Study of TAK-935 as an Adjunctive Therapy in Participants With Developmental and/or Epileptic Encephalopathies

NCT03166215 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-935-2001U1111-1192-7890
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to characterize the multiple-dose safety and tolerability profile of TAK-935 in adult participants with developmental and/or epileptic encephalopathies.

Conditions

Developmental and/or Epileptic Encephalopathies

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), as Reported by the Participants or Participant's Caregivers or Observed by the Investigator, After TAK-935 Treatment

  An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug

  From first dose up to 30 days post last dose (approximately up to 120 days)

Secondary Outcomes (10)

• Drug Clearance (CL) and Intercompartmental Clearance (Q) for TAK-935 Calculated Using the Observed Value of the Last Quantifiable Concentration

  Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose

• Apparent Volume of Distribution (Vz/F) of Central Compartment (Vc) and Peripheral Compartment (Vp) for TAK-935 Calculated Using the Observed Value of the Last Quantifiable Concentration

  Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose

• Absorption Rate Constant (Ka) for TAK-935

  Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose

• Cmax,ss: Maximum Observed Plasma Concentration for TAK-935 at Steady State

  Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose

• AUC0-tau,ss: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-935 at Steady State

  Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose

Study Arms (3)

Part 1: Placebo

PLACEBO COMPARATOR

TAK-935 matching-placebo tablets, orally or through gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, twice daily (BID) from Days 1 to 30 in dose titration period.

Drug: TAK-935

Part 1: TAK-935

EXPERIMENTAL

TAK-935 100 mg, tablet, orally or through G-tube/PEG tube, BID from Days 1 to 10 followed by TAK-935 100 mg tablets x2, orally or through G-tube/PEG tube, BID from Days 11 to 20 followed by TAK-935 100 mg tablets x3, orally or through G-tube/PEG tube, BID from Days 21 to 30 in dose titration period. The dose of TAK-935 was escalated or de-escalated during Part 1 as per investigator's discretion.

Drug: Placebo

Part 2: TAK-935

EXPERIMENTAL

TAK-935 100 mg tablets x2, orally or through G-tube/PEG tube, BID from Days 31 to 40 followed by TAK-935 100 mg tablets x1, x2 or x3, orally or through G-tube/PEG tube, BID from Days 31 to Day 85 as per investigator's discretion in the maintenance period. At the end of Part 2, the dose of TAK-935 was de-escalated until discontinuation.

Drug: TAK-935

Interventions

TAK-935 DRUG

TAK-935 tablets.

Part 1: Placebo; Part 2: TAK-935

Placebo DRUG

TAK-935 placebo-matching tablets.

Part 1: TAK-935

Eligibility Criteria

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

You may qualify if:

• Has a documented clinical diagnosis of developmental and/or epileptic encephalopathies with countable bilateral motor seizures, defined as an average of greater than or equal to (\>=) 2 per month during the past 3 months, based on the investigator's assessment, and a monthly average of \>=1 per month during the Baseline Period, based on the seizure diary record.
• Has been taking 1 to 4 antiepileptic drug (AEDs) at a stable dose for \>=4 weeks before Screening and the participant or participant's legally acceptable representative is willing to keep the regimen(s) stable throughout the study.
• Has an average of \>=1 bilateral motor seizure per month during the 4-week Baseline Period (that is., drop seizures, tonic-clonic, tonic, bilateral clonic, atonic, myoclonic-atonic, myoclonic-tonic-clonic, focal seizures with bilateral hyperkinetic motor features).
• Must agree to not post any participant's personal medical data related to the study or information related to the study on any web site or social media site (example, Facebook, Twitter) until the study has been completed.
• For participants with G-tube/PEG tube, G-tubes/PEG tubes should have been placed and been functioning for at least 3 months prior to screening. Naso-gastric tubes are not allowed.

You may not qualify if:

• Has received TAK-935 in a previous clinical study or as a therapeutic agent.
• Was admitted to a medical facility for treatment of status epilepticus requiring mechanical respiration within 3 months before Screening.
• Had a vagal nerve stimulator implanted within 6 months before Screening and settings have been changed within 1 month of the Screening Visit and/or anticipated to change during the study.
• Is on ketogenic diet that has been started within 6 months of the Screening Visit, has been changed within 1 month of the Screening Visit, or is anticipated to change during the study.
• Has degenerative eye disease.
• Has a history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening. If the participant is unable to comply with the C-SSRS due to developmental status, a parent proxy may be used for the completion of the C-SSRS. The Investigator may also use clinical judgment, which must then be documented in the source document.
• Positive for human immunodeficiency virus, hepatitis B, or hepatitis C infections. (Note that participants who have been vaccinated against hepatitis B \[hepatitis B surface antibody (Ab)-positive\] who are negative for other markers of prior hepatitis B infection \[example, negative for hepatitis B core Ab\] are eligible. Also note that participants who are positive for hepatitis C Ab are eligible as long as they have a negative hepatitis C viral load by quantitative polymerase chain reaction \[qPCR\]).
• Has an abnormal and clinically significant ECG at Screening in the opinion of the investigator, for example, second or third degree heart block or a corrected QT interval (QTc) greater than (\>) 450 millisecond (msec). Entry of any participant with an abnormal but not clinically significant ECG must be approved and documented by signature by the principal investigator or appropriately qualified delegate.
• Has abnormal clinical laboratory test results at Screening that suggest a clinically significant underlying disease. If the participant has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>2.5\*the upper limit of normal (ULN), the Medical Monitor should be consulted.
• Has received any excluded medications, procedures, or treatments during the time periods.
• Has any a history of alcohol, opioid, or other drug use disorder, as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within the previous 2 years before Screening. Medical marijuana use is allowed.
• Has unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.

Sponsors & Collaborators

• Takeda: lead
• Healx AI: collaborator

Study Sites (11)

Xenoscience

Phoenix, Arizona, 85004, United States

Location

Medsol Clinical Research Center

Port Charlotte, Florida, 33952, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Center for Integrative Rare Disease Research

Atlanta, Georgia, 30318, United States

Location

Bluegrass Epilepsy Research

Lexington, Kentucky, 40504, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

The Comprehensive Epilepsy Care Center for Children and Adults

St Louis, Missouri, 63131, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Virginia Health Sciences Center

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Halford JJ, Sperling MR, Arkilo D, Asgharnejad M, Zinger C, Xu R, During M, French JA. A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies. Epilepsy Res. 2021 Aug;174:106646. doi: 10.1016/j.eplepsyres.2021.106646. Epub 2021 Apr 22.

  PMID: 33940389 DERIVED

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

877-825-3327

Study Officials

• Medical Monitor Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 25, 2017
• Study Start: August 17, 2017
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: January 7, 2021
• Results First Posted: January 10, 2020

Record last verified: 2020-12

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

US (11)