A Multicenter, Open-label, Pilot Study of Soticlestat (TAK-935/OV935) in Participants With 15Q Duplication Syndrome (Dup 15q) or Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder (ARCADE STUDY)

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03694275
Collaborator
Ovid Therapeutics Inc. (Industry)
20
Enrollment
8
Locations
2
Arms
22.7
Actual Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of soticlestat on the frequency of motor seizures for participants with Dup15q or CDD during the Maintenance Period.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

The drug being tested in this study is called soticlestat. Soticlestat is being tested to treat people with Dup 15q or CDD. This study will assess the effects of TAK-935 on seizure frequency, safety.

The study will enroll approximately 30 participants. Participants will be enrolled into 2 groups based on their diagnosis as: Dup 15q or CDD.

All participants will be asked to take soticlestat tablets twice daily with or without food.

The study comprises of 2 periods: Screening/Baseline Period and Treatment Period (Dose Optimization and Maintenance). The overall time to participate in this study is approximately 30 weeks, including 4 to 6 weeks Screening/Baseline Period, 20 weeks Treatment Period, 2 weeks Taper, and 2 weeks safety follow up period. Participants completing this study will have an option to enroll in the open-label extension (OLE) study, under a separate protocol.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-label, Pilot Study of TAK-935 (OV935) in Patients With 15Q Duplication Syndrome or CDKL5 Deficiency Disorder (ARCADE Study)
Actual Study Start Date :
Sep 10, 2018
Actual Primary Completion Date :
Jul 13, 2020
Actual Study Completion Date :
Jul 31, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Soticlestat Dup 15q

Soticlestat tablets twice daily (BID) orally or via gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, BID. Participants with Dup 15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.

Drug: Soticlestat
TAK-935 tablets
Other Names:
  • TAK-935
  • Experimental: Soticlestat CDD

    Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.

    Drug: Soticlestat
    TAK-935 tablets
    Other Names:
  • TAK-935
  • Outcome Measures

    Primary Outcome Measures

    1. Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period [Maintenance Period: Weeks 9 to 20]

      Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.

    Secondary Outcome Measures

    1. Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period [Treatment Period: Weeks 0 to 20]

      Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during the treatment period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.

    2. Percentage of Participants Considered as Treatment Responders During the Maintenance Period [Maintenance Period: Weeks 9 to 20]

      Responders are defined as having over 50% motor seizure reduction compared to Baseline. Percent reduction from Baseline (%) is defined as [(Maintenance Period motor Seizure Frequency - Baseline Period motor Seizure Frequency) divided by Baseline motor Seizure Frequency] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in motor seizures from Baseline.

    3. Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD [Treatment Period: Weeks 0 to 20]

      Seizure frequency is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period. Percent Change from Baseline is defined as (frequency of seizures during Treatment period - frequency of seizures at Baseline) divided by frequency of seizures at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. The data is reported only for CDD participants.

    4. Proportion of Motor Seizure-free Days in Participants During the Maintenance Period [Maintenance Period: Weeks 9 to 20]

      Seizure-free days is defined as number of days with zero motor seizure during the period the Maintenance Period divided by number of days participant was in the Maintenance Period.

    5. Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator [Baseline to Week 20]

      The CGI-S focuses on clinician's observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses where, 1= normal, not at all ill, 2= borderline mentally ill, 3= mildly ill, 4= moderately ill, 5= markedly ill, 6= severely ill and 7=amongst the most extremely ill participants. Negative change from Baseline indicates improvement.

    6. Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression [Week 20]

      CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 5-point scale, where, 0 = marked improvement and no side-effects, 1 = marked improvement and minimal side-effects, 2 = no change, 3 = minimal improvement and marked side-effects and 4 = unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement.

    7. Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family [Week 20]

      CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale where, 1 = very much improved, 2 = much improved, 3 = slightly improved, 4= no change, 5= slightly worse, 6= much worse and 7= very much worse and marked side-effects. Lower scores indicated improvement.

    8. Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels [Baseline to Week 20]

    9. Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy [Baseline to Week 20]

      Seizure Frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure during the period seizures were assessed multiplied by 28. Positive change from Baseline indicates seizure increase and negative change from Baseline indicates seizure decrease.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Clinical diagnosis of Dup 15q or CDKL5 deficiency disorder.

    2. Currently taking 1 to 6 antiepileptic drugs (AEDs) at a stable dose.

    Exclusion Criteria:
    1. Two or more episodes of convulsive status epilepticus per 3 months requiring hospitalization and intubation.

    2. Currently receiving a study drug or participated in a clinical study involving another investigational product in the previous month.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1UCLALos AngelesCaliforniaUnited States90095
    2Research Institute Children's Hospital ColoradoAuroraColoradoUnited States80045
    3Center for Rare Neurological DiseasesNorcrossGeorgiaUnited States30093
    4Center for Rare Neurological Diseases (CRND)--Massachusetts General HospitalBostonMassachusettsUnited States02114
    5Boston Children's Hospital Translational Neuroscience CenterBostonMassachusettsUnited States02115
    6Minnesota Epilepsy Group, P.A.Saint PaulMinnesotaUnited States55102
    7New York University (NYU)New YorkNew YorkUnited States10017
    8Columbia University Medical CenterNew YorkNew YorkUnited States10032

    Sponsors and Collaborators

    • Takeda
    • Ovid Therapeutics Inc.

    Investigators

    • Study Director: Medical Director Clinical Science, Takeda

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03694275
    Other Study ID Numbers:
    • TAK-935-18-002 (OV935)
    • U1111-1219-5787
    First Posted:
    Oct 3, 2018
    Last Update Posted:
    Apr 20, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takeda
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants took part in the study at 8 investigative sites in the United States from 10 September 2018 to 31 July 2020.
    Pre-assignment DetailParticipants with a diagnosis of 15q duplication syndrome (Dup15q) or CDKL5 deficiency disorder (CDD) were enrolled in 2 cohorts to receive treatment with TAK-935 for up to 20 weeks Treatment Period (8-week Dose Optimization Period and 12-week Maintenance Period).
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets twice daily (BID) orally or via gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Period Title: Overall Study
    STARTED812
    COMPLETED810
    NOT COMPLETED02

    Baseline Characteristics

    Arm/Group TitleSoticlestat Dup15qSoticlestat CDDTotal
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Total of all reporting groups
    Overall Participants81220
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    15.4
    (6.00)
    7.6
    (5.30)
    10.7
    (6.70)
    Sex: Female, Male (Count of Participants)
    Female
    3
    37.5%
    9
    75%
    12
    60%
    Male
    5
    62.5%
    3
    25%
    8
    40%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    8
    100%
    12
    100%
    20
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    8
    100%
    11
    91.7%
    19
    95%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    8.3%
    1
    5%
    Region of Enrollment (Count of Participants)
    United States
    8
    100%
    12
    100%
    20
    100%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    148.54
    (14.965)
    124.59
    (26.882)
    134.17
    (25.412)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    43.40
    (13.678)
    26.28
    (12.511)
    33.13
    (15.283)
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    19.21
    (4.149)
    16.00
    (1.874)
    17.28
    (3.314)

    Outcome Measures

    1. Primary Outcome
    TitlePercent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period
    DescriptionSeizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.
    Time FrameMaintenance Period: Weeks 9 to 20

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat (mITT) Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed are the number of participants with data available for analyses.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants811
    Median (Full Range) [percent change]
    11.7
    -23.6
    2. Secondary Outcome
    TitlePercent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period
    DescriptionSeizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during the treatment period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.
    Time FrameTreatment Period: Weeks 0 to 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants812
    Median (Full Range) [percent change]
    13.4
    -13.6
    3. Secondary Outcome
    TitlePercentage of Participants Considered as Treatment Responders During the Maintenance Period
    DescriptionResponders are defined as having over 50% motor seizure reduction compared to Baseline. Percent reduction from Baseline (%) is defined as [(Maintenance Period motor Seizure Frequency - Baseline Period motor Seizure Frequency) divided by Baseline motor Seizure Frequency] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in motor seizures from Baseline.
    Time FrameMaintenance Period: Weeks 9 to 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants811
    <=0% Reduction
    62.5
    781.3%
    27.3
    227.5%
    >0% to <25% Reduction
    12.5
    156.3%
    27.3
    227.5%
    >=25% to <50% Reduction
    12.5
    156.3%
    18.2
    151.7%
    >=50% to <75% Reduction
    0
    0%
    18.2
    151.7%
    >=75% to 100% Reduction
    12.5
    156.3%
    9.1
    75.8%
    4. Secondary Outcome
    TitlePercent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD
    DescriptionSeizure frequency is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period. Percent Change from Baseline is defined as (frequency of seizures during Treatment period - frequency of seizures at Baseline) divided by frequency of seizures at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. The data is reported only for CDD participants.
    Time FrameTreatment Period: Weeks 0 to 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed are all participants whose analyses were conducted using observed values and no imputation was done for missing data.
    Arm/Group TitleSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants6
    Median (Full Range) [percent change]
    -54.0
    5. Secondary Outcome
    TitleProportion of Motor Seizure-free Days in Participants During the Maintenance Period
    DescriptionSeizure-free days is defined as number of days with zero motor seizure during the period the Maintenance Period divided by number of days participant was in the Maintenance Period.
    Time FrameMaintenance Period: Weeks 9 to 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants811
    Median (Full Range) [days/28 days]
    0.1
    0.1
    6. Secondary Outcome
    TitleChange From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator
    DescriptionThe CGI-S focuses on clinician's observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses where, 1= normal, not at all ill, 2= borderline mentally ill, 3= mildly ill, 4= moderately ill, 5= markedly ill, 6= severely ill and 7=amongst the most extremely ill participants. Negative change from Baseline indicates improvement.
    Time FrameBaseline to Week 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Number analyzed is the number of participants with data available for analyses at the given timepoint.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants812
    Baseline
    5.0
    5.0
    Change From Baseline at Week 20
    0.0
    0.0
    7. Secondary Outcome
    TitlePercentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression
    DescriptionCGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 5-point scale, where, 0 = marked improvement and no side-effects, 1 = marked improvement and minimal side-effects, 2 = no change, 3 = minimal improvement and marked side-effects and 4 = unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement.
    Time FrameWeek 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses at given timepoint.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants612
    Week 20, Score 0
    33.3
    416.3%
    33.3
    277.5%
    Week 20, Score 1
    0
    0%
    33.3
    277.5%
    Week 20, Score 2
    50.0
    625%
    33.3
    277.5%
    Week 20, Score 3
    16.7
    208.8%
    0
    0%
    Week 20, Score 4
    0
    0%
    0
    0%
    8. Secondary Outcome
    TitlePercentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family
    DescriptionCGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale where, 1 = very much improved, 2 = much improved, 3 = slightly improved, 4= no change, 5= slightly worse, 6= much worse and 7= very much worse and marked side-effects. Lower scores indicated improvement.
    Time FrameWeek 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses at the given timepoint.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants612
    Week 20, Score 1
    0
    0%
    16.7
    139.2%
    Week 20, Score 2
    16.7
    208.8%
    25.0
    208.3%
    Week 20, Score 3
    33.3
    416.3%
    50.0
    416.7%
    Week 20, Score 4
    50.0
    625%
    0
    0%
    Week 20, Score 5
    0
    0%
    8.3
    69.2%
    Week 20, Score 6
    0
    0%
    0
    0%
    Week 20, Score 7
    0
    0%
    0
    0%
    9. Secondary Outcome
    TitleChange From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels
    Description
    Time FrameBaseline to Week 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the given timepoint.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants811
    Baseline
    57.08
    (24.195)
    115.29
    (73.587)
    Change from Baseline at Week 20
    -34.71
    (16.578)
    -75.64
    (29.284)
    10. Secondary Outcome
    TitleChange From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy
    DescriptionSeizure Frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure during the period seizures were assessed multiplied by 28. Positive change from Baseline indicates seizure increase and negative change from Baseline indicates seizure decrease.
    Time FrameBaseline to Week 20

    Outcome Measure Data

    Analysis Population Description
    mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    Measure Participants812
    Baseline
    128.4
    77.8
    Change From Baseline
    13.2
    -3.4

    Adverse Events

    Time FrameFrom the first dose to 30 days post-last dose of study treatment (Up to 24 weeks)
    Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Arm/Group TitleSoticlestat Dup15qSoticlestat CDD
    Arm/Group DescriptionSoticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
    All Cause Mortality
    Soticlestat Dup15qSoticlestat CDD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/8 (0%) 0/12 (0%)
    Serious Adverse Events
    Soticlestat Dup15qSoticlestat CDD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/8 (12.5%) 2/12 (16.7%)
    Immune system disorders
    Anaphylactic reaction1/8 (12.5%) 0/12 (0%)
    Infections and infestations
    Respiratory syncytial virus bronchiolitis0/8 (0%) 1/12 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure0/8 (0%) 1/12 (8.3%)
    Other (Not Including Serious) Adverse Events
    Soticlestat Dup15qSoticlestat CDD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/8 (87.5%) 12/12 (100%)
    Blood and lymphatic system disorders
    Eosinophilia1/8 (12.5%) 0/12 (0%)
    Gastrointestinal disorders
    Constipation0/8 (0%) 4/12 (33.3%)
    Diarrhoea1/8 (12.5%) 0/12 (0%)
    Frequent bowel movements0/8 (0%) 1/12 (8.3%)
    General disorders
    Fatigue2/8 (25%) 0/12 (0%)
    Asthenia0/8 (0%) 1/12 (8.3%)
    Peripheral swelling0/8 (0%) 1/12 (8.3%)
    Pain1/8 (12.5%) 0/12 (0%)
    Immune system disorders
    Seasonal allergy0/8 (0%) 1/12 (8.3%)
    Infections and infestations
    Ear infection0/8 (0%) 2/12 (16.7%)
    Nasopharyngitis1/8 (12.5%) 1/12 (8.3%)
    Respiratory tract infection0/8 (0%) 1/12 (8.3%)
    Sinusitis1/8 (12.5%) 0/12 (0%)
    Upper respiratory tract infection1/8 (12.5%) 0/12 (0%)
    Urinary tract infection0/8 (0%) 1/12 (8.3%)
    Injury, poisoning and procedural complications
    Face injury1/8 (12.5%) 0/12 (0%)
    Fall1/8 (12.5%) 0/12 (0%)
    Investigations
    Blood bicarbonate decreased0/8 (0%) 2/12 (16.7%)
    Activated partial thromboplastin time prolonged1/8 (12.5%) 0/12 (0%)
    Anticonvulsant drug level increased1/8 (12.5%) 0/12 (0%)
    Blood cholesterol increased0/8 (0%) 1/12 (8.3%)
    Blood creatine phosphokinase increased0/8 (0%) 1/12 (8.3%)
    Blood triglycerides increased0/8 (0%) 1/12 (8.3%)
    C-reactive protein increased0/8 (0%) 1/12 (8.3%)
    Electrocardiogram QT prolonged0/8 (0%) 1/12 (8.3%)
    Electrocardiogram ST-T change0/8 (0%) 1/12 (8.3%)
    Haematocrit increased0/8 (0%) 1/12 (8.3%)
    International normalised ratio increased1/8 (12.5%) 0/12 (0%)
    Low density lipoprotein increased0/8 (0%) 1/12 (8.3%)
    Neutrophil count decreased0/8 (0%) 1/12 (8.3%)
    Oxygen saturation decreased0/8 (0%) 1/12 (8.3%)
    Platelet count increased0/8 (0%) 1/12 (8.3%)
    White blood cell count increased0/8 (0%) 1/12 (8.3%)
    Nervous system disorders
    Seizure2/8 (25%) 1/12 (8.3%)
    Lethargy2/8 (25%) 0/12 (0%)
    Partial seizures0/8 (0%) 2/12 (16.7%)
    Tonic convulsion0/8 (0%) 2/12 (16.7%)
    Atonic seizures0/8 (0%) 1/12 (8.3%)
    Balance disorder1/8 (12.5%) 0/12 (0%)
    Drooling1/8 (12.5%) 0/12 (0%)
    Hypersomnia1/8 (12.5%) 0/12 (0%)
    Hypotonia1/8 (12.5%) 0/12 (0%)
    Somnolence0/8 (0%) 1/12 (8.3%)
    Tremor0/8 (0%) 1/12 (8.3%)
    Psychiatric disorders
    Agitation1/8 (12.5%) 1/12 (8.3%)
    Initial insomnia0/8 (0%) 1/12 (8.3%)
    Irritability0/8 (0%) 1/12 (8.3%)
    Sleep disorder0/8 (0%) 1/12 (8.3%)
    Renal and urinary disorders
    Neurogenic bladder0/8 (0%) 1/12 (8.3%)
    Urinary retentio0/8 (0%) 1/12 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Apnoea1/8 (12.5%) 0/12 (0%)
    Hyperventilation0/8 (0%) 1/12 (8.3%)
    Pneumonia aspiration0/8 (0%) 1/12 (8.3%)
    Skin and subcutaneous tissue disorders
    Rash1/8 (12.5%) 2/12 (16.7%)
    Pruritus1/8 (12.5%) 0/12 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.

    Results Point of Contact

    Name/TitleMedical Director
    OrganizationTakeda
    Phone+1-877-825-3327
    Emailtrialdisclosures@takeda.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03694275
    Other Study ID Numbers:
    • TAK-935-18-002 (OV935)
    • U1111-1219-5787
    First Posted:
    Oct 3, 2018
    Last Update Posted:
    Apr 20, 2021
    Last Verified:
    Mar 1, 2021