Dravet Syndrome, Epilepsy, Lennox-Gastaut Syndrome
Conditions
Keywords
Drug Therapy, Brain Diseases, Central Nervous System Diseases, Tuberous Sclerosis, CDKL5 deficiency disorder, Dup15Q syndrome, Anoxic brain injury, Infantile spams, West syndrome, Cortical dysplasia, SCN1A, OV-935, Cholesterol 24S-hydroxylase inhibitor, Seizure, Anti-epileptic drug, Anticonvulsants, Nervous System Diseases, Drop seizure, Atonic seizure
Brief summary
The purpose of this study is to investigate the effect on the frequency of all seizures (convulsive and drop) in participants treated with TAK-935 compared to placebo.
Detailed description
The drug being tested in this study is called TAK-935 (OV935). This randomized, double-blind study will assess the effects of TAK-935 (OV935), compared to placebo, on efficacy, safety, and tolerability in pediatric participants with Dravet syndrome (DS) or Lennox Gastaut syndrome (LGS). This multi-center trial will be conducted worldwide and will enroll approximately 126 participants. Participants will be randomized based on their diagnosis in 2 categories; DS or LGS. The study will consist of 2 periods: Screening Period and Treatment Period. The overall duration of Treatment Period is up to 20 weeks including 8-week Dose Optimization Period and 12-week Maintenance Period. The overall time to participants in this study is approximately 30 weeks. Participants completing this study will have an option to enroll in the open-label extension study, under a separate protocol.
Interventions
DRUGTAK-935
TAK-935 tablets or mini-tablets.
DRUGPlacebo
TAK-935 placebo-matching tablets or mini-tablets.
Sponsors
Takeda
Healx AI
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 17 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female participants aged greater than or equal to (\>=) 2 and less than or equal to (\<=) 17 years 2. Clinical diagnosis of DS or LGS 3. Weight of \>=10 kilogram (kg) at the Screening visit 4. Currently taking 1 to 4 anti-epileptic drugs (AEDs) at a stable dose 5. Failed to become and remain seizure free with trials of at least 2 AEDs
Exclusion criteria
1. Has been admitted to a medical facility and intubated for treatment of status epilepticus 2 or more times in the 3 months immediately prior to the screening visit 2. Non-epileptic events that cannot be reliably distinguished from epileptic seizures 3. Participation in a clinical study involving another study drug in the previous month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period | Baseline; Maintenance Period: Weeks 9 to 20 | Seizure frequency per 28 days is defined as total number of seizures (convulsive seizures for DS, drop seizures for LGS) reported during the period divided by number of days during the period seizures were assessed 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. Negative percent change from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period | Baseline; Treatment Period: Weeks 0 to 20 | Seizure Frequency per 28 days is defined as total number of Seizures reported (convulsive seizures for DS, drop seizures for LGS) during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during treatment period - frequency of seizures per 28 days at baseline) divided by frequency of seizures per 28 days at baseline multiplied by 100. Negative percent change from Baseline indicates improvement. |
| Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period | Baseline; Maintenance Period: Weeks 9 to 20 | Convulsive seizure frequency per 28 days is defined as 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 (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement. |
| Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period | Baseline; Maintenance Period: Weeks 9 to 20 | Drop seizure frequency per 28 days is defined as total number of drop seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement. |
| Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Maintenance Period: Weeks 9 to 20 | Responders are defined as having over 50% drop seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline. |
| Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Maintenance Period: Weeks 9 to 20 | Responders are defined as having over 50% convulsive seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline. |
| Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) Responses of Investigator Reported Impression of Efficacy and Tolerability of Study Drug | Baseline and Week 20 | The CGI-Severity (CGI-S) focuses on clinicians' 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 from 1 (normal) through to 7 (amongst the most severely ill participants). A negative change from Baseline indicates improvement. |
| Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | 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, 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. |
| Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20 | The Care GI-C is rated on a 7-point scale, with the severity of illness 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. Lower scores indicated improvement. |
| Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline and Week 24 | A negative change from Baseline indicates improvement. |
| Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline and Week 20 | Seizure frequency was based on convulsive seizures for the participants in the Dravet Syndrome Indication and Drop Seizures for the participants in the LGS Indication. Seizure frequency per 28 days = (total number of seizures reported during the period) / (number of days during the period seizures were assessed) \* 28. A negative change from Baseline indicates improvement. |
Countries
Australia, Canada, China, Israel, Poland, Portugal, Spain, United States
Contacts
STUDY_DIRECTORMedical Director Clinical Science
Takeda (Note: This product was divested to Mistrau Bio, Inc. in 2026)
Participant flow
Recruitment details
Participants took part in the study at 45 investigative sites globally from 8 August 2018 to 20 July 2020.
Pre-assignment details
Participants with a diagnosis of Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) were enrolled and randomized in a 1:1 ratio to double-blind treatment with TAK-935 or matching placebo for up to the 20-week Treatment Period (8-week Dose Optimization Period and 12-week Maintenance Period).
Participants by arm
| Arm | Count |
|---|---|
| Placebo TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20. | 70 |
| TAK-935 TAK-935 tablets orally or via G-tube/PEG tube, BID. Participants weighing \<60 kg 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. | 71 |
| Total | 141 |
Baseline characteristics
| Characteristic | Placebo | TAK-935 | Total |
|---|---|---|---|
| Age, Continuous | 9.5 years STANDARD_DEVIATION 3.93 | 9.6 years STANDARD_DEVIATION 4.14 | 9.5 years STANDARD_DEVIATION 4.02 |
| Body Mass Index (BMI) | 17.63 (kg/m^2) STANDARD_DEVIATION 4.378 | 17.43 (kg/m^2) STANDARD_DEVIATION 4.048 | 17.53 (kg/m^2) STANDARD_DEVIATION 4.198 |
| Clinical Global Impression of Severity (CGI-S) Responses of Investigator | 4.8 score on a scale | 4.5 score on a scale | 4.65 score on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 11 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 60 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 132.4 cm STANDARD_DEVIATION 20.34 | 134.7 cm STANDARD_DEVIATION 21.34 | 133.6 cm STANDARD_DEVIATION 20.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 22 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 49 Participants | 96 Participants |
| Region of Enrollment Australia | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Canada | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment China | 20 Participants | 21 Participants | 41 Participants |
| Region of Enrollment Israel | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Poland | 12 Participants | 17 Participants | 29 Participants |
| Region of Enrollment Portugal | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Spain | 11 Participants | 8 Participants | 19 Participants |
| Region of Enrollment United States | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Female | 28 Participants | 22 Participants | 50 Participants |
| Sex: Female, Male Male | 42 Participants | 49 Participants | 91 Participants |
| Weight | 32.8 kg STANDARD_DEVIATION 15.98 | 33.3 kg STANDARD_DEVIATION 15.11 | 33.0 kg STANDARD_DEVIATION 15.49 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 71 |
| other Total, other adverse events | 52 / 70 | 55 / 71 |
| serious Total, serious adverse events | 13 / 70 | 11 / 71 |
Outcome results
Primary
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period
Seizure frequency per 28 days is defined as total number of seizures (convulsive seizures for DS, drop seizures for LGS) reported during the period divided by number of days during the period seizures were assessed 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. Negative percent change from Baseline indicates improvement.
Time frame: Baseline; Maintenance Period: Weeks 9 to 20
Population: Efficacy Analysis Set included all Modified Intent-to-Treat (mITT) participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period | 3.11 percent change |
| TAK-935 | Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period | -27.76 percent change |
p-value: 0.000795% CI: [-46.99, -13.19]Ranked ANCOVA
Secondary
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) Responses of Investigator Reported Impression of Efficacy and Tolerability of Study Drug
The CGI-Severity (CGI-S) focuses on clinicians' 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 from 1 (normal) through to 7 (amongst the most severely ill participants). A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) Responses of Investigator Reported Impression of Efficacy and Tolerability of Study Drug | -0.3 score on scale | Standard Deviation 0.15 |
| TAK-935 | Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) Responses of Investigator Reported Impression of Efficacy and Tolerability of Study Drug | -0.2 score on scale | Standard Deviation 0.14 |
p-value: 0.682995% CI: [-0.32, 0.49]Mixed-Model Repeated Measure (MMRM)
Secondary
Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy
A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 24
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2, with available data. Number analyzed is the number of participants with Baseline and Week 24 data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 102.77 mg/dL | Standard Deviation 50.385 |
| TAK-935 | Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 102.20 mg/dL | Standard Deviation 62.332 |
| TAK-935 | Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy | Change from Baseline at Week 24 | -0.10 mg/dL | — |
Secondary
Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy
Seizure frequency was based on convulsive seizures for the participants in the Dravet Syndrome Indication and Drop Seizures for the participants in the LGS Indication. Seizure frequency per 28 days = (total number of seizures reported during the period) / (number of days during the period seizures were assessed) \* 28. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2, with available data. Number analyzed is the number of participants with Baseline and Week 24 data available for analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 31.00 seizures per 28 days |
| Placebo | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Change from Baseline at Week 20 | 0.30 seizures per 28 days |
| TAK-935 | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Baseline | 32.12 seizures per 28 days |
| TAK-935 | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Change from Baseline at Week 20 | -6.29 seizures per 28 days |
Secondary
Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935
The Care GI-C is rated on a 7-point scale, with the severity of illness 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. Lower scores indicated improvement.
Time frame: Week 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 3 | 18.4 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 5 | 8.2 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 2 | 12.2 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 6 | 4.1 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 4 | 55.1 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 7 | 0 percentage of participants |
| Placebo | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 1 | 2.0 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 7 | 0 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 1 | 13.8 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 2 | 10.3 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 3 | 32.8 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 4 | 37.9 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 5 | 3.4 percentage of participants |
| TAK-935 | Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 | Week 20, Score 6 | 1.7 percentage of participants |
Secondary
Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935
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, 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: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 1 | 2.0 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 3 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 2 | 85.7 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 4 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 0 | 12.2 percentage of participants |
| TAK-935 | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 4 | 1.7 percentage of participants |
| TAK-935 | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 0 | 17.2 percentage of participants |
| TAK-935 | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 1 | 15.5 percentage of participants |
| TAK-935 | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 2 | 65.5 percentage of participants |
| TAK-935 | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 | Week 20, Score 3 | 0 percentage of participants |
Secondary
Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period
Responders are defined as having over 50% convulsive seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline.
Time frame: Maintenance Period: Weeks 9 to 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Only participants with Dravet syndrome stratum indication were analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 25% or More in Convulsive Seizures from Baseline | 13.6 percentage of participants |
| Placebo | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 50% or More in Convulsive Seizures from Baseline | 0 percentage of participants |
| Placebo | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 75% or More in Convulsive Seizures from Baseline | 0 percentage of participants |
| Placebo | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 100% in Convulsive Seizures from Baseline | 0 percentage of participants |
| TAK-935 | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 100% in Convulsive Seizures from Baseline | 8.3 percentage of participants |
| TAK-935 | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 25% or More in Convulsive Seizures from Baseline | 66.7 percentage of participants |
| TAK-935 | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 75% or More in Convulsive Seizures from Baseline | 20.8 percentage of participants |
| TAK-935 | Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 50% or More in Convulsive Seizures from Baseline | 41.7 percentage of participants |
Secondary
Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period
Responders are defined as having over 50% drop seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline.
Time frame: Maintenance Period: Weeks 9 to 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Only participants with LGS stratum indication were analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 25% or More in Drop Seizures from Baseline | 29.7 percentage of participants |
| Placebo | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 50% or More in Drop Seizures from Baseline | 16.2 percentage of participants |
| Placebo | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 75% or More in Drop Seizures from Baseline | 2.7 percentage of participants |
| Placebo | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 100% in Drop Seizures from Baseline | 0 percentage of participants |
| TAK-935 | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 100% in Drop Seizures from Baseline | 5.0 percentage of participants |
| TAK-935 | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 25% or More in Drop Seizures from Baseline | 42.5 percentage of participants |
| TAK-935 | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 75% or More in Drop Seizures from Baseline | 10.0 percentage of participants |
| TAK-935 | Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period | Reduction of 50% or More in Drop Seizures from Baseline | 27.5 percentage of participants |
Secondary
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period
Convulsive seizure frequency per 28 days is defined as 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 (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement.
Time frame: Baseline; Maintenance Period: Weeks 9 to 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is 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 in Participants With Dravet Syndrome Stratum During the Maintenance Period | 9.38 percent change |
| TAK-935 | Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period | -36.50 percent change |
p-value: 0.000195% CI: [-75.03, -25.09]Ranked ANCOVA
Secondary
Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period
Drop seizure frequency per 28 days is defined as total number of drop seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement.
Time frame: Baseline; Maintenance Period: Weeks 9 to 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period | -1.90 percent change |
| TAK-935 | Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period | -18.46 percent change |
p-value: 0.14795% CI: [-39.5, 4.49]Ranked ANCOVA
Secondary
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period
Seizure Frequency per 28 days is defined as total number of Seizures reported (convulsive seizures for DS, drop seizures for LGS) during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during treatment period - frequency of seizures per 28 days at baseline) divided by frequency of seizures per 28 days at baseline multiplied by 100. Negative percent change from Baseline indicates improvement.
Time frame: Baseline; Treatment Period: Weeks 0 to 20
Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period | 0.75 percent change |
| TAK-935 | Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period | -30.05 percent change |
p-value: 0.002495% CI: [-43.96, -10.69]Ranked ANCOVA