
        >= 75% reduction (T+M) (n=87,89,87,11,11,11)
    3.4
    6.7
    4.6
    9.1
    9.1
    0
        100% reduction (T+M) (n=87,89,87,11,11,11)
    0
    1.1
    0
    0
    0
    0
        Near Seizure free (T+M) (n=87,89,87,11,11,11)
    0
    1.1
    0
    0
    0
    0
        Worsening or No Change (M) (n=87,88,86,11,11,11)
    34.5
    33.0
    27.9
    27.3
    27.3
    27.3
        > 0% reduction (M) (n=87,88,86,11,11,11)
    65.5
    67.0
    72.1
    72.7
    72.7
    72.7
        >= 25% reduction (M) (n=87,88,86,11,11,11)
    34.5
    51.1
    47.7
    27.3
    27.3
    45.5
        >= 50% reduction (M) (n=87,88,86,11,11,11)
    13.8
    28.4
    24.4
    9.1
    27.3
    27.3
        >= 75% reduction (M) (n=87,88,86,11,11,11)
    3.4
    9.1
    7.0
    9.1
    9.1
    0
        100% reduction (M) (n=87,88,86,11,11,11)
    0
    1.1
    1.2
    0
    0
    0
        Near Seizure free (M) (n=87,88,86,11,11,11)
    0
    1.1
    1.2
    9.1
    0
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable non-motor seizures

    Close Top of page
    End point title
    Part 1: Percentage of participants who achieved a worsening from Baseline, or >0%, >=25%, >=50%, >=75%, 100% reduction, and “near seizure freedom” between Baseline and T+M, and Baseline and M, in all countable non-motor seizures
    End point description
    Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    63
    64
    57
    8
    7
    8
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change (T+M) (n=63,64,57,8,7,8)
    33.3
    34.4
    36.8
    25.0
    57.1
    37.5
        > 0% reduction (T+M) (n=63,64,57,8,7,8)
    66.7
    65.6
    63.2
    75.0
    42.9
    62.5
        >= 25% reduction (T+M) (n=63,64,57,8,7,8)
    52.4
    56.3
    43.9
    50.0
    14.3
    37.5
        >= 50% reduction (T+M) (n=63,64,57,8,7,8)
    30.2
    48.4
    35.1
    25.0
    0
    25.0
        >= 75% reduction (T+M) (n=63,64,57,8,7,8)
    14.3
    32.8
    12.3
    12.5
    0
    0
        100% reduction (T+M) (n=63,64,57,8,7,8)
    3.2
    6.3
    3.5
    0
    0
    0
        Near Seizure free (T+M) (n=63,64,57,8,7,8)
    3.2
    14.1
    5.3
    0
    0
    0
        Worsening or No Change (M) (n=63,63,56,8,7,8)
    30.2
    30.2
    33.9
    12.5
    57.1
    37.5
        > 0% reduction (M) (n=63,63,56,8,7,8)
    69.8
    69.8
    66.1
    87.5
    42.9
    62.5
        >= 25% reduction (M) (n=63,63,56,8,7,8)
    54.0
    60.3
    48.2
    50.0
    14.3
    37.5
        >= 50% reduction (M) (n=63,63,56,8,7,8)
    34.9
    49.2
    33.9
    25.0
    0
    37.5
        >= 75% reduction (M) (n=63,63,56,8,7,8)
    17.5
    31.7
    17.9
    12.5
    0
    0
        100% reduction (M) (n=63,63,56,8,7,8)
    6.3
    9.5
    8.9
    12.5
    0
    0
        Near Seizure free (M) (n=63,63,56,8,7,8)
    7.9
    15.9
    10.7
    12.5
    0
    0
    No statistical analyses for this end point

    Secondary: Part 1: Change from Baseline in number of seizure-free days during T+M and M Period

    Close Top of page
    End point title
    Part 1: Change from Baseline in number of seizure-free days during T+M and M Period
    End point description
    A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure–free days was calculated per 28 days for Baseline and for T+M. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, 'n' included those participants who were evaluable for specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: seizure free days per 28 days
    median (full range (min-max))
        T+M Period (n=87,89,87,11,11,11)
    0.27 (-5.0 to 16.0)
    0.00 (-9.0 to 16.8)
    0.29 (-6.1 to 20.0)
    0.00 (-2.2 to 23.6)
    0.38 (-2.3 to 22.0)
    6.65 (-2.4 to 8.5)
        M Period (n=87,88,86,11,11,11)
    0.31 (-5.4 to 15.7)
    0.00 (-4.1 to 18.2)
    0.16 (-7.4 to 21.7)
    -0.65 (-2.7 to 24.7)
    0.33 (-7.3 to 26.0)
    7.72 (-2.3 to 10.3)
    No statistical analyses for this end point

    Secondary: Part 1: Clinical Global Impression – Improvement as assessed by the Parent/Caregiver

    Close Top of page
    End point title
    Part 1: Clinical Global Impression – Improvement as assessed by the Parent/Caregiver
    End point description
    CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    At Days (D) 15, 43, 71, and 99
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    85
    85
    81
    11
    11
    11
    Units: percentage of participants
    number (not applicable)
        1=Very much improved (D15) (n=85,85,81,11,10,11)
    2.4
    5.9
    9.9
    9.1
    10.0
    9.1
        2=Much improved (D15) (n=85,85,81,11,10,11)
    4.7
    15.3
    21.0
    18.2
    10.0
    18.2
        3=Minimally improved (D15) (n=85,85,81,11,10,11)
    31.8
    27.1
    39.5
    9.1
    30.0
    27.3
        4=No Change (D15) (n=85,85,81,11,10,11)
    51.8
    42.4
    18.5
    63.6
    30.0
    27.3
        5=Minimally worse (D15) (n=85,85,81,11,10,11)
    4.7
    5.9
    7.4
    0
    20.0
    18.2
        6=Much worse (D15) (n=85,85,81,11,10,11)
    4.7
    3.5
    2.5
    0
    0
    0
        7=Very much worse (D15) (n=85,85,81,11,10,11)
    0
    0
    1.2
    0
    0
    0
        1=Very much improved (D43) (n=85,82,80,11,9,10)
    1.2
    7.3
    13.8
    9.1
    0
    10.0
        2=Much improved (D43) (n=85,82,80,11,9,10)
    9.4
    19.5
    25.0
    0
    22.2
    40.0
        3=Minimally improved (D43) (n=85,82,80,11,9,10)
    20.0
    18.3
    33.8
    18.2
    44.4
    30.0
        4=No Change (D43) (n=85,82,80,11,9,10)
    60.0
    39.0
    17.5
    63.6
    33.3
    0
        5=Minimally worse (D43) (n=85,82,80,11,9,10)
    5.9
    11.0
    5.0
    9.1
    0
    20.0
        6=Much worse (D43) (n=85,82,80,11,9,10)
    2.4
    4.9
    5.0
    0
    0
    0
        7=Very much worse (D43) (n=85,82,80,11,9,10)
    1.2
    0
    0
    0
    0
    0
        1=Very much improved (D71) (n=82,75,75,11,9,9)
    2.4
    4.0
    10.7
    9.1
    0
    0
        2=Much improved (D71) (n=82,75,75,11,9,9)
    6.1
    20.0
    28.0
    0
    22.2
    11.1
        3=Minimally improved (D71) (n=82,75,75,11,9,9)
    24.4
    16.0
    33.3
    18.2
    22.2
    55.6
        4=No Change (D71) (n=82,75,75,11,9,9)
    53.7
    48.0
    24.0
    63.6
    55.6
    22.2
        5=Minimally worse (D71) (n=82,75,75,11,9,9)
    7.3
    8.0
    1.3
    9.1
    0
    11.1
        6=Much worse (D71) (n=82,75,75,11,9,9)
    6.1
    4.0
    2.7
    0
    0
    0
        7=Very much worse (D71) (n=82,75,75,11,9,9)
    0
    0
    0
    0
    0
    0
        1=Very much improved (D99) (n=81,85,80,11,11,11)
    1.2
    8.2
    10.0
    9.1
    0
    18.2
        2=Much improved (D99) (n=81,85,80,11,11,11)
    3.7
    18.8
    23.8
    0
    18.2
    18.2
        3=Minimally improved (D99) (n=81,85,80,11,11,11)
    32.1
    16.5
    27.5
    18.2
    27.3
    36.4
        4=No Change (D99) (n=81,85,80,11,11,11)
    53.1
    37.6
    27.5
    63.6
    45.5
    27.3
        5=Minimally worse (D99) (n=81,85,80,11,11,11)
    7.4
    8.2
    5.0
    0
    9.1
    0
        6=Much worse (D99) (n=81,85,80,11,11,11)
    2.5
    7.1
    5.0
    9.1
    0
    0
        7=Very much worse (D99) (n=81,85,80,11,11,11)
    0
    3.5
    1.3
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Part 1: Duration of longest interval (days) between seizures that result in drops comparing the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo

    Close Top of page
    End point title
    Part 1: Duration of longest interval (days) between seizures that result in drops comparing the ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    End point description
    The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures. The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: days
        median (full range (min-max))
    5.00 (1.0 to 39.0)
    4.00 (1.0 to 97.0)
    5.00 (1.0 to 89.0)
    4.00 (1.0 to 91.0)
    4.00 (1.0 to 32.0)
    6.00 (2.0 to 16.0)
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants with Serious TEAEs

    Close Top of page
    End point title
    Part 1: Percentage of participants with Serious TEAEs
    End point description
    A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant. The Safety Population included all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 weeks + Taper/Transition (2 weeks)
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
        number (not applicable)
    4.6
    4.5
    11.5
    9.1
    9.1
    0
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants with TEAEs

    Close Top of page
    End point title
    Part 1: Percentage of participants with TEAEs
    End point description
    Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2. The Safety Population included all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 weeks + Taper/Transition (2 weeks)
    End point values
    Cohort A: Placebo Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day Cohort B: Placebo Cohort B: ZX008 0.2 mg/kg/day Cohort B: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    87
    89
    87
    11
    11
    11
    Units: percentage of participants
        number (not applicable)
    80.5
    78.7
    89.7
    72.7
    90.9
    63.6
    No statistical analyses for this end point

    Secondary: Part 1: Maximum observed Plasma concentration of fenfluramine and norfenfluramine determined directly from the concentration time profile [Cmax] at steady state

    Close Top of page
    End point title
    Part 1: Maximum observed Plasma concentration of fenfluramine and norfenfluramine determined directly from the concentration time profile [Cmax] at steady state [7]
    End point description
    Cmax is the maximum plasma concentration determined directly from the concentration time profile. The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
    End point type
    Secondary
    End point timeframe
    At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK endpoints were planned to be reported for ZX008 arms only.
    End point values
    Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    84
    80
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Fenfluramine
    11.9 ( 56.1 )
    44.8 ( 47.0 )
        Norfenfluramine
    9.04 ( 53.4 )
    28.9 ( 52.9 )
    No statistical analyses for this end point

    Secondary: Part 1: Minimum observed plasma concentration of fenfluramine and norfenfluramine at steady state determined directly from the concentration-time profile [Cmin] at steady state

    Close Top of page
    End point title
    Part 1: Minimum observed plasma concentration of fenfluramine and norfenfluramine at steady state determined directly from the concentration-time profile [Cmin] at steady state [8]
    End point description
    Cmin is the minimum plasma concentration determined directly from the concentration-time profile. The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
    End point type
    Secondary
    End point timeframe
    At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK endpoints were planned to be reported for ZX008 arms only.
    End point values
    Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    84
    80
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Fenfluramine
    8.19 ( 75.6 )
    31.8 ( 60.8 )
        Norfenfluramine
    8.23 ( 61.3 )
    26.2 ( 58.9 )
    No statistical analyses for this end point

    Secondary: Part 2: Percent change from Baseline in the frequency all seizures that typically result in drops between Baseline and the OLE Period whether ESC confirmed as drop or not

    Close Top of page
    End point title
    Part 2: Percent change from Baseline in the frequency all seizures that typically result in drops between Baseline and the OLE Period whether ESC confirmed as drop or not
    End point description
    Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient’s position at the time of the seizure. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percent change
        median (full range (min-max))
    -43.78 (-99.0 to 64.2)
    -27.94 (-100.0 to 2625.3)
    No statistical analyses for this end point

    Secondary: Part 1: Area under the concentration-time curve of of fenfluramine and norfenfluramine from time zero to time 24 hours [AUC0-24hours] at steady state

    Close Top of page
    End point title
    Part 1: Area under the concentration-time curve of of fenfluramine and norfenfluramine from time zero to time 24 hours [AUC0-24hours] at steady state [9]
    End point description
    AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours. The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
    End point type
    Secondary
    End point timeframe
    At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK endpoints were planned to be reported for ZX008 arms only.
    End point values
    Cohort A: ZX008 0.2 mg/kg/day Cohort A: ZX008 0.8 mg/kg/day
    Number of subjects analysed
    84
    80
    Units: nanograms*hour per milliliter (ng*h/mL)
    geometric mean (geometric coefficient of variation)
        Fenfluramine
    246 ( 63.0 )
    933 ( 52.1 )
        Norfenfluramine
    209 ( 56.3 )
    667 ( 55.1 )
    No statistical analyses for this end point

    Secondary: Part 2: Percent change from Baseline in the frequency of seizures that result in drops (ESC Confirmed) in OLE Period

    Close Top of page
    End point title
    Part 2: Percent change from Baseline in the frequency of seizures that result in drops (ESC Confirmed) in OLE Period
    End point description
    The frequency of drop seizures during a given interval was derived from the number and type of events recorded in subject electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The Open-Label Extension Modified Intent-To-Treat (mITT) Population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percent change
        median (full range (min-max))
    -43.42 (-99.0 to 64.2)
    -29.53 (-100.0 to 2625.3)
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of seizures that result in drops (ESC confirmed)

    Close Top of page
    End point title
    Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of seizures that result in drops (ESC confirmed)
    End point description
    The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily gneralized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during OLE Period was reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change
    18.8
    31.5
        > 0%
    81.3
    68.5
        >= 25%
    62.5
    55.6
        >= 50%
    43.8
    32.8
        >= 75%
    21.9
    12.4
        100%
    0
    1.2
        Near Seizure free
    0
    1.7
    No statistical analyses for this end point

    Secondary: Part 2: Percent change from Baseline in the frequency of all countable motor seizures in OLE Period

    Close Top of page
    End point title
    Part 2: Percent change from Baseline in the frequency of all countable motor seizures in OLE Period
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percent change
        median (full range (min-max))
    -41.94 (-99.0 to 64.2)
    -28.18 (-100.0 to 2625.3)
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in the frequency of all countable non-motor seizures in OLE Period

    Close Top of page
    End point title
    Part 2: Change from Baseline in the frequency of all countable non-motor seizures in OLE Period
    End point description
    Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: seizure frequency per 28 days
        median (full range (min-max))
    0.00 (-89.4 to 258.9)
    0.00 (-4257.2 to 1774.3)
    No statistical analyses for this end point

    Secondary: Part 2: Percent change from Baseline in the frequency of all countable seizures (ESC confirmed or not) in OLE Period

    Close Top of page
    End point title
    Part 2: Percent change from Baseline in the frequency of all countable seizures (ESC confirmed or not) in OLE Period
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percent change
        median (full range (min-max))
    -28.00 (-99.1 to 83.3)
    -28.83 (-100.0 to 606.1)
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in the frequency of all countable seizures that did not result in drops (ESC confirmed) in OLE Period

    Close Top of page
    End point title
    Part 2: Change from Baseline in the frequency of all countable seizures that did not result in drops (ESC confirmed) in OLE Period
    End point description
    Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: seizure frequency per 28 days
        median (full range (min-max))
    0.00 (-89.4 to 258.9)
    -0.99 (-4482.2 to 1774.3)
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of seizures that typically result in drops

    Close Top of page
    End point title
    Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of seizures that typically result in drops
    End point description
    Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during combined OLE Period were reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change
    21.9
    32.0
        > 0%
    78.1
    68.0
        >= 25%
    65.6
    53.1
        >= 50%
    43.8
    29.9
        >= 75%
    21.9
    11.2
        100%
    0
    0.8
        Near Seizure free
    0
    1.2
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable motor seizures

    Close Top of page
    End point title
    Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable motor seizures
    End point description
    Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during OLE Period was reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change
    21.9
    29.5
        > 0%
    78.1
    70.5
        >= 25%
    62.5
    54.8
        >= 50%
    40.6
    29.9
        >= 75%
    21.9
    9.1
        100%
    0
    0.4
        Near Seizure free
    0
    0.8
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable non-motor seizures

    Close Top of page
    End point title
    Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable non-motor seizures
    End point description
    Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during OLE Period was reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change
    37.5
    24.1
        > 0%
    31.3
    46.1
        >= 25%
    25.0
    41.9
        >= 50%
    18.8
    34.0
        >= 75%
    6.3
    22.8
        100%
    3.1
    4.6
        Near Seizure free
    6.3
    7.5
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable seizures

    Close Top of page
    End point title
    Part 2: Percentage of participants who achieved a worsening from Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% reduction, and “near seizure freedom” from Baseline in frequency of all countable seizures
    End point description
    Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and “near seizure freedom,” (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From OLE Month 1 to Month12, compared to Baseline (Part 1)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: percentage of participants
    number (not applicable)
        Worsening or No Change
    37.5
    30.3
        > 0%
    62.5
    69.7
        >= 25%
    56.3
    53.1
        >= 50%
    28.1
    30.7
        >= 75%
    12.5
    9.1
        100%
    0
    0.4
        Near Seizure free
    0
    0.4
    No statistical analyses for this end point

    Secondary: Part 2: Clinical Global Impression – Improvement as assessed by the Principal Investigator

    Close Top of page
    End point title
    Part 2: Clinical Global Impression – Improvement as assessed by the Principal Investigator
    End point description
    CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. Here, number of participants analyzed included those participants who were evaluable for the assessment. 'n' analyzed included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    237
    Units: percentage of participants
    number (not applicable)
        1=Very much improved (OLE D1) (n=236,32)
    3.1
    2.5
        2=Much improved (OLE D1) (n=236,32)
    18.8
    15.3
        3=Minimally improved (OLE D1) (n=236,32)
    18.8
    25.8
        4=No Change (OLE D1) (n=236,32)
    56.3
    48.3
        5=Minimally worse (OLE D1)(n=236,32)
    3.1
    7.2
        6=Much worse (OLE D1) (n=236,32)
    0
    0.8
        7=Very much worse (OLE D1) (n=236,32)
    0
    0
        1=Very much improved (OLE M1) (n=225,32)
    9.4
    4.4
        2=Much improved (OLE M1) (n=225,32)
    21.9
    20.0
        3=Minimally improved (OLE M1) (n=225,32)
    37.5
    32.4
        4=No Change (OLE M1) (n=225,32)
    31.3
    34.2
        5=Minimally worse (OLE M1) (n=225,32)
    0
    7.6
        6=Much worse (OLE M1) (n=225,32)
    0
    1.3
        7=Very much worse (OLE M1) (n=225,32)
    0
    0
        1=Very much improved (OLE M2) (n=220,31)
    6.5
    5.5
        2=Much improved (OLE M2) (n=220,31)
    19.4
    24.5
        3=Minimally improved (OLE M2) (n=220,31)
    35.5
    34.1
        4=No Change (OLE M2) (n=220,31)
    32.3
    27.7
        5=Minimally worse (OLE M2) (n=220,31)
    6.5
    5.0
        6=Much worse (OLE M2) (n=220,31)
    0
    3.2
        7=Very much worse (OLE M2) (n=220,31)
    0
    0
        1=Very much improved (OLE M3) (n=207,29)
    6.9
    7.2
        2=Much improved (OLE M3) (n=207,29)
    17.2
    25.1
        3=Minimally improved (OLE M3) (n=207,29)
    55.2
    36.2
        4=No Change (OLE M3) (n=207,29)
    20.7
    21.7
        5=Minimally worse (OLE M3) (n=207,29)
    0
    7.2
        6=Much worse (OLE M3) (n=207,29)
    0
    2.4
        7=Very much worse (OLE M3) (n=207,29)
    0
    0
        1=Very much improved (OLE M6) (n=184,29)
    3.4
    8.2
        2=Much improved (OLE M6) (n=184,29)
    27.6
    33.7
        3=Minimally improved (OLE M6) (n=184,29)
    34.5
    31.0
        4=No Change (OLE M6) (n=184,29)
    27.6
    20.1
        5=Minimally worse (OLE M6) (n=184,29)
    6.9
    3.8
        6=Much worse (OLE M6) (n=184,29)
    0
    3.3
        7=Very much worse (OLE M6) (n=184,29)
    0
    0
        1=Very much improved (OLE M9) (n=133,28)
    3.6
    9.0
        2=Much improved (OLE M9) (n=133,28)
    28.6
    37.6
        3=Minimally improved (OLE M9) (n=133,28)
    28.6
    27.1
        4=No Change (OLE M9) (n=133,28)
    35.7
    18.8
        5=Minimally worse (OLE M9) (n=133,28)
    3.6
    6.0
        6=Much worse (OLE M9) (n=133,28)
    0
    1.5
        7=Very much worse (OLE M9) (n=133,28)
    0
    0
        1=Very much improved (OLE M12) (n=145,26)
    0
    9.7
        2=Much improved (OLE M12) (n=145,26)
    53.8
    39.3
        3=Minimally improved (OLE M12) (n=145,26)
    23.1
    26.2
        4=No Change (OLE M12) (n=145,26)
    19.2
    18.6
        5=Minimally worse (OLE M12) (n=145,26)
    3.8
    3.4
        6=Much worse (OLE M12) (n=145,26)
    0
    2.8
        7=Very much worse (OLE M12) (n=145,26)
    0
    0
        1=Very much improved (Last Assessment) (n=)
    6.3
    7.6
        2=Much improved (Last Assessment) (n=237,32)
    25.0
    27.4
        3=Minimally improved (Last Assessment) (n=237,32)
    25.0
    21.9
        4=No Change (Last Assessment) (n=237,32)
    40.6
    28.3
        5=Minimally worse (Last Assessment) (n=237,32)
    3.1
    7.2
        6=Much worse (Last Assessment) (n=237,32)
    0
    7.6
        7=Very much worse (Last Assessment) (n=237,32)
    0
    0
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in number of seizure-free days per 28 Days (ESC Confirmed) in OLE Period

    Close Top of page
    End point title
    Part 2: Change from Baseline in number of seizure-free days per 28 Days (ESC Confirmed) in OLE Period
    End point description
    A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE.
    End point type
    Secondary
    End point timeframe
    From Part 2 Baseline until end of OLE Period (up to 72 months)
    End point values
    Part 2: Cohort B- Overall Part 2: Cohort A- Overall
    Number of subjects analysed
    32
    241
    Units: seizure free days per 28 days
        median (full range (min-max))
    4.24 (-3.6 to 24.5)
    2.16 (-23.0 to 27.8)
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in duration of Longest interval between seizures that result in drops (ESC Confirmed) in OLE Period

    Close Top of page
    End point title
    Part 2: Change from Baseline in duration of Longest interval between seizures that result in drops (ESC Confirmed) in OLE Period
    End point description
    The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. Here, number of participants analyzed included those participants who were evaluable for the assessment.
    End point type
    Secondary
    End point timeframe
    From Part 2 Baseline until end of the OLE Period (up to 72 months)
    End point values
    Part 2: Cohort A- Overall Part 2: Cohort B- Overall
    Number of subjects analysed
    241
    27
    Units: days
        median (full range (min-max))
    4.0 (-10 to 360)
    6.0 (0 to 200)
    No statistical analyses for this end point

    Secondary: Part 2: Clinical Global Impression – Improvement as assessed by the Parent/Caregiver

    Close Top of page
    End point title
    Part 2: Clinical Global Impression – Improvement as assessed by the Parent/Caregiver
    End point description
    CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. Here, number of participants analyzed included those participants who were evaluable for the assessment. 'n' included those participants who were evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
    End point values
    Part 2: Cohort A- Overall Part 2: Cohort B- Overall
    Number of subjects analysed
    237
    32
    Units: percentage of participants
    number (not applicable)
        1=Very much improved (OLE D1) (n=232,32)
    6.9
    9.4
        2=Much improved (OLE D1) (n=232,32)
    16.8
    12.5
        3=Minimally improved (OLE D1) (n=232,32)
    24.6
    28.1
        4=No Change (OLE D1) (n=232,32)
    40.1
    43.8
        5=Minimally worse (OLE D1) (n=232,32)
    6.9
    3.1
        6=Much worse (OLE D1) (n=232,32)
    3.9
    3.1
        7=Very much worse (OLE D1) (n=232,32)
    0.9
    0
        1=Very much improved (OLE M1) (n=224,32)
    7.1
    12.5
        2=Much improved (OLE M1) (n=224,32)
    21.4
    15.6
        3=Minimally improved (OLE M1) (n=224,32)
    32.1
    31.3
        4=No Change (OLE M1) (n=224,32)
    29.5
    40.6
        5=Minimally worse (OLE M1) (n=224,32)
    5.8
    0
        6=Much worse (OLE M1) (n=224,32)
    4.0
    0
        7=Very much worse (OLE M1) (n=224,32)
    0
    0
        1=Very much improved (OLE M2) (n=219,31)
    7.3
    12.9
        2=Much improved (OLE M2) (n=219,31)
    25.6
    16.1
        3=Minimally improved (OLE M2) (n=219,31)
    32.0
    41.9
        4=No Change (OLE M2) (n=219,31)
    25.6
    22.6
        5=Minimally worse (OLE M2) (n=219,31)
    6.4
    6.5
        6=Much worse (OLE M2) (n=219,31)
    2.3
    0
        7=Very much worse (OLE M2) (n=219,31)
    0.9
    0
        1=Very much improved (OLE M3) (n=207,29)
    9.7
    13.8
        2=Much improved (OLE M3) (n=207,29)
    30.0
    10.3
        3=Minimally improved (OLE M3) (n=207,29)
    29.5
    37.9
        4=No Change (OLE M3) (n=207,29)
    19.3
    37.9
        5=Minimally worse (OLE M3) (n=207,29)
    9.7
    0
        6=Much worse (OLE M3) (n=207,29)
    0.5
    0
        7=Very much worse (OLE M3) (n=207,29)
    1.4
    0
        1=Very much improved (OLE M6) (n=186,29)
    13.4
    10.3
        2=Much improved (OLE M6) (n=186,29)
    30.1
    31.0
        3=Minimally improved (OLE M6) (n=186,29)
    27.4
    34.5
        4=No Change (OLE M6) (n=186,29)
    23.1
    20.7
        5=Minimally worse (OLE M6) (n=186,29)
    3.2
    0
        6=Much worse (OLE M6) (n=186,29)
    2.2
    3.4
        7=Very much worse (OLE M6) (n=186,29)
    0.5
    0
        1=Very much improved (OLE M9) (n=134,28)
    13.4
    14.3
        2=Much improved (OLE M9) (n=134,28)
    37.3
    25.0
        3=Minimally improved (OLE M9) (n=134,28)
    26.1
    21.4
        4=No Change (OLE M9) (n=134,28)
    14.2
    32.1
        5=Minimally worse (OLE M9) (n=134,28)
    8.2
    3.6
        6=Much worse (OLE M9) (n=134,28)
    0.7
    3.6
        7=Very much worse (OLE M9) (n=134,28)
    0
    0
        1=Very much improved (OLE M12) (n=149,26)
    16.8
    19.2
        2=Much improved (OLE M12) (n=149,26)
    34.2
    26.9
        3=Minimally improved (OLE M12) (n=149,26)
    26.8
    46.2
        4=No Change (OLE M12) (n=149,26)
    14.8
    3.8
        5=Minimally worse (OLE M12) (n=149,26)
    4.7
    3.8
        6=Much worse (OLE M12) (n=149,26)
    2.0
    0
        7=Very much worse (OLE M12) (n=149,26)
    0.7
    0
        1=Very much improved (Last Assessment) (n=237,32)
    11.4
    12.5
        2=Much improved (Last Assessment) (n=237,32)
    24.1
    28.1
        3=Minimally improved (Last Assessment) (n=237,32)
    24.5
    18.8
        4=No Change (Last Assessment) (n=237,32)
    25.3
    28.1
        5=Minimally worse (Last Assessment) (n=237,32)
    9.3
    9.4
        6=Much worse (Last Assessment) (n=237,32)
    3.4
    3.1
        7=Very much worse (Last Assessment) (n=237,32)
    2.1
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 up to 72 months
    Adverse event reporting additional description
    AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Part 1:Cohort A- Placebo
    Reporting group description
    Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Reporting group title
    Part 1: Cohort A- ZX008 0.8 mg/kg/day
    Reporting group description
    Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Reporting group title
    Part 1: Cohort A- ZX008 0.2 mg/kg/day
    Reporting group description
    Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Reporting group title
    Part 2: Cohort A- Overall
    Reporting group description
    All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.

    Reporting group title
    Part 1: Cohort B- ZX008 0.8 mg/kg/day
    Reporting group description
    Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Reporting group title
    Part 1: Cohort B- ZX008 0.2 mg/kg/day
    Reporting group description
    Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Reporting group title
    Part 2: Cohort B- Overall
    Reporting group description
    All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for subjects taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.

    Reporting group title
    Part 1: Cohort B- Placebo
    Reporting group description
    Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.

    Serious adverse events
    Part 1:Cohort A- Placebo Part 1: Cohort A- ZX008 0.8 mg/kg/day Part 1: Cohort A- ZX008 0.2 mg/kg/day Part 2: Cohort A- Overall Part 1: Cohort B- ZX008 0.8 mg/kg/day Part 1: Cohort B- ZX008 0.2 mg/kg/day Part 2: Cohort B- Overall Part 1: Cohort B- Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 87 (4.60%)
    10 / 87 (11.49%)
    4 / 89 (4.49%)
    41 / 247 (16.60%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    6 / 32 (18.75%)
    1 / 11 (9.09%)
         number of deaths (all causes)
    0
    1
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Distributive shock
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden unexplained death in epilepsy
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication of device insertion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Lung disorder
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    1 / 89 (1.12%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stereotypy
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood prolactin increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body in respiratory tract
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body in gastrointestinal tract
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    2 / 3
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Change in seizure presentation
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    2 / 89 (2.25%)
    10 / 247 (4.05%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 4
    3 / 12
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 87 (3.45%)
    0 / 89 (0.00%)
    8 / 247 (3.24%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    2 / 25
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure cluster
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemolytic uraemic syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eye movement disorder
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratoconus
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    1 / 89 (1.12%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    1 / 89 (1.12%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth loss
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infection
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 87 (2.30%)
    1 / 89 (1.12%)
    5 / 247 (2.02%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 6
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Part 1:Cohort A- Placebo Part 1: Cohort A- ZX008 0.8 mg/kg/day Part 1: Cohort A- ZX008 0.2 mg/kg/day Part 2: Cohort A- Overall Part 1: Cohort B- ZX008 0.8 mg/kg/day Part 1: Cohort B- ZX008 0.2 mg/kg/day Part 2: Cohort B- Overall Part 1: Cohort B- Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    60 / 87 (68.97%)
    68 / 87 (78.16%)
    64 / 89 (71.91%)
    166 / 247 (67.21%)
    7 / 11 (63.64%)
    10 / 11 (90.91%)
    30 / 32 (93.75%)
    8 / 11 (72.73%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    11 / 87 (12.64%)
    9 / 87 (10.34%)
    11 / 89 (12.36%)
    25 / 247 (10.12%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    7 / 32 (21.88%)
    1 / 11 (9.09%)
         occurrences all number
    13
    10
    12
    33
    0
    0
    12
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Fatigue
         subjects affected / exposed
    11 / 87 (12.64%)
    16 / 87 (18.39%)
    8 / 89 (8.99%)
    33 / 247 (13.36%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    11
    18
    10
    35
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    3 / 87 (3.45%)
    5 / 87 (5.75%)
    4 / 89 (4.49%)
    7 / 247 (2.83%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    5
    5
    4
    8
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    Cough
         subjects affected / exposed
    3 / 87 (3.45%)
    4 / 87 (4.60%)
    2 / 89 (2.25%)
    10 / 247 (4.05%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    3
    4
    3
    11
    0
    0
    2
    0
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    1 / 89 (1.12%)
    5 / 247 (2.02%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    5
    1
    0
    1
    0
    Irritability
         subjects affected / exposed
    5 / 87 (5.75%)
    4 / 87 (4.60%)
    9 / 89 (10.11%)
    6 / 247 (2.43%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
         occurrences all number
    5
    4
    9
    6
    0
    0
    3
    0
    Insomnia
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 87 (2.30%)
    0 / 89 (0.00%)
    11 / 247 (4.45%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    3
    2
    0
    11
    0
    0
    4
    0
    Affective disorder
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    0
    Agitation
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 87 (1.15%)
    1 / 89 (1.12%)
    4 / 247 (1.62%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    3
    1
    2
    4
    0
    0
    3
    0
    Investigations
    Echocardiogram abnormal
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 87 (2.30%)
    2 / 89 (2.25%)
    6 / 247 (2.43%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    6
    2
    2
    7
    0
    0
    2
    0
    Weight decreased
         subjects affected / exposed
    2 / 87 (2.30%)
    7 / 87 (8.05%)
    3 / 89 (3.37%)
    12 / 247 (4.86%)
    4 / 11 (36.36%)
    2 / 11 (18.18%)
    4 / 32 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    2
    7
    3
    12
    4
    2
    4
    1
    Blood prolactin increased
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 87 (3.45%)
    0 / 89 (0.00%)
    9 / 247 (3.64%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    8 / 32 (25.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    4
    0
    10
    0
    1
    14
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 87 (1.15%)
    5 / 87 (5.75%)
    2 / 89 (2.25%)
    7 / 247 (2.83%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    1 / 11 (9.09%)
         occurrences all number
    1
    5
    3
    10
    0
    0
    5
    1
    Face injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    0
    1
    Laceration
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 87 (3.45%)
    2 / 89 (2.25%)
    13 / 247 (5.26%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    1
    3
    2
    13
    0
    0
    2
    0
    Hand fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    1 / 89 (1.12%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 87 (1.15%)
    1 / 89 (1.12%)
    4 / 247 (1.62%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    1
    4
    0
    0
    0
    1
    Lip injury
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    6 / 247 (2.43%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    7
    0
    0
    3
    0
    Wound
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 87 (1.15%)
    1 / 89 (1.12%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    4 / 32 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    2
    1
    1
    2
    0
    0
    4
    0
    Cardiac disorders
    Mitral valve incompetence
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Nervous system disorders
    Lethargy
         subjects affected / exposed
    3 / 87 (3.45%)
    5 / 87 (5.75%)
    4 / 89 (4.49%)
    13 / 247 (5.26%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    3
    5
    4
    13
    0
    0
    0
    0
    Change in seizure presentation
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    17 / 247 (6.88%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    0
    19
    0
    0
    0
    0
    Seizure cluster
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    1 / 11 (9.09%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    5
    2
    Seizure
         subjects affected / exposed
    4 / 87 (4.60%)
    5 / 87 (5.75%)
    11 / 89 (12.36%)
    24 / 247 (9.72%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    4
    6
    13
    28
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    10 / 87 (11.49%)
    15 / 87 (17.24%)
    10 / 89 (11.24%)
    24 / 247 (9.72%)
    3 / 11 (27.27%)
    4 / 11 (36.36%)
    11 / 32 (34.38%)
    1 / 11 (9.09%)
         occurrences all number
    10
    16
    11
    26
    3
    5
    16
    1
    Tremor
         subjects affected / exposed
    1 / 87 (1.15%)
    2 / 87 (2.30%)
    2 / 89 (2.25%)
    7 / 247 (2.83%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    2
    2
    7
    1
    0
    0
    0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 87 (4.60%)
    10 / 87 (11.49%)
    10 / 89 (11.24%)
    13 / 247 (5.26%)
    2 / 11 (18.18%)
    3 / 11 (27.27%)
    5 / 32 (15.63%)
    0 / 11 (0.00%)
         occurrences all number
    4
    11
    10
    15
    2
    3
    5
    0
    Breath odour
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    5 / 87 (5.75%)
    8 / 87 (9.20%)
    5 / 89 (5.62%)
    18 / 247 (7.29%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    5 / 32 (15.63%)
    0 / 11 (0.00%)
         occurrences all number
    5
    10
    5
    22
    0
    0
    7
    0
    Dental caries
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    2 / 89 (2.25%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    1
    1
    0
    Vomiting
         subjects affected / exposed
    5 / 87 (5.75%)
    9 / 87 (10.34%)
    11 / 89 (12.36%)
    13 / 247 (5.26%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    5
    44
    16
    17
    0
    0
    0
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    3
    0
    Skin and subcutaneous tissue disorders
    Alopecia areata
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    Acne
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    1
    1
    0
    Eczema
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    2 / 89 (2.25%)
    2 / 247 (0.81%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    5 / 32 (15.63%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    2
    2
    1
    0
    7
    0
    Dermatitis diaper
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    Miliaria
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 87 (3.45%)
    0 / 89 (0.00%)
    3 / 247 (1.21%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    3
    0
    4
    1
    0
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 87 (2.30%)
    2 / 89 (2.25%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
         occurrences all number
    0
    2
    2
    2
    0
    0
    3
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 87 (2.30%)
    1 / 89 (1.12%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    2
    0
    Corona virus infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    12 / 32 (37.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    14
    0
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    2 / 247 (0.81%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    3
    0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 87 (4.60%)
    6 / 87 (6.90%)
    7 / 89 (7.87%)
    16 / 247 (6.48%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
         occurrences all number
    4
    7
    10
    20
    1
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    1 / 89 (1.12%)
    5 / 247 (2.02%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    1
    5
    0
    0
    2
    0
    Rhinitis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    1 / 89 (1.12%)
    5 / 247 (2.02%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    2
    5
    0
    0
    2
    0
    Oral herpes
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 87 (1.15%)
    0 / 89 (0.00%)
    0 / 247 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    8 / 87 (9.20%)
    7 / 87 (8.05%)
    4 / 89 (4.49%)
    31 / 247 (12.55%)
    0 / 11 (0.00%)
    2 / 11 (18.18%)
    9 / 32 (28.13%)
    2 / 11 (18.18%)
         occurrences all number
    10
    8
    5
    43
    0
    2
    18
    2
    Influenza
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 87 (1.15%)
    4 / 89 (4.49%)
    3 / 247 (1.21%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 32 (9.38%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    4
    3
    0
    0
    3
    1
    Herpes zoster
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 87 (0.00%)
    0 / 89 (0.00%)
    1 / 247 (0.40%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    13 / 87 (14.94%)
    32 / 87 (36.78%)
    18 / 89 (20.22%)
    39 / 247 (15.79%)
    3 / 11 (27.27%)
    3 / 11 (27.27%)
    4 / 32 (12.50%)
    2 / 11 (18.18%)
         occurrences all number
    15
    35
    18
    42
    3
    4
    4
    2

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jan 2018
    Amendment 1.0 provided updates and clarifications on the cardiac follow-up windows, added MS that result in a drop to the types of seizures assessed in the secondary endpoints, clarified inclusion and exclusion criteria, and clarified information to be recorded for adverse event reporting.
    29 Jul 2019
    Amendment 2.1 combined details from all country-specific protocols into 1 global document, incorporated corrections of the maximum daily dose for subjects taking concomitant STP, updated background information about completed and ongoing clinical trials, and provided updated information about the following: ECHO alert levels for trace regurgitation, endpoints and objectives, statistical analyses, increases in enrollment numbers, visit window allowances during the transition between Part 1 and Part 2, options for continuation of treatment after the end of the trial, prohibited medications, acceptable collection methods for urinalysis samples, phone visit options for Visit 13 and 23, and parameters regarding repeat laboratory sample collection during Baseline. It also included corrections to blood collection volumes and edits for consistency throughout.
    02 Jul 2020
    Amendment 3.1 provided study conduct information for the COVID-19 pandemic. This amendment also removed the Vineland Adaptive Behavior Scale (VABS) from the study assessments, included updated study drug storage excursions to align with updates to the Pharmacy Manual, and provided updated background information related to existing treatments for Lennox-Gastaut syndrome (LGS) and additional clinical and nonclinical study data.

    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-Thu May 01 13:14:05 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA