Trial Outcomes & Findings for A Study of Soticlestat in Adults and Children With Rare Epilepsies (NCT NCT03635073)

NCT ID: NCT03635073

Last Updated: 2026-03-19

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

156 participants

Primary outcome timeframe

Baseline, Week 338

Results posted on

2026-03-19

Participant Flow

Participants took part in the study at 42 investigative sites globally from 19 July 2018 to 30 July 2025.

Paediatric (ages ≥6 to \<18 years) and adult participants (≥18 years) with developmental and epileptic encephalopathies who participated in antecedent studies of Soticlestat (TAK-935-2001\[NCT03166215\], TAK-935-2002 (ELEKTRA) \[NCT03650452\] and TAK-935-18-002 (ARCADE) \[NCT03694275\]) were enrolled in this open-label extension (OLE) study.

Participant milestones

Participant milestones
Measure	Soticlestat Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Overall Study STARTED	156
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	156

Reasons for withdrawal

Reasons for withdrawal
Measure	Soticlestat Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Overall Study Greater than 100% increase in 28-day seizure frequency	2
Overall Study Enrollment in other Clinical Study	1
Overall Study Physician Decision	3
Overall Study Withdrawal by Parent/Guardian	19
Overall Study Sponsor Decision	50
Overall Study Adverse Event	18
Overall Study Lack of Efficacy	56
Overall Study Lost to Follow-up	2
Overall Study Reason Not Specified	5

Baseline Characteristics

A Study of Soticlestat in Adults and Children With Rare Epilepsies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Age, Continuous	10.4 years STANDARD_DEVIATION 5.92 • n=110 Participants
Sex: Female, Male Female	60 Participants n=110 Participants
Sex: Female, Male Male	96 Participants n=110 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=110 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	135 Participants n=110 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=110 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=110 Participants
Race (NIH/OMB) Asian	44 Participants n=110 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=110 Participants
Race (NIH/OMB) Black or African American	2 Participants n=110 Participants
Race (NIH/OMB) White	109 Participants n=110 Participants
Race (NIH/OMB) More than one race	0 Participants n=110 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=110 Participants

PRIMARY outcome

Timeframe: From screening up to end of the study (up to approximately 84 months)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication.

An Adverse Event (AE) was defined any untoward medical occurrence in a subject or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign vital sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to this medicinal product. A TEAE is defined as any AE that starts or increases in severity during or after the first dose of study drug.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Percentage of Participants Who Experienced At Least One Treatment-emergent Adverse Event (AE)	91.0 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time points. Baseline is denoted as BL, change from baseline as CFB and Week as W for the reported categories.

VABS,3rd edition,Parent Caregiver Form:parent-report questionnaire of adaptive functioning/how is individual's routine behaviour at home \& in community.4 domains(Communication,Daily Living,Social Skills\&Relationships,Problem Behaviors) contained 12 subdomains including items(each scored 0-2).Subdomain scores=sum of item scores within that subdomain.Ranges of subdomain scores are:Communication:Listening\&Understanding(0-78);Talking(0-98);Reading\&Writing(0-76),Daily Living:Caring for Self(0-110);Caring for Home(0-60);Living in Community(0-116),Social Skills\&Relationships:Relating to Others(0-86);Playing\&Using Leisure Time(0-72);Adapting(0-66),Problem Behaviors:Section A(0-26);Section B(0-22),Section C(0-40).For 1st 3 domains,higher subdomain scores=higher adaptive functioning,positive CFB=improvement.For Problem Behaviors,higher subdomain scores=more problem behaviors,negative CFB=improvement(reduction in problem behaviors).No subdomain scores combined to compute any total score.

Outcome measures

Outcome measures
Measure	Soticlestat n=154 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Communication: Reading And Writing	-5.5 score on a scale Standard Deviation 2.12	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Daily Living: Caring For Self	35.1 score on a scale Standard Deviation 27.52	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Daily Living: Caring For Self	-1.5 score on a scale Standard Deviation 13.44	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Daily Living: Caring For Home	-5.0 score on a scale Standard Deviation 10.39	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Social Skills And Relationship: Relating To Others	7.0 score on a scale Standard Deviation 15.62	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Social Skills And Relationship: Playing And Using Leisure Time	21.0 score on a scale Standard Deviation 4.00	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Social Skills And Relationship: Adapting	15.0 score on a scale Standard Deviation 11.97	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Social Skills And Relationship: Adapting	11.3 score on a scale Standard Deviation 8.14	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Problem Behaviors: Section B	4.3 score on a scale Standard Deviation 3.82	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Problem Behaviors: Section B	-5.7 score on a scale Standard Deviation 1.15	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Problem Behaviors: Section C	5.6 score on a scale Standard Deviation 4.49	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Communication: Listening And Understanding	32.3 score on a scale Standard Deviation 21.64	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Communication: Listening And Understanding	0.7 score on a scale Standard Deviation 0.58	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Communication: Talking	33.5 score on a scale Standard Deviation 29.19	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Communication: Talking	-3.0 score on a scale Standard Deviation 2.83	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Communication: Reading And Writing	12.3 score on a scale Standard Deviation 15.89	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Problem Behaviors: Section C	-3.0 score on a scale Standard Deviation 6.08	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Daily Living: Caring For Home	11.1 score on a scale Standard Deviation 10.63	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Daily Living: Living In Community	14.9 score on a scale Standard Deviation 17.31	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Daily Living: Living In Community	-0.5 score on a scale Standard Deviation 9.19	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Social Skills And Relationship: Relating To Others	26.5 score on a scale Standard Deviation 16.68	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Social Skills And Relationship: Playing And Using Leisure Time	15.6 score on a scale Standard Deviation 14.18	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) BL: Problem Behaviors: Section A	5.5 score on a scale Standard Deviation 3.70	—
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) CFB at W 338: Problem Behaviors: Section A	-2.7 score on a scale Standard Deviation 5.13	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Number analyzed is the number of participants with data available for analysis at the specified time points.

The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items); Lethargy/Social Withdrawal subscale (16 items); Stereotypic Behavior subscale (7 items); Hyperactivity subscale (16 items); and Inappropriate Speech subscale (4 items). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). The total score was calculated by summing the scores on all 58 items where the total scores ranged from 0 to 174. Higher scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline scores represents improvement. Positive change from baseline scores represents worsening.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Behavior Measures Using Total Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age Baseline	36.8 score on a scale Standard Deviation 26.11	—
Change From Baseline in Behavior Measures Using Total Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age Change from Baseline at Week 338	-16.3 score on a scale Standard Deviation 8.50	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication.

The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items: Ranges from 0 to 45); Lethargy/Social Withdrawal subscale (16 items: Ranges from 0 to 48); Stereotypic Behavior subscale (7 items: Ranges from 0 to 21); Hyperactivity subscale (16 items: Ranges from 0 to 48); and Inappropriate Speech subscale (4 items: Ranges from 0 to 12). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). Subscale scores are calculated as the sum of items within the subscale. Higher subscale scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline score represents improvement. Positive change from baseline score represents worsening.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age BL: Hyperactivity	13.6 score on a scale Standard Deviation 10.23	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age CFB at W338: Hyperactivity	-3.0 score on a scale Standard Deviation 1.73	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age BL: Inappropriate Speech	1.8 score on a scale Standard Deviation 2.34	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age CFB at W338: Inappropriate Speech	-0.7 score on a scale Standard Deviation 1.15	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age BL: Irritability	8.6 score on a scale Standard Deviation 8.14	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age BL: Lethargy/Social Withdrawal	9.0 score on a scale Standard Deviation 7.78	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age CFB at W338: Lethargy/Social Withdrawal	-2.0 score on a scale Standard Deviation 1.00	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age BL: Stereotypic Behavior	3.9 score on a scale Standard Deviation 4.12	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age CFB at W338: Stereotypic Behavior	-3.3 score on a scale Standard Deviation 3.51	—
Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age CFB at W338: Irritability	-7.3 score on a scale Standard Deviation 4.93	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Only participants with change from baseline in C-SSRS are included in the categories.

Suicidal ideation and behavior was assessed in participants with at least 6 years of age using the C-SSRS. The C-SSRS is a 3-part scale that measures suicidal ideation (eg, participants endorses thoughts about a wish to be dead or has other thoughts of suicide), intensity of ideation (frequency), and suicidal behavior (actually, interrupted, and aborted attempts at suicide). SI=Suicidal Ideation; SB=Suicidal Behavior and NSSJB=Non-suicidal Self-injurious Behavior for the categories reported. BL denotes Baseline, V denotes Visit and W denotes Week in the categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL;V1: No SI or SB or NSSJB	83 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB; V1: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: No SI or SB or NSSJB; V2 W1: NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB; V2 W1: No SI or SB or NSSJB	2 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL;V5 W24: No SI or SB or NSSJB	40 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V5 W24: No SI or SB or NSSJB	4 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V7 W48: No SI or SB or NSSJB	48 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V9 W78: No SI or SB or NSSJB	7 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V16 W182: No SI or SB or NSSJB	38 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V17 W208: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V18 W234: No SI or SB or NSSJB	14 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V19 W260: No SI or SB or NSSJB	19 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V19 W260: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V22 W338: No SI or SB or NSSJB	3 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V7 W48: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V7 W48: No SI or SB or NSSJB	8 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V9 W78: No SI or SB or NSSJB	31 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V1: No SI or SB or NSSJB	8 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL;V2 W1: No SI or SB or NSSJB	11 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V9 W78: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V11 W104: No SI or SB or NSSJB	39 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V11 W104: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V11 W104: No SI or SB or NSSJB	15 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V13 W130: No SI or SB or NSSJB	37 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V13 W130: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V13 W130: No SI or SB or NSSJB	12 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V15 W156: No SI or SB or NSSJB	39 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V15 W156: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V15 W156: No SI or SB or NSSJB	12 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V16 W182: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V16 W182: No SI or SB or NSSJB	14 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V17 W208: No SI or SB or NSSJB	32 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V17 W208: No SI or SB or NSSJB	13 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V18 W234: No SI or SB or NSSJB	31 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: NSSJB;V18 W234: No SI or SB or NSSJB	1 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL: Missing;V19 W260: No SI or SB or NSSJB	9 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V20 W286: No SI or SB or NSSJB	6 Participants	—
Number of Participants With Changes From Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of Age BL,V21 W312: No SI or SB or NSSJB	5 Participants	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L)) BL: Albumin	45.7 g/L Standard Deviation 3.09	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L)) CFB at W 338: Protein	0.0 g/L Standard Deviation 2.65	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L)) BL: Protein	71.0 g/L Standard Deviation 4.95	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L)) CFB at W 338: Albumin	0.7 g/L Standard Deviation 1.53	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) BL: Alkaline Phosphatase	192.0 U/L Standard Deviation 85.64	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) CFB at W 338: Alkaline Phosphatase	8.3 U/L Standard Deviation 29.50	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) CFB at W 338: Alanine Aminotransferase	1.7 U/L Standard Deviation 9.87	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) BL: Aspartate Aminotransferase	25.1 U/L Standard Deviation 12.29	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) CFB at W 338: Aspartate Aminotransferase	-0.3 U/L Standard Deviation 6.66	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) BL: Creatine Kinase	116.1 U/L Standard Deviation 95.78	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) CFB at W 338: Creatine Kinase	-48.0 U/L Standard Deviation 78.08	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) BL: Gamma Glutamyl Transferase	33.4 U/L Standard Deviation 42.74	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) CFB at W 338: Gamma Glutamyl Transferase	5.0 U/L Standard Deviation 41.90	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) BL: Alanine Aminotransferase	16.3 U/L Standard Deviation 11.73	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L)) BL: Bilirubin	3.8093 µmol/L Standard Deviation 2.16765	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L)) CFB at W 338: Bilirubin	-1.7000 µmol/L Standard Deviation 3.2078	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L)) BL: Creatinine	33.3 µmol/L Standard Deviation 15.85	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L)) CFB at W 338: Creatinine	12.0 µmol/L Standard Deviation 13.75	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline, W denotes Week, HDL denotes High Density Lipid and LDL denotes Low Density Lipid for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Chloride	102.5 mmol/L Standard Deviation 3.81	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Cholesterol	0.69000 mmol/L Standard Deviation 0.4650	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Calcium	0.023 mmol/L Standard Deviation 0.1358	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Cholesterol	4.14622 mmol/L Standard Deviation 1.0682	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Chloride	0.7 mmol/L Standard Deviation 2.08	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Glucose	4.747 mmol/L Standard Deviation 0.7829	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Glucose	0.480 mmol/L Standard Deviation 1.0210	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: HDL Cholesterol	1.472 mmol/L Standard Deviation 0.3815	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: HDL Cholesterol	0.103 mmol/L Standard Deviation 0.1570	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Potassium	4.26 mmol/L Standard Deviation 0.333	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Potassium	-0.10 mmol/L Standard Deviation 0.458	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: LDL Cholesterol	2.275 mmol/L Standard Deviation 0.6286	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Sodium	-3.7 mmol/L Standard Deviation 2.08	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Triglycerides	1.122 mmol/L Standard Deviation 0.5604	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Calcium	2.414 mmol/L Standard Deviation 0.1048	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: LDL Cholesterol	0.543 mmol/L Standard Deviation 0.1419	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Sodium	140.0 mmol/L Standard Deviation 3.00	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Triglycerides	0.100 mmol/L Standard Deviation 1.0655	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) BL: Urea Nitrogen	4.233 mmol/L Standard Deviation 1.2945	—
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) CFB at W 338: Urea Nitrogen	1.190 mmol/L Standard Deviation 2.3223	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Overall number analyzed is the number of participants with data available for analysis at baseline. Number analyzed is the number of participants with data available for analysis at specified timepoints for specified category.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=152 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Neutrophils	-1.387 10^9 cells/L Standard Deviation 0.8292	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Platelets	252.8 10^9 cells/L Standard Deviation 87.09	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Platelets	-23.0 10^9 cells/L Standard Deviation 55.38	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Leukocytes	6.798 10^9 cells/L Standard Deviation 2.2816	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Leukocytes	-1.657 10^9 cells/L Standard Deviation 1.7827	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Eosinophils	0.136 10^9 cells/L Standard Deviation 0.1385	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Eosinophils	0.040 10^9 cells/L Standard Deviation 0.0265	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Lymphocytes	2.992 10^9 cells/L Standard Deviation 1.2962	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Lymphocytes	-0.157 10^9 cells/L Standard Deviation 1.1184	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Monocytes	0.588 10^9 cells/L Standard Deviation 0.2755	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Monocytes	-0.123 10^9 cells/L Standard Deviation 0.1012	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Neutrophils	3.033 10^9 cells/L Standard Deviation 1.4422	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) BL: Basophils	0.039 10^9 cells/L Standard Deviation 0.0266	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) CFB at W 338: Basophils	-0.020 10^9 cells/L Standard Deviation 0.0361	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Overall Number analyzed is the number of participants with data available for analysis at baseline. Number analyzed is the number of participants with data available for analysis at specified timepoints for specified category.

The percentage of the specified blood cells relative to total leukocyte count was determined and reported. BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=152 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) BL: Basophils/Leukocytes	0.58 % of cells Standard Deviation 0.339	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) CFB at W 338: Basophils/Leukocytes	-0.10 % of cells Standard Deviation 0.346	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) BL: Eosinophils/Leukocytes	1.99 % of cells Standard Deviation 1.783	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) CFB at W 338: Eosinophils/Leukocytes	0.73 % of cells Standard Deviation 0.551	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) BL: Lymphocytes/Leukocytes	44.48 % of cells Standard Deviation 12.090	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) CFB at W 338: Lymphocytes/Leukocytes	7.77 % of cells Standard Deviation 6.854	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) BL: Monocytes/Leukocytes	8.79 % of cells Standard Deviation 2.673	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) CFB at W 338: Monocytes/Leukocytes	-0.13 % of cells Standard Deviation 1.422	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) BL: Neutrophils/Leukocytes	44.09 % of cells Standard Deviation 12.357	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) CFB at W 338: Neutrophils/Leukocytes	-8.17 % of cells Standard Deviation 6.123	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=152 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Haematology (Liter Per Liter (L/L)) BL: Hematocrit	0.4018 L/L Standard Deviation 0.03889	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Liter Per Liter (L/L)) CFB at W 338: Hematocrit	-0.0320 L/L Standard Deviation 0.0376	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=152 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Haematology (Grams Per Liter (g/L)) BL: Hemoglobin	130.8 g/L Standard Deviation 13.24	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (Grams Per Liter (g/L)) CFB at W 338: Hemoglobin	1.7 g/L Standard Deviation 4.93	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=152 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^12 Cells Per Liter (10^12/L)) BL: Erythrocytes	4.458 10^12 cells/L Standard Deviation 0.4586	—
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^12 Cells Per Liter (10^12/L)) CFB at W 338: Erythrocytes	-0.070 10^12 cells/L Standard Deviation 0.0200	—

PRIMARY outcome

Timeframe: Baseline, Week 338

BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=155 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Vital Signs: Blood Pressure BL: Systolic Blood Pressure	107.7 millimeters of mercury (mmHg) Standard Deviation 12.63	—
Change From Baseline in Vital Signs: Blood Pressure BL: Diastolic Blood Pressure	66.6 millimeters of mercury (mmHg) Standard Deviation 9.93	—
Change From Baseline in Vital Signs: Blood Pressure CFB at W 338: Diastolic Blood Pressure	7.7 millimeters of mercury (mmHg) Standard Deviation 13.20	—
Change From Baseline in Vital Signs: Blood Pressure CFB at W 338: Systolic Blood Pressure	8.3 millimeters of mercury (mmHg) Standard Deviation 23.54	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Vital Signs: Heart Rate Baseline	95.0 beats per minute Standard Deviation 15.27	—
Change From Baseline in Vital Signs: Heart Rate Change from Baseline at Week 338	10.7 beats per minute Standard Deviation 12.01	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Vital Signs: Respiratory Rate Baseline	20.1 breaths per minute Standard Deviation 3.90	—
Change From Baseline in Vital Signs: Respiratory Rate Change from Baseline at Week 338	1.0 breaths per minute Standard Deviation 4.36	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Vital Signs: Temperature Baseline	36.4 degree Celsius (̊C) Standard Deviation 0.88	—
Change From Baseline in Vital Signs: Temperature Change from Baseline at Week 338	0.4 degree Celsius (̊C) Standard Deviation 0.55	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Body Weight Age <18: Baseline	33.1 kilograms (kg) Standard Deviation 15.69	—
Change From Baseline in Body Weight Age >=18: Baseline	76.3 kilograms (kg) Standard Deviation 23.61	—
Change From Baseline in Body Weight Age >=18: Change at Week 338	4.9 kilograms (kg) Standard Deviation 12.48	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=155 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Electrocardiogram (ECG) Parameters: ECG Heart Rate Baseline	94.0 beats per minute Standard Deviation 17.19	—
Change From Baseline in Electrocardiogram (ECG) Parameters: ECG Heart Rate Change from Baseline at Week 338	8.3 beats per minute Standard Deviation 14.50	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=155 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in ECG Parameters: PR Interval Baseline	131.5 milliseconds (msec) Standard Deviation 22.35	—
Change From Baseline in ECG Parameters: PR Interval Change from Baseline at Week 338	12.3 milliseconds (msec) Standard Deviation 10.12	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=154 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in ECG Parameters: QRS Duration Baseline	81.4 msec Standard Deviation 13.97	—
Change From Baseline in ECG Parameters: QRS Duration Change from Baseline at Week 338	-4.3 msec Standard Deviation 8.96	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=155 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in ECG Parameters: QT Interval Baseline	334.3 msec Standard Deviation 34.55	—
Change From Baseline in ECG Parameters: QT Interval Change from Baseline at Week 338	-13.0 msec Standard Deviation 20.07	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=155 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in ECG Parameters: QTcF Interval Baseline	387.9 msec Standard Deviation 26.09	—
Change From Baseline in ECG Parameters: QTcF Interval Change from Baseline at Week 338	-2.0 msec Standard Deviation 1.00	—

PRIMARY outcome

Timeframe: Baseline, Week 338

Outcome measures

Outcome measures
Measure	Soticlestat n=92 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in ECG Parameters: RR Interval Baseline	644.1 msec Standard Deviation 131.07	—
Change From Baseline in ECG Parameters: RR Interval Change from Baseline at Week 338	-9.5 msec Standard Deviation 95.46	—

PRIMARY outcome

Timeframe: Baseline to Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication.

ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, HGB: Hemoglobin, ULN: Upper limit of normal, LLN: Lower limit of normal and UREAN: Urea Nitrogen for the specified categories. mmol/L indicates millimoles per liter. Data is reported only for participants who had potentially clinically significant values.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values ALT or AST >5x ULN and Persists for >2 weeks	1 Participants	—
Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values ALT or AST >8x ULN	1 Participants	—
Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values HGB>1.2x ULN or HGB<0.8x LLN	3 Participants	—
Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values UREAN>10.7 mmol/L	1 Participants	—

PRIMARY outcome

Timeframe: Baseline to Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication.

Data is reported only for participants who had potentially clinically significant values.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Number of Participants With Potentially Clinically Significant Vital Signs High Systolic Blood Pressure	1 Participants	—
Number of Participants With Potentially Clinically Significant Vital Signs Low Systolic Blood Pressure	8 Participants	—
Number of Participants With Potentially Clinically Significant Vital Signs High Diastolic Blood Pressure	2 Participants	—
Number of Participants With Potentially Clinically Significant Vital Signs Low Diastolic Blood Pressure	12 Participants	—
Number of Participants With Potentially Clinically Significant Vital Signs High Heart Rate	19 Participants	—
Number of Participants With Potentially Clinically Significant Vital Signs Low Heart Rate	3 Participants	—

PRIMARY outcome

Timeframe: Baseline to Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication. Number of participants with height (in participants \< 18 years old) and weight (in participants \<= 10 years old) below -2SD of the median height or weight of the same age and gender per WHO growth chart have been reported.

The criteria for defining clinical significance for weight category was the participants less than equal to (\<=)10 years of age with weight below minus (-)2standard deviation (SD) of the median weight of the same age and gender per world health organization (WHO) growth chart and for height category was the participants less than (\<)18 years of age with height below -2SD of the median weight of the same age and gender per WHO growth chart.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Number of Participants With Potentially Clinically Significant Weight and Height Height	43 Participants	—
Number of Participants With Potentially Clinically Significant Weight and Height Weight	16 Participants	—

PRIMARY outcome

Timeframe: Baseline to Week 338

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of study medication.

Outcome measures

Outcome measures
Measure	Soticlestat n=156 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Number of Participants With Potentially Clinically Significant ECG Evaluations	1 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 252

Population: Modified Intent-to-Treat (mITT) Analysis Set included all enrolled participants who had received at least 1 dose of study drug and had been assessed for seizures for at least 1 day in the treatment period. Overall number analyzed is the number of participants with data available for analysis at the specified time point.

Change from Baseline is denoted as CFB.

Outcome measures

Outcome measures
Measure	Soticlestat n=35 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Percent Change From Baseline in All Seizure 28-day Frequency	-49.76 percent (%) of change Standard Deviation 64.120	—

SECONDARY outcome

Timeframe: Baseline, Week 252

Population: mITT Analysis Set included all enrolled participants who had received at least 1 dose of study drug and had been assessed for seizures for at least 1 day in the treatment period. Overall number of participants analyzed is the number of participants with LGS from the antecedent soticlestat study TAK-935-2002 with data available for analysis at the specified timepoints.

Change from Baseline is denoted as CFB.

Outcome measures

Outcome measures
Measure	Soticlestat n=10 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Percent Change From Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut Syndrome [LGS] Participants)	-12.20 % of change Standard Deviation 97.025	—

SECONDARY outcome

Timeframe: Baseline, Week 252

Population: mITT Analysis Set included all enrolled participants who had received at least 1 dose of study drug and had been assessed for seizures for at least 1 day in the treatment period. Overall number of participants analyzed is the number of participants with DS from the antecedent soticlestat study TAK-935-2002 with data available for analysis at the specified timepoint.

Change from Baseline is denoted as CFB.

Outcome measures

Outcome measures
Measure	Soticlestat n=10 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Percent Change From Baseline in Convulsive Seizure 28-day Frequency (Dravet Syndrome [DS] Participants)	-55.38 % of change Standard Deviation 48.295	—

SECONDARY outcome

Timeframe: Baseline, Week 252

Population: mITT Analysis Set: All enrolled participants who had received at least 1 dose of study drug and had been assessed for seizures for at least 1 day in the treatment period. Overall number of participants analyzed are the participants from antecedent study TAK-935-18-002 (NCT03694275) with with either chromosome 15q duplication (Dup 15q) or Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) with data available for analysis.

Outcome measures

Outcome measures
Measure	Soticlestat n=2 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD n=8 Participants Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Percent Change From Baseline in Motor Seizure 28-day Frequency	-48.81 percent of change Standard Deviation 72.399	-58.05 percent of change Standard Deviation 47.482

SECONDARY outcome

Timeframe: Baseline, Week 336

Population: mITT Analysis Set included all enrolled participants who had received at least 1 dose of study drug and had been assessed for seizures for at least 1 day in the treatment period. Only participants with change from baseline in CGI-S are included in the categories. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

CGI-S is used to obtain an assessment of symptom severity, focusing on clinicians' observations of the subject's current cognitive, functional, and behavioral performance. 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 (among the most severely ill participants). BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories.

Outcome measures

Outcome measures
Measure	Soticlestat n=149 Participants Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	TAK-935-18-002: CDD Participants from the antecedent soticlestat study TAK-935-18002 with CDD received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Borderline mentally ill	2 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Mildly ill	15 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Moderately ill	48 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Markedly ill	59 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Severely ill	23 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) BL: Among the most extremely ill	2 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) CFB at W 338: Normal, not at all ill	1 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) CFB at W 338: Borderline mentally ill	1 Participants	—
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) CFB at W 338: Mildly ill	1 Participants	—

Adverse Events

Soticlestat

Serious events: 43 serious events

Other events: 120 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Soticlestat n=156 participants at risk Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Infections and infestations Pneumonia aspiration	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia bacterial	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia mycoplasmal	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia viral	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Adenovirus infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Agitation	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Anger	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Ataxia	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Bacterial tracheitis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Brain injury	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Breakthrough COVID-19	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchiolitis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Coordination abnormal	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Craniocerebral injury	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Depressed level of consciousness	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Congenital, familial and genetic disorders Developmental hip dysplasia	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Enterovirus infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Epilepsy	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Escherichia urinary tract infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Febrile convulsion	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Feeding disorder	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fibula fracture	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
General disorders General physical health deterioration	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Generalised tonic-clonic seizure	2.6% 4/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gingival bleeding	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Hemiclonic seizure	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Hip fracture	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Ketosis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Investigations Liver function test increased	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
General disorders Pain	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Parainfluenzae virus infection	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Partial seizures	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	3.8% 6/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post procedural complication	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory syncytial virus bronchiolitis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory syncytial virus infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory tract infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Restrictive pulmonary disease	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Rhinovirus infection	1.9% 3/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	6.4% 10/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Seizure cluster	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	1.9% 3/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Shunt infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Staphylococcal infection	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Status epilepticus	3.8% 6/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
General disorders Sudden unexplained death in epilepsy	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Tonic convulsion	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	1.3% 2/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection enterococcal	0.64% 1/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	1.9% 3/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Soticlestat n=156 participants at risk Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.
Gastrointestinal disorders Vomiting	9.6% 15/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	13.5% 21/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	10.3% 16/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	13.5% 21/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	10.3% 16/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
General disorders Fatigue	6.4% 10/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	5.1% 8/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	9.0% 14/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Irritability	5.8% 9/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	15.4% 24/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	5.1% 8/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	21.8% 34/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	23.1% 36/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	9.0% 14/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	26.9% 42/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	6.4% 10/156 • From screening up to end of the study (up to approximately 84 months) Safety Population included all participants who received at least 1 dose of study drug.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place