Trial Outcomes & Findings for A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies (NCT NCT03650452)

Last Updated: 2021-02-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

141 participants

Primary outcome timeframe

Baseline; Maintenance Period: Weeks 9 to 20

Results posted on

2021-02-18

Participant Flow

Participants took part in the study at 45 investigative sites globally from 8 August 2018 to 20 July 2020.

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).

Participant milestones

Participant milestones
Measure	Placebo TAK-935 placebo-matching tablets, orally or via gastrostomy tube (G-tube)/percutaneous endoscopic gastrostomy (PEG), twice a day (BID) up to Week 20.	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.
Overall Study STARTED	70	71
Overall Study COMPLETED	60	66
Overall Study NOT COMPLETED	10	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TAK-935 placebo-matching tablets, orally or via gastrostomy tube (G-tube)/percutaneous endoscopic gastrostomy (PEG), twice a day (BID) up to Week 20.	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.
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Parent/Guardian	3	1
Overall Study Adverse Event	3	4
Overall Study Early Withdrawal from Study Treatment	3	0

Baseline Characteristics

Number analyzed are the number of participants with data available for height at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=70 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=71 Participants 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.	Total n=141 Participants Total of all reporting groups
Age, Continuous	9.5 years STANDARD_DEVIATION 3.93 • n=70 Participants	9.6 years STANDARD_DEVIATION 4.14 • n=71 Participants	9.5 years STANDARD_DEVIATION 4.02 • n=141 Participants
Sex: Female, Male Female	28 Participants n=70 Participants	22 Participants n=71 Participants	50 Participants n=141 Participants
Sex: Female, Male Male	42 Participants n=70 Participants	49 Participants n=71 Participants	91 Participants n=141 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=70 Participants	11 Participants n=71 Participants	21 Participants n=141 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=70 Participants	60 Participants n=71 Participants	120 Participants n=141 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=70 Participants	0 Participants n=71 Participants	0 Participants n=141 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=70 Participants	0 Participants n=71 Participants	0 Participants n=141 Participants
Race (NIH/OMB) Asian	22 Participants n=70 Participants	22 Participants n=71 Participants	44 Participants n=141 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=70 Participants	0 Participants n=71 Participants	0 Participants n=141 Participants
Race (NIH/OMB) Black or African American	1 Participants n=70 Participants	0 Participants n=71 Participants	1 Participants n=141 Participants
Race (NIH/OMB) White	47 Participants n=70 Participants	49 Participants n=71 Participants	96 Participants n=141 Participants
Race (NIH/OMB) More than one race	0 Participants n=70 Participants	0 Participants n=71 Participants	0 Participants n=141 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=70 Participants	0 Participants n=71 Participants	0 Participants n=141 Participants
Region of Enrollment Australia	2 Participants n=70 Participants	2 Participants n=71 Participants	4 Participants n=141 Participants
Region of Enrollment Canada	3 Participants n=70 Participants	3 Participants n=71 Participants	6 Participants n=141 Participants
Region of Enrollment China	20 Participants n=70 Participants	21 Participants n=71 Participants	41 Participants n=141 Participants
Region of Enrollment Spain	11 Participants n=70 Participants	8 Participants n=71 Participants	19 Participants n=141 Participants
Region of Enrollment Israel	5 Participants n=70 Participants	4 Participants n=71 Participants	9 Participants n=141 Participants
Region of Enrollment Poland	12 Participants n=70 Participants	17 Participants n=71 Participants	29 Participants n=141 Participants
Region of Enrollment Portugal	2 Participants n=70 Participants	3 Participants n=71 Participants	5 Participants n=141 Participants
Region of Enrollment United States	15 Participants n=70 Participants	13 Participants n=71 Participants	28 Participants n=141 Participants
Height	132.4 cm STANDARD_DEVIATION 20.34 • n=68 Participants • Number analyzed are the number of participants with data available for height at Baseline.	134.7 cm STANDARD_DEVIATION 21.34 • n=71 Participants • Number analyzed are the number of participants with data available for height at Baseline.	133.6 cm STANDARD_DEVIATION 20.81 • n=139 Participants • Number analyzed are the number of participants with data available for height at Baseline.
Weight	32.8 kg STANDARD_DEVIATION 15.98 • n=70 Participants	33.3 kg STANDARD_DEVIATION 15.11 • n=71 Participants	33.0 kg STANDARD_DEVIATION 15.49 • n=141 Participants
Body Mass Index (BMI)	17.63 (kg/m^2) STANDARD_DEVIATION 4.378 • n=68 Participants • Number analyzed are the number of participants with data available for BMI at Baseline.	17.43 (kg/m^2) STANDARD_DEVIATION 4.048 • n=71 Participants • Number analyzed are the number of participants with data available for BMI at Baseline.	17.53 (kg/m^2) STANDARD_DEVIATION 4.198 • n=139 Participants • Number analyzed are the number of participants with data available for BMI at Baseline.
Clinical Global Impression of Severity (CGI-S) Responses of Investigator	4.8 score on a scale n=59 Participants • Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2.	4.5 score on a scale n=64 Participants • Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2.	4.65 score on a scale n=123 Participants • Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=56 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=64 Participants 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.
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period	3.11 percent change Interval -78.8 to 163.0	-27.76 percent change Interval -100.0 to 160.6

SECONDARY outcome

Timeframe: Baseline; Treatment Period: Weeks 0 to 20

Population: Efficacy Analysis Set included all mITT participants whose efficacy assessments were compliant with Protocol Amendment 2.

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.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=64 Participants 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.
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period	0.75 percent change Interval -60.1 to 437.8	-30.05 percent change Interval -100.0 to 347.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=24 Participants 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.
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 Interval -47.3 to 153.5	-36.50 percent change Interval -100.0 to 84.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=40 Participants 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.
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 Interval -78.8 to 163.0	-18.46 percent change Interval -100.0 to 160.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=40 Participants 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.
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 Interval 15.9 to 47.0	42.5 percentage of participants Interval 27.0 to 59.1
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 Interval 6.2 to 32.0	27.5 percentage of participants Interval 14.6 to 43.9
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 Interval 0.1 to 14.2	10.0 percentage of participants Interval 2.8 to 23.7
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 Interval 0.0 to 9.5	5.0 percentage of participants Interval 0.6 to 16.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=24 Participants 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.
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 Interval 0.0 to 15.4	20.8 percentage of participants Interval 7.1 to 42.2
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 Interval 0.0 to 15.4	8.3 percentage of participants Interval 1.0 to 27.0
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 Interval 2.9 to 34.9	66.7 percentage of participants Interval 44.7 to 84.4
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 Interval 0.0 to 15.4	41.7 percentage of participants Interval 22.1 to 63.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=58 Participants 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.
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	-0.2 score on scale Standard Deviation 0.14

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=58 Participants 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.
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	17.2 percentage of participants
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	15.5 percentage of participants
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	65.5 percentage of participants
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	0 percentage of participants
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	1.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=58 Participants 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.
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	13.8 percentage of participants
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	10.3 percentage of participants
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	32.8 percentage of participants
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	37.9 percentage of participants
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	3.4 percentage of participants
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	1.7 percentage of participants
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	0 percentage of participants

SECONDARY outcome

Timeframe: 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.

A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=61 Participants 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.
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	102.20 mg/dL Standard Deviation 62.332
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 Standard Deviation NA Standard deviation was not estimable for 1 participant.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=61 Participants 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.
Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy Baseline	31.00 seizures per 28 days Interval 3.1 to 1040.1	32.12 seizures per 28 days Interval 2.6 to 5187.7
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 Interval -84.9 to 520.4	-6.29 seizures per 28 days Interval -1024.3 to 77.7

Adverse Events

Placebo

Serious events: 13 serious events

Other events: 52 other events

Deaths: 0 deaths

TAK-935

Serious events: 11 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=70 participants at risk TAK-935 placebo-matching tablets, orally or via G-tube/PEG, BID up to Week 20.	TAK-935 n=71 participants at risk 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.
Infections and infestations Bronchiolitis	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Ear infection	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia viral	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Post procedural infection	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Respiratory syncytial virus bronchiolitis	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Septic shock	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	5.7% 4/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.8% 2/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Generalised tonic-clonic seizure	2.9% 2/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Seizure	2.9% 2/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.8% 2/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Seizure cluster	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Speech disorder	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Status epilepticus	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Tonic convulsion	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Feeding disorder	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Hiatus hernia	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Volvulus	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Foreign body in gastrointestinal tract	1.4% 1/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/70 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/71 • From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.