EpilepsyPhase 2Endymion 1NCT03635073
A Study of Soticlestat in Adults and Children With Rare Epilepsies
A Phase 2 study testing Soticlestat in people with Epilepsy and Dravet Syndrome (DS), run by Takeda at 59 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Epilepsy, Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS)
- What is being tested?
- Soticlestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 59 sitesin 8 countries
- Study dates
- 19 Jul 2018to 30 Jul 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
59 sites in 8 countries.
59 sites in 8 countries
United States27 sites
Rare Disease Research, LLC
Atlanta, Georgia, 30318
Rare Disease Research, LLC
Atlanta, Georgia, 30322
Colorado Children's Hospital
Aurora, Colorado, 80045-7106
Colorado Children's Hospital
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina Childrens Hospital - PIN
Charleston, South Carolina, 29425
Max Benzaquen, M.D., PC
Chesterfield, Missouri, 63017
Ann and Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois, 60611
Cook Children's Medical Center - Jane and John Justin Neurosciences Center
Fort Worth, Texas, 76104
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601-1974
Bluegrass Epilepsy Research LLC
Lexington, Kentucky, 40504
David Geffen School of Medicine at UCLA
Los Angeles, California, 900095-1752
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095-8358
Nicklaus Children's Hospital
Miami, Florida, 33155-3009
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital at Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
NYU - Ambulatory Care Center (ACC)
New York, New York, 10016
Columbia University Medical Center - PIN
New York, New York, 10032
Center for Rare Neurological Diseases
Norcross, Georgia, 30093
Xenosciences Inc
Phoenix, Arizona, 85004
Medsol Clinical Research Center Inc
Port Charlotte, Florida, 33952
Medsol Clinical Research Center Inc
Port Charlotte, Florida, 33980
Mayo Clinic - PIN
Rochester, Minnesota, 55905
Minnesota Epilepsy Group PA
Saint Paul, Minnesota, 55102
University of South Florida
Tampa, Florida, 33606
Wake Forest Baptist Medical Center - PPDS
Winston-Salem, North Carolina, 27157
Pediatric Neurology PA
Winter Park, Florida, 32789
Israel8 sites
Soroka University Medical Centre
Beersheba, 84101
Bnai Zion Medical Center
Haifa, 31048
Edith Wolfson Medical Center
Holon, 58100
Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
Petah Tikva, 49100
Sheba Medical Center - PPDS
Ramat Gan, 52621
Sheba Medical Center - PPDS
Ramat Gan, 5265601
Tel Aviv Sourasky Medical Center PPDS
Tel Aviv, Tel Aviv, 64239
Tel Aviv Sourasky Medical Center PPDS
Tel Aviv, 64239
China7 sites
Peking University First Hospital
Beijing, 100034
Beijing Children's Hospital,Capital Medical University
Beijing, 100045
Beijing Children's Hospital,Capital Medical University
Beijing, 100069
Xiangya Hospital Central South University
Changsha, 410008
Xiangya Hospital of Central South University
Changsha, 410008
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, 201102
Shenzhen Children's Hospital
Shenzhen, Guangdong, 518026
Poland5 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-952
NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
Kielce, Świętokrzyskie Voivodeship, 25-316
Centrum Medyczne Plejady
Krakow, 30-363
Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan, Greater Poland Voivodeship, 60-355
Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
Warsaw, 02-091
Spain5 sites
Hospital Vithas La Salud
Granada, 18008
Hospital Ruber Internacional (Grupo Quironsalud)
Madrid, Madrid, Communidad Delaware, 28034
Hospital Ruber Internacional (Grupo Quironsalud)
Madrid, 28034
Clinica Universidad Navarra
Pamplona, Navarre, 31008
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Australia3 sites
Monash Children's Hospital
Clayton, Victoria, 3168
Austin Hospital
Heidelberg, Victoria, 3084
Austin Hospital
Heidelberg West, Victoria, 3081
Portugal3 sites
Centro Hospitalar Lisboa Central- Hospital Dona Estefania
Lisbon, 1169-045
Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
Lisbon, 1600-035
Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
Lisbon, 1649-035
About this study
Official title: A Phase 2, Prospective, Interventional, Open-Label, Multi-Site, Extension Study to Assess the Long-Term Safety and Tolerability of Soticlestat (TAK-935) as Adjunctive Therapy in Subjects With Developmental Epileptic Encephalopathies Including Dravet Syndrome, Lennox Gastaut Syndrome, CDKL5 Deficiency Disorder, and Chromosome 15 Duplication Syndrome (ENDYMION 1)
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.
Read the detailed description
The drug being tested in this study is called soticlestat (TAK-935). This global, open-label extension (OLE) study will assess the long-term safety and tolerability of soticlestat in participants with developmental and epileptic encephalopathy (DEE) who participated in previous short-term efficacy/safety studies of soticlestat. All participants will receive Soticlestat treatment.
Participants who rollover from previous blinded study will undergo up to 2 weeks of Dose Optimization Period (depending on the previous study) followed by Maintenance Period. Participants who rollover from an open-label study will continue on their current dose until development is stopped by the sponsor, or the product is approved for marketing, or at any time at the discretion of the sponsor. There will be a 4-week Safety Follow-up Period after the last dose in Maintenance Period, including a 2-week dose Tapering Period.
- Being tested
- Soticlestat
- Keywords
- Soticlestat, Drug Therapy
- Medical subject headings
- Epilepsy, Epilepsies, Myoclonic, Lennox Gastaut Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SoticlestatDrug
Also called TAK-935
Soticlestat tablets or mini-tablets.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Soticlestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 338
Change From Baseline in Vital Signs: Heart Rate
Measured: Baseline, Week 338
Change From Baseline in Vital Signs: Respiratory Rate
Measured: Baseline, Week 338
Change From Baseline in Vital Signs: Temperature
Measured: Baseline, Week 338
Change From Baseline in Body Weight
Measured: Baseline, Week 338
Change From Baseline in Electrocardiogram (ECG) Parameters: ECG Heart Rate
Measured: Baseline, Week 338
Change From Baseline in ECG Parameters: PR Interval
Measured: Baseline, Week 338
Change From Baseline in ECG Parameters: QRS Duration
Measured: Baseline, Week 338
Change From Baseline in ECG Parameters: QT Interval
Measured: Baseline, Week 338
Change From Baseline in ECG Parameters: QTcF Interval
Measured: Baseline, Week 338
Change From Baseline in ECG Parameters: RR Interval
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 338
Number of Participants With Potentially Clinically Significant ECG Evaluations
Measured: Baseline to Week 338
Secondary outcomes (5)
Percent Change From Baseline in All Seizure 28-day Frequency
Change from Baseline is denoted as CFB.
Measured: Baseline, Week 252
Percent Change From Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut Syndrome [LGS] Participants)
Change from Baseline is denoted as CFB.
Measured: Baseline, Week 252
Percent Change From Baseline in Convulsive Seizure 28-day Frequency (Dravet Syndrome [DS] Participants)
Change from Baseline is denoted as CFB.
Measured: Baseline, Week 252
Percent Change From Baseline in Motor Seizure 28-day Frequency
Measured: Baseline, Week 252
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S)
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.
Measured: Baseline, Week 336
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start19 Jul 2018
- Primary completion30 Jul 2025
- Study completion30 Jul 2025
Why it stopped: Due to negative results from phase 3 SKYLINE and SKYWAY studies and unrelated to patient safety it has been determined that supplementary data from TAK-935-18-001 study is no longer necessary. Therefore, Takeda has made a decision to close this study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda (Note: This product was divested to Mistrau Bio, Inc. in 2026)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03635073
- Sponsor's protocol ID
- TAK-935-18-001
- Other IDs
- U1111-1218-5515, 2018-002485-39, 2022-502801-13-00, 2018
- Acronym
- Endymion 1
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2018
- Last updated
- 4 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.