Dravet Syndrome (DS)
Conditions
Keywords
Drug Therapy
Brief summary
The main aim of the study is to learn if soticlestat, when given as an add-on therapy, reduces the number of convulsive seizures in children and young adults with DS. Participants will receive their standard antiseizure therapy, plus either a tablet of soticlestat or placebo for 16 weeks. A placebo looks just like soticlestat but will not have any medicine in it. Participants may continue treatment in an extension study, based on the extension study's entry criteria. Those that want to stop treatment will have a gradual dose reduction during 1 week and then be followed up for 2 weeks.
Detailed description
The drug being tested in this study is called soticlestat (TAK-935). Soticlestat as an adjunctive therapy will be assessed for efficacy, safety, and tolerability in pediatric and adult participants with DS. The study will enroll approximately 142 pediatric and young adult patients. Participants will be randomized at a 1:1 ratio to receive standard of care (SOC) plus one of the following adjunctive therapies: * Soticlestat or * Placebo The total daily dose of study drug will be calculated based on body weight in the 4 weeks Titration Period. Following the Titration Period, participants will continue to receive the same dose in the 12-weeks Maintenance Period. This multi-center trial will be conducted worldwide. The overall time to participate in the study will be from 22-25 weeks. At the end of the Full Treatment Period, participants have the option to either complete the study and taper off the investigational product or to enter the OLE if they meet eligibility requirements. If participants discontinue, they will be followed-up on phone call approximately 14 days after the last dose of study drug for safety.
Interventions
DRUGSoticlestat
Soticlestat mini-tablets or tablets.
DRUGPlacebo
Soticlestat placebo-matching mini-tablets or tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Has documented clinical diagnosis of DS. 2. Had ≥12 convulsive seizures over 12 weeks before screening based on the historical information and has had ≥4 convulsive seizures per 28 days during the 4- to 6-week prospective baseline period. 3. Weighs ≥10 kg at the screening visit (Visit 1). 4. Failure to control seizures despite appropriate trials of at least 1 ASM based on historical information and is currently on an antiseizure therapy or other treatment options considered as SOC. 5. Artisanal cannabidiols are allowed at a stable dose for at least 4 weeks before the screening visit (Visit 1); the dosing regimen and manufacturer should remain constant throughout the study (Artisanal cannabidiols will not be counted as ASMs.). 6. Currently taking 0 to 4 ASMs at stable doses for at least 4 weeks before the screening visit (Visit 1); benzodiazepines used chronically (daily) to treat seizures are considered ASMs. Fenfluramine and cannabidiol (Epidiolex) are allowed where available and should be counted as an ASM. ASM dosing regimen must remain constant throughout the study.
Exclusion criteria
1\. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, endocrine disease, malignancy including progressive tumors, or other abnormality that may impact the ability to participate in the study or that may potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the medical monitor may be warranted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period | Baseline; Full Treatment Period: Weeks 1 to 16 | Convulsive seizure frequency per 28 days was defined as the total number of convulsive seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Full Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100. |
| Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Maintenance Period | Baseline; Maintenance Period: Weeks 5 to 16 | Convulsive seizure frequency per 28 days was defined as the total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during Maintenance Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | Full Treatment Period: Weeks 1 to 16 | Percent reduction from Baseline (%) was defined as \[(Full Treatment Period Convulsive Seizure Frequency - Baseline Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Data was reported as reduction of ≤0%, \>0% to ≤25%, \>25% to ≤50%, \>50% to ≤75%, \>75% to ≤100% or more in seizures from Baseline. Percentages were rounded off to the nearest single decimal place. |
| Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Week 16 | The Care GI-I is a 7-point Likert scale that the caregiver used to rate improvement in overall seizure control, behavior, safety and tolerability after the initiation of study drug relative to Baseline (before treatment with the study drug). The participant was rated 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 parent/caregiver completed the Care GI-I via interview. Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place. |
| Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Week 16 | The CGI-I (Clinician) is a 7-point Likert scale that the investigator used to rate a participant's change (improvement) in overall seizure control, behavior, safety and tolerability, after the initiation of study drug relative to Baseline (before treatment with the study drug). The participant was rated 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 investigator or designee completed the CGI-I. Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place. |
| Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Week 16 | The CGI-I non-seizure symptoms instrument is a series of single-item assessments that the investigator used to rate improvement in the symptoms and impacts in select non-seizure domains (alertness, communication, and disruptive behaviors) since initiating the study drug. The participant was rated by the investigator for each domain 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). Lower scores indicated improvement. Data for percentage of participants categorized based on the responses for each domain are presented. Percentages were rounded off to the nearest single decimal place. |
| Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16 | Baseline, Week 16 | The QI-Disability tool is a parent/caregiver-reported questionnaire that evaluated the quality of life in children with intellectual disabilities. It contains 32 items covering 6 domains of quality of life: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Each QI-Disability item is rated on a Likert scale of: Never, Rarely, Sometimes, Often, and Very Often. Items were linearly transformed to a scale of 0 to 100, with higher scores representing better quality of life. Domain scores are calculated by averaging item scores. The domain scores are summed and divided by 6 to yield a total score. The total score ranges from 0 to 100, with higher scores indicating a better quality of life. A negative change from Baseline implies deteriorating quality of life. Mixed-effects model for repeated measures (MMRM) was used for analysis. |
| Percentage of Responders During Maintenance Period | Maintenance Period: Weeks 5 to 16 | Responders were defined as those with ≥50% reduction from Baseline in convulsive seizures during the Maintenance Period. Percentages were rounded off to the nearest single decimal place. |
| Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period | Baseline; Maintenance Period: Weeks 5 to 16 | Seizure frequency per 28 days was defined as the total number of seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Maintenance Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100. |
| Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period | Baseline; Full Treatment Period: Weeks 1 to 16 | Seizure frequency per 28 days was defined as the total number of seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Full Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100. |
| Change From Baseline in Percentage of Convulsive Seizure-free Days During the Full Treatment Period | Baseline up to Week 16 | Convulsive seizure-free days was defined as number of days a participant remained convulsive seizure-free after initiation of the treatment. The change from baseline in percentage of convulsive seizure-free days, was defined as the percentage of seizure-free days during the Full Treatment Period minus the percentage of seizure-free days during the Baseline. A linear model with treatment group and age stratum as factors and baseline percentage as a covariate was used for analysis. |
| Longest Convulsive Seizure-free Interval During the Full Treatment Period | Full Treatment Period: Weeks 1 to 16 | Longest convulsive seizure-free interval was defined as the longest time period that the participant remained convulsive seizure free after initiation of the treatment. A linear model with treatment group and age stratum as factors was used for analysis. |
| Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period | Full Treatment Period: Weeks 1 to 16 | Use of rescue ASM was recorded in the case report form (CRF) along with start and end date of medication. Based on the start and end dates for all rescue ASMs taken by a participant, the number of days during the Full Treatment Period when rescue ASM was used was derived. |
| Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Week 16 | The CGI-I seizure intensity and duration instrument was used by the parent/caregiver to rate changes in intensity and/or duration of the most impactful seizures from the first assessment. The participant's symptoms were rated on 7-point scale 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). Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place. |
| Percentage of Responders During the Full Treatment Period | Full Treatment Period: Weeks 1 to 16 | Responders were defined as those with ≥50% reduction from Baseline in convulsive seizures during the Full Treatment Period. Percentages were rounded off to the nearest single decimal place. |
Countries
Australia, Brazil, Canada, China, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Netherlands, Poland, Russia, Serbia, Spain, Ukraine, United States
Participant flow
Recruitment details
A total of 144 participants participated in the study at multiple investigative sites globally from 28 October 2021 to 11 April 2024.
Pre-assignment details
A total of 144 participants with a diagnosis of Dravet Syndrome (DS) were randomized in a 1:1 ratio to receive either soticlestat or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Soticlestat placebo-matching mini-tablets or tablets, orally or via G-tube or MIC-KEY button or J-tube, BID, up to 4 weeks during titration. Participants continued to receive the soticlestat placebo-matching mini-tablets or tablets for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period). Soticlestat matching tapering was done to maintain the blind if participants decided to discontinue the treatment. | 71 |
| Soticlestat Participants weighing \<45 kg: Soticlestat, mini-tablets, at the dose of 40 mg to 200 mg, orally or via G-tube or MIC-KEY button or J-tube, BID based on the body weight up to 4 weeks during titration. Participants continued to receive the dose that they were on at the end of the titration, for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with dose tapered down if participants decided to discontinue the treatment.
Participants weighing ≥45 kg: Soticlestat mini-tablets or tablets with a starting dose of 100 mg BID followed by 200 mg BID and, then 300 mg BID, up to 4 weeks during titration. Participants continued to receive 300 mg BID for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with dose tapered down if participants decided to discontinue the treatment. | 73 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 11 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Reason Not Specified | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 1 | 2 |
Baseline characteristics
| Characteristic | Soticlestat | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 10.1 years STANDARD_DEVIATION 5.04 | 10.3 years STANDARD_DEVIATION 5.04 | 10.5 years STANDARD_DEVIATION 5.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 130 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 51 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 39 Participants | 82 Participants | 43 Participants |
| Sex: Female, Male Female | 37 Participants | 72 Participants | 35 Participants |
| Sex: Female, Male Male | 36 Participants | 72 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 1 / 73 |
| other Total, other adverse events | 37 / 71 | 40 / 73 |
| serious Total, serious adverse events | 10 / 71 | 7 / 73 |
Outcome results
Primary
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period
Convulsive seizure frequency per 28 days was defined as the total number of convulsive seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Full Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.
Time frame: Baseline; Full Treatment Period: Weeks 1 to 16
Population: Modified Intent-to-Treat (mITT) Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period | -8.64 percent change |
| Soticlestat | Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period | -22.16 percent change |
p-value: =0.06195% CI: [-31.3, 0.24]ANCOVA
Primary
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Maintenance Period
Convulsive seizure frequency per 28 days was defined as the total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during Maintenance Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.
Time frame: Baseline; Maintenance Period: Weeks 5 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Maintenance Period | -11.99 percent change |
| Soticlestat | Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Maintenance Period | -23.29 percent change |
p-value: =0.08995% CI: [-30.51, 1.53]ANCOVA
Secondary
Change From Baseline in Percentage of Convulsive Seizure-free Days During the Full Treatment Period
Convulsive seizure-free days was defined as number of days a participant remained convulsive seizure-free after initiation of the treatment. The change from baseline in percentage of convulsive seizure-free days, was defined as the percentage of seizure-free days during the Full Treatment Period minus the percentage of seizure-free days during the Baseline. A linear model with treatment group and age stratum as factors and baseline percentage as a covariate was used for analysis.
Time frame: Baseline up to Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percentage of Convulsive Seizure-free Days During the Full Treatment Period | 2.74 percentage of days | Standard Error 1.784 |
| Soticlestat | Change From Baseline in Percentage of Convulsive Seizure-free Days During the Full Treatment Period | 3.54 percentage of days | Standard Error 1.719 |
95% CI: [-3.81, 5.4]
Secondary
Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16
The QI-Disability tool is a parent/caregiver-reported questionnaire that evaluated the quality of life in children with intellectual disabilities. It contains 32 items covering 6 domains of quality of life: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Each QI-Disability item is rated on a Likert scale of: Never, Rarely, Sometimes, Often, and Very Often. Items were linearly transformed to a scale of 0 to 100, with higher scores representing better quality of life. Domain scores are calculated by averaging item scores. The domain scores are summed and divided by 6 to yield a total score. The total score ranges from 0 to 100, with higher scores indicating a better quality of life. A negative change from Baseline implies deteriorating quality of life. Mixed-effects model for repeated measures (MMRM) was used for analysis.
Time frame: Baseline, Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16 | 2.81 score on a scale | Standard Deviation 10.119 |
| Soticlestat | Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16 | -1.23 score on a scale | Standard Deviation 15.438 |
p-value: =0.18995% CI: [-7.59, 1.52]MMRM
Secondary
Longest Convulsive Seizure-free Interval During the Full Treatment Period
Longest convulsive seizure-free interval was defined as the longest time period that the participant remained convulsive seizure free after initiation of the treatment. A linear model with treatment group and age stratum as factors was used for analysis.
Time frame: Full Treatment Period: Weeks 1 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Longest Convulsive Seizure-free Interval During the Full Treatment Period | 16.7 days | Standard Error 2.15 |
| Soticlestat | Longest Convulsive Seizure-free Interval During the Full Treatment Period | 22.3 days | Standard Error 2.08 |
95% CI: [0.1, 11.2]
Secondary
Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period
Use of rescue ASM was recorded in the case report form (CRF) along with start and end date of medication. Based on the start and end dates for all rescue ASMs taken by a participant, the number of days during the Full Treatment Period when rescue ASM was used was derived.
Time frame: Full Treatment Period: Weeks 1 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period | 4.0 days | Standard Error 0.81 |
| Soticlestat | Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period | 2.9 days | Standard Error 0.78 |
95% CI: [-3.1, 1]
Secondary
Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period
Percent reduction from Baseline (%) was defined as \[(Full Treatment Period Convulsive Seizure Frequency - Baseline Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Data was reported as reduction of ≤0%, \>0% to ≤25%, \>25% to ≤50%, \>50% to ≤75%, \>75% to ≤100% or more in seizures from Baseline. Percentages were rounded off to the nearest single decimal place.
Time frame: Full Treatment Period: Weeks 1 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >0% to ≤25% Reduction | 32.4 percentage of participants |
| Placebo | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >50% to ≤75% Reduction | 8.5 percentage of participants |
| Placebo | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >25% to ≤50% Reduction | 18.3 percentage of participants |
| Placebo | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >75% to ≤100% Reduction | 1.4 percentage of participants |
| Placebo | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | ≤0% Reduction | 39.4 percentage of participants |
| Soticlestat | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >75% to ≤100% Reduction | 13.7 percentage of participants |
| Soticlestat | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | ≤0% Reduction | 31.5 percentage of participants |
| Soticlestat | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >0% to ≤25% Reduction | 20.5 percentage of participants |
| Soticlestat | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >25% to ≤50% Reduction | 20.5 percentage of participants |
| Soticlestat | Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period | >50% to ≤75% Reduction | 13.7 percentage of participants |
Secondary
Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16
The Care GI-I is a 7-point Likert scale that the caregiver used to rate improvement in overall seizure control, behavior, safety and tolerability after the initiation of study drug relative to Baseline (before treatment with the study drug). The participant was rated 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 parent/caregiver completed the Care GI-I via interview. Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place.
Time frame: Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 3: Minimally Improved | 22.1 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 7: Very Much Worse | 1.5 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 1: Very Much Improved | 1.5 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 2: Much Improved | 11.8 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 4: No Change | 47.1 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 5: Minimally Worse | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 6: Much Worse | 5.9 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 7: Very Much Worse | 1.5 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 4: No Change | 27.3 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 6: Much Worse | 3.0 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 1: Very Much Improved | 4.5 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 5: Minimally Worse | 7.6 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 2: Much Improved | 27.3 percentage of participants |
| Soticlestat | Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 3: Minimally Improved | 28.8 percentage of participants |
p-value: =0.00495% CI: [1.33, 4.72]Cumulative Logit Model
Secondary
Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16
The CGI-I non-seizure symptoms instrument is a series of single-item assessments that the investigator used to rate improvement in the symptoms and impacts in select non-seizure domains (alertness, communication, and disruptive behaviors) since initiating the study drug. The participant was rated by the investigator for each domain 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). Lower scores indicated improvement. Data for percentage of participants categorized based on the responses for each domain are presented. Percentages were rounded off to the nearest single decimal place.
Time frame: Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 6: Much Worse | 1.4 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 5: Minimally Worse | 5.6 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 1: Very Much Improved | 2.8 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 2: Much Improved | 8.5 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 3: Minimally Improved | 14.1 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 4: No Change | 67.6 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 7: Very Much Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 1: Very much Improved | 1.4 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 2: Much Improved | 11.3 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 3: Minimally Improved | 18.3 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 4: No Change | 62.0 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 5: Minimally Worse | 4.2 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 6: Much Worse | 2.8 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 7: Very Much Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 1: Very Much Improved | 1.4 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 2: Much Improved | 4.2 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 3: Minimally Improved | 14.1 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 4: No Change | 69.0 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 5: Minimally Worse | 11.3 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 6: Much Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 7: Very Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 4: No Change | 62.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 5: Minimally Worse | 8.5 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 5: Minimally Worse | 4.2 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 1: Very Much Improved | 7.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 3: Minimally Improved | 16.9 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 6: Much Worse | 1.4 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 3: Minimally Improved | 14.1 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 7: Very Much Worse | 1.4 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 4: No Change | 70.4 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 5: Minimally Worse | 4.2 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 2: Much Improved | 4.2 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 6: Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 7: Very Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Alertness: Score 7: Very Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 4: No Change | 64.8 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 1: Very much Improved | 4.2 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 1: Very Much Improved | 1.4 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 2: Much Improved | 5.6 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 6: Much Worse | 1.4 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Communication: Score 3: Minimally Improved | 22.5 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 | Disruptive Behaviors: Score 2: Much Improved | 5.6 percentage of participants |
Comparison: Alertnessp-value: =0.74195% CI: [0.56, 2.26]Cumulative Logit Model
Comparison: Communicationp-value: =0.90195% CI: [0.54, 2.02]Cumulative Logit Model
Comparison: Disruptive Behaviorsp-value: =0.69395% CI: [0.58, 2.28]Cumulative Logit Model
Secondary
Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16
The CGI-I seizure intensity and duration instrument was used by the parent/caregiver to rate changes in intensity and/or duration of the most impactful seizures from the first assessment. The participant's symptoms were rated on 7-point scale 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). Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place.
Time frame: Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 7: Very Much Worse | 1.4 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 6: Much Worse | 8.7 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 3: Minimally Improved | 15.9 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 2: Much Improved | 4.3 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 4: No Change | 59.4 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 1: Very Much Improved | 4.3 percentage of participants |
| Placebo | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 5: Minimally Worse | 5.8 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 1: Very Much Improved | 10.8 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 6: Much Worse | 6.2 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 7: Very Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 5: Minimally Worse | 1.5 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 2: Much Improved | 24.6 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 3: Minimally Improved | 23.1 percentage of participants |
| Soticlestat | Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 | Score 4: No Change | 33.8 percentage of participants |
p-value: <0.00195% CI: [1.87, 7.13]Cumulative Logit Model
Secondary
Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16
The CGI-I (Clinician) is a 7-point Likert scale that the investigator used to rate a participant's change (improvement) in overall seizure control, behavior, safety and tolerability, after the initiation of study drug relative to Baseline (before treatment with the study drug). The participant was rated 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 investigator or designee completed the CGI-I. Lower scores indicate improvement. Percentages were rounded off to the nearest single decimal place.
Time frame: Week 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 2: Much Improved | 8.5 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 4: No Change | 59.2 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 1: Very Much Improved | 2.8 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 3: Minimally Improved | 15.5 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 6: Much Worse | 8.5 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 7: Very Much Worse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 5: Minimally Worse | 5.6 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 7: Very Much Worse | 0.0 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 6: Much Worse | 1.4 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 1: Very Much Improved | 7.0 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 2: Much Improved | 25.4 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 3: Minimally Improved | 19.7 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 4: No Change | 38.0 percentage of participants |
| Soticlestat | Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 | Score 5: Minimally Worse | 8.5 percentage of participants |
p-value: =0.00395% CI: [1.37, 4.87]Cumulative Logit Model
Secondary
Percentage of Responders During Maintenance Period
Responders were defined as those with ≥50% reduction from Baseline in convulsive seizures during the Maintenance Period. Percentages were rounded off to the nearest single decimal place.
Time frame: Maintenance Period: Weeks 5 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders During Maintenance Period | 11.8 percentage of participants |
| Soticlestat | Percentage of Responders During Maintenance Period | 30.4 percentage of participants |
p-value: =0.0195% CI: [1.3, 7.96]Cochran-Mantel-Haenszel
Secondary
Percentage of Responders During the Full Treatment Period
Responders were defined as those with ≥50% reduction from Baseline in convulsive seizures during the Full Treatment Period. Percentages were rounded off to the nearest single decimal place.
Time frame: Full Treatment Period: Weeks 1 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders During the Full Treatment Period | 9.9 percentage of participants |
| Soticlestat | Percentage of Responders During the Full Treatment Period | 27.4 percentage of participants |
p-value: =0.00895% CI: [1.36, 9.49]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period
Seizure frequency per 28 days was defined as the total number of seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Full Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.
Time frame: Baseline; Full Treatment Period: Weeks 1 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period | -7.46 percent change |
| Soticlestat | Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period | -9.27 percent change |
p-value: =0.63794% CI: [-26.31, 10.13]ANCOVA
Secondary
Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period
Seizure frequency per 28 days was defined as the total number of seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Maintenance Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.
Time frame: Baseline; Maintenance Period: Weeks 5 to 16
Population: mITT Analysis Set included all randomized participants who had received at least one dose of study drug and had been assessed for seizures for at least one day in the Full Treatment Period. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period | -11.89 percent change |
| Soticlestat | Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period | -17.24 percent change |
p-value: =0.56595% CI: [-29.01, 7.87]ANCOVA