15q Duplication Syndrome, CDKL5 Deficiency Disease
Conditions
Keywords
Drug Therapy, 15q Duplication Syndrome (Dup15q), CDKL5 Deficiency Disorder (CDD), Brain Diseases, Epilepsy, Central Nervous System Diseases, Autism, Cholesterol 24S-hydroxylase inhibitor, Anti-epilepsy drug, Anticonvulsants
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.
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.
Interventions
DRUGSoticlestat
TAK-935 tablets
Sponsors
Healx AI
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels | Baseline to Week 20 | — |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 8 investigative sites in the United States from 10 September 2018 to 31 July 2020.
Pre-assignment details
Participants 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).
Participants by arm
| Arm | Count |
|---|---|
| Soticlestat Dup15q Soticlestat 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. | 8 |
| 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. | 12 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Reason not Specified | 0 | 1 |
Baseline characteristics
| Characteristic | Soticlestat Dup15q | Total | Soticlestat CDD |
|---|---|---|---|
| Age, Continuous | 15.4 years STANDARD_DEVIATION 6 | 10.7 years STANDARD_DEVIATION 6.7 | 7.6 years STANDARD_DEVIATION 5.3 |
| Body Mass Index (BMI) | 19.21 kg/m^2 STANDARD_DEVIATION 4.149 | 17.28 kg/m^2 STANDARD_DEVIATION 3.314 | 16.00 kg/m^2 STANDARD_DEVIATION 1.874 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 20 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 148.54 cm STANDARD_DEVIATION 14.965 | 134.17 cm STANDARD_DEVIATION 25.412 | 124.59 cm STANDARD_DEVIATION 26.882 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 19 Participants | 11 Participants |
| Region of Enrollment United States | 8 Participants | 20 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
| Weight | 43.40 kg STANDARD_DEVIATION 13.678 | 33.13 kg STANDARD_DEVIATION 15.283 | 26.28 kg STANDARD_DEVIATION 12.511 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 12 |
| other Total, other adverse events | 7 / 8 | 12 / 12 |
| serious Total, serious adverse events | 1 / 8 | 2 / 12 |
Outcome results
Primary
Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period
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.
Time frame: Maintenance Period: Weeks 9 to 20
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Soticlestat Dup15q | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period | 11.7 percent change |
| Soticlestat CDD | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period | -23.6 percent change |
Secondary
Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator
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.
Time frame: Baseline to Week 20
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Soticlestat Dup15q | Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator | Baseline | 5.0 score on scale |
| Soticlestat Dup15q | Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator | Change From Baseline at Week 20 | 0.0 score on scale |
| Soticlestat CDD | Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator | Baseline | 5.0 score on scale |
| Soticlestat CDD | Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator | Change From Baseline at Week 20 | 0.0 score on scale |
Secondary
Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy
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.
Time frame: Baseline to Week 20
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Soticlestat Dup15q | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 128.4 seizures per 28 days |
| Soticlestat Dup15q | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Change From Baseline | 13.2 seizures per 28 days |
| Soticlestat CDD | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 77.8 seizures per 28 days |
| Soticlestat CDD | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Change From Baseline | -3.4 seizures per 28 days |
Secondary
Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels
Time frame: Baseline to Week 20
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soticlestat Dup15q | Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels | Change from Baseline at Week 20 | -34.71 ng/mL | Standard Deviation 16.578 |
| Soticlestat Dup15q | Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels | Baseline | 57.08 ng/mL | Standard Deviation 24.195 |
| Soticlestat CDD | Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels | Baseline | 115.29 ng/mL | Standard Deviation 73.587 |
| Soticlestat CDD | Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels | Change from Baseline at Week 20 | -75.64 ng/mL | Standard Deviation 29.284 |
Secondary
Percentage of Participants Considered as Treatment Responders During the Maintenance Period
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.
Time frame: Maintenance Period: Weeks 9 to 20
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Soticlestat Dup15q | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >0% to <25% Reduction | 12.5 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=50% to <75% Reduction | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=25% to <50% Reduction | 12.5 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=75% to 100% Reduction | 12.5 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | <=0% Reduction | 62.5 percentage of participants |
| Soticlestat CDD | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=75% to 100% Reduction | 9.1 percentage of participants |
| Soticlestat CDD | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | <=0% Reduction | 27.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >0% to <25% Reduction | 27.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=25% to <50% Reduction | 18.2 percentage of participants |
| Soticlestat CDD | Percentage of Participants Considered as Treatment Responders During the Maintenance Period | >=50% to <75% Reduction | 18.2 percentage of participants |
Secondary
Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family
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.
Time frame: Week 20
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 3 | 33.3 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 5 | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 2 | 16.7 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 6 | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 4 | 50.0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 7 | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 1 | 0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 7 | 0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 1 | 16.7 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 2 | 25.0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 3 | 50.0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 4 | 0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 5 | 8.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | Week 20, Score 6 | 0 percentage of participants |
Secondary
Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression
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.
Time frame: Week 20
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Soticlestat Dup15q | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 1 | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 3 | 16.7 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 2 | 50.0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 4 | 0 percentage of participants |
| Soticlestat Dup15q | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 0 | 33.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 4 | 0 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 0 | 33.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 1 | 33.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 2 | 33.3 percentage of participants |
| Soticlestat CDD | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | Week 20, Score 3 | 0 percentage of participants |
Secondary
Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD
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.
Time frame: Treatment Period: Weeks 0 to 20
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Soticlestat Dup15q | Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD | -54.0 percent change |
Secondary
Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period
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.
Time frame: Treatment Period: Weeks 0 to 20
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Soticlestat Dup15q | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period | 13.4 percent change |
| Soticlestat CDD | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period | -13.6 percent change |
Secondary
Proportion of Motor Seizure-free Days in Participants During the Maintenance Period
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.
Time frame: Maintenance Period: Weeks 9 to 20
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Soticlestat Dup15q | Proportion of Motor Seizure-free Days in Participants During the Maintenance Period | 0.1 days/28 days |
| Soticlestat CDD | Proportion of Motor Seizure-free Days in Participants During the Maintenance Period | 0.1 days/28 days |