A Study of Soticlestat in Adults and Children With Rare Epilepsies

NCT03635073 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: TAK-935-18-001U1111-1218-55152018-002485-392022-502801-13-00
• Study Type: interventional
• Target: 156
• Locations: 8 countries
• Sites: 59

Brief Summary

The main aim is to assess the long-term safety and tolerability of soticlestat when used along with other anti-seizure treatment. Participants will receive soticlestat twice a day. Participants will visit the study clinic every 2-6 months throughout the study. Study treatments may continue as long as the participant is receiving benefit from it.

Conditions

Dravet Syndrome (DS); Lennox-Gastaut Syndrome (LGS); Epilepsy

Keywords

Soticlestat; Drug Therapy

Outcome Measures

Primary Outcomes (29)

• Percentage of Participants Who Experienced At Least One Treatment-emergent Adverse Event (AE)

  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.

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

• Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS)

  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.

  Baseline, Week 338

• 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

  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.

  Baseline, Week 338

• 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

  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.

  Baseline, Week 338

• 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

  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.

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L))

  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.

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells)

  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.

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Haematology (Liter Per Liter (L/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Haematology (Grams Per Liter (g/L))

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

  Baseline, Week 338

• Change From Baseline in Clinical Laboratory Parameters: Haematology (10^12 Cells Per Liter (10^12/L))

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

  Baseline, Week 338

• Change From Baseline in Vital Signs: Blood Pressure

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

  Baseline, Week 338

• Change From Baseline in Vital Signs: Heart Rate

  Baseline, Week 338

• Change From Baseline in Vital Signs: Respiratory Rate

  Baseline, Week 338

• Change From Baseline in Vital Signs: Temperature

  Baseline, Week 338

• Change From Baseline in Body Weight

  Baseline, Week 338

• Change From Baseline in Electrocardiogram (ECG) Parameters: ECG Heart Rate

  Baseline, Week 338

• Change From Baseline in ECG Parameters: PR Interval

  Baseline, Week 338

• Change From Baseline in ECG Parameters: QRS Duration

  Baseline, Week 338

• Change From Baseline in ECG Parameters: QT Interval

  Baseline, Week 338

• Change From Baseline in ECG Parameters: QTcF Interval

  Baseline, Week 338

• Change From Baseline in ECG Parameters: RR Interval

  Baseline, Week 338

• Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values

  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.

  Baseline to Week 338

• Number of Participants With Potentially Clinically Significant Vital Signs

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

  Baseline to Week 338

• Number of Participants With Potentially Clinically Significant Weight and Height

  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.

  Baseline to Week 338

• Number of Participants With Potentially Clinically Significant ECG Evaluations

  Baseline to Week 338

Secondary Outcomes (5)

• Percent Change From Baseline in All Seizure 28-day Frequency

  Baseline, Week 252

• Percent Change From Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut Syndrome [LGS] Participants)

  Baseline, Week 252

• Percent Change From Baseline in Convulsive Seizure 28-day Frequency (Dravet Syndrome [DS] Participants)

  Baseline, Week 252

• Percent Change From Baseline in Motor Seizure 28-day Frequency

  Baseline, Week 252

• Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S)

  Baseline, Week 336

Study Arms (1)

Soticlestat

EXPERIMENTAL

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.

Drug: Soticlestat

Interventions

Soticlestat DRUG

Soticlestat tablets or mini-tablets.

Also known as: TAK-935

Soticlestat

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have participated in a previous soticlestat study and meet one of the following conditions:
• Successfully completed a soticlestat clinical study.
• Received at least 10 weeks of treatment with the study drug in an antecedent placebo-controlled blinded soticlestat clinical study and the participant did not have a serious or severe AE that, in the investigator's or sponsor's opinion, was related to the study drug and would make it unsafe for the participant to continue receiving the study drug.
• In the opinion of the investigator, the participant has the potential to benefit from the administration of soticlestat

You may not qualify if:

• Clinically significant disease, that, in the investigator's opinion, precludes study participation.
• Enrollment in any other clinical trial involving an investigational drug, device, or treatment in the past 90 days (with the exception of an antecedent study involving Soticlestat).
• Participant is currently pregnant or breastfeeding or is planning to become pregnant during the study or within 30 days of the last study drug administration.
• Suicide attempt within the last year, at significant risk of suicide (either in the opinion of the investigator or defined as 'yes' to suicidal ideation question 4 or 5 on the C-SSRS at Screening) or appearing suicidal per investigator judgment.

Sponsors & Collaborators

• Takeda: lead

Study Sites (59)

Xenosciences Inc

Phoenix, Arizona, 85004, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 900095-1752, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-8358, United States

Location

Colorado Children's Hospital

Aurora, Colorado, 80045-7106, United States

Location

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155-3009, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Medsol Clinical Research Center Inc

Port Charlotte, Florida, 33952, United States

Location

Medsol Clinical Research Center Inc

Port Charlotte, Florida, 33980, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Pediatric Neurology PA

Winter Park, Florida, 32789, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30322, United States

Location

Center for Rare Neurological Diseases

Norcross, Georgia, 30093, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Bluegrass Epilepsy Research LLC

Lexington, Kentucky, 40504, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - PIN

Rochester, Minnesota, 55905, United States

Location

Minnesota Epilepsy Group PA

Saint Paul, Minnesota, 55102, United States

Location

Max Benzaquen, M.D., PC

Chesterfield, Missouri, 63017, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601-1974, United States

Location

Children's Hospital at Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

NYU - Ambulatory Care Center (ACC)

New York, New York, 10016, United States

Location

Columbia University Medical Center - PIN

New York, New York, 10032, United States

Location

Wake Forest Baptist Medical Center - PPDS

Winston-Salem, North Carolina, 27157, United States

Location

Medical University of South Carolina Childrens Hospital - PIN

Charleston, South Carolina, 29425, United States

Location

Cook Children's Medical Center - Jane and John Justin Neurosciences Center

Fort Worth, Texas, 76104, United States

Location

Monash Children's Hospital

Clayton, Victoria, 3168, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Austin Hospital

Heidelberg West, Victoria, 3081, Australia

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Shenzhen Children's Hospital

Shenzhen, Guangdong, 518026, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Children's Hospital,Capital Medical University

Beijing, 100045, China

Location

Beijing Children's Hospital,Capital Medical University

Beijing, 100069, China

Location

Xiangya Hospital Central South University

Changsha, 410008, China

Location

Xiangya Hospital of Central South University

Changsha, 410008, China

Location

Tel Aviv Sourasky Medical Center PPDS

Tel Aviv, Tel Aviv, 64239, Israel

Location

Soroka University Medical Centre

Beersheba, 84101, Israel

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Edith Wolfson Medical Center

Holon, 58100, Israel

Location

Schneider Children's Medical Center of Israel - Petah Tikvah - PIN

Petah Tikva, 49100, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, 52621, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center PPDS

Tel Aviv, 64239, Israel

Location

Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, Greater Poland Voivodeship, 60-355, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-363, Poland

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie

Warsaw, 02-091, Poland

Location

NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki

Kielce, Świętokrzyskie Voivodeship, 25-316, Poland

Location

Centro Hospitalar Lisboa Central- Hospital Dona Estefania

Lisbon, 1169-045, Portugal

Location

Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria

Lisbon, 1600-035, Portugal

Location

Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital Ruber Internacional (Grupo Quironsalud)

Madrid, Madrid, Communidad Delaware, 28034, Spain

Location

Clinica Universidad Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Vithas La Salud

Granada, 18008, Spain

Location

Hospital Ruber Internacional (Grupo Quironsalud)

Madrid, 28034, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Epilepsy; Epilepsies, Myoclonic; Lennox Gastaut Syndrome

Interventions

soticlestat

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

The study was terminated early based on Sponsor's decision.

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 17, 2018
• Study Start: July 19, 2018
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: March 19, 2026
• Results First Posted: March 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

ES (5); CA (1); CN (7); PL (5); IL (8); US (27); PT (3); AU (3)