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

NCT ID: NCT03166215

Last Updated: 2021-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-17
• Study Completion Date: 2018-09-19

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.

Detailed Description

The drug being tested in this study is called TAK-935. TAK-935 is being tested to treat people who have developmental and/or epileptic encephalopathies. This study will look at safety, tolerability and pharmacokinetics of people who take TAK-935. Study drug will be administered in a double-blind manner in Part 1 and in an open-label manner in Part 2.

The study will enroll approximately 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in Part 1-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• TAK-935
• Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

Participants will receive placebo or 100 milligram (mg) TAK-935 tablets, orally or through stable G-tube/PEG tube, BID, in Part 1 (Day 1) and dose will be increased to 200 mg (Day 11) BID and to 300 mg (Day 21) BID in dose titration period. All participants who complete the Double-Blind Treatment Period in Part 1 will have the option to continue directly into the Open-Label Treatment Period in Part 2 where they will receive TAK-935 as two 100 mg tablets (total dose is 200 mg TAK-935) orally or through G-tube/PEG tube, BID and dose will be increased to three 100 mg tablets (total dose is 300 mg TAK-935), orally, BID (Day 41). This dose level will be maintained until the final visit (Day 85) for the dose de-escalation phase.

This multi-center trial will be conducted in North America. The overall time to participate in this study is 121 days excluding screening period of 30-41 days. Participants will make multiple visits to the clinic, and a follow-up phone call will be conducted on Day 91 and at the end of the 30-day follow-up period (Day 121), participants will return to the clinic for a follow-up assessment.

Conditions

Developmental and/or Epileptic Encephalopathies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: Placebo

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.

Group Type: PLACEBO_COMPARATOR

TAK-935

Intervention Type: DRUG

TAK-935 tablets.

Part 1: TAK-935

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

TAK-935 placebo-matching tablets.

Part 2: TAK-935

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.

Group Type: EXPERIMENTAL

TAK-935

Intervention Type: DRUG

TAK-935 tablets.

Interventions

TAK-935

TAK-935 tablets.

Intervention Type: DRUG

Placebo

TAK-935 placebo-matching tablets.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. 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).

4. 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.

5. 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.

Exclusion Criteria

1. Has received TAK-935 in a previous clinical study or as a therapeutic agent.

2. Was admitted to a medical facility for treatment of status epilepticus requiring mechanical respiration within 3 months before Screening.

3. 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.

4. 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.

5. Has degenerative eye disease.

6. 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.

7. 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]).

8. 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.

9. 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.

10. Has received any excluded medications, procedures, or treatments during the time periods.

11. 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.

12. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Healx AI

INDUSTRY

Sponsor Role: collaborator

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Xenoscience

Phoenix, Arizona, United States

Medsol Clinical Research Center

Port Charlotte, Florida, United States

University of South Florida

Tampa, Florida, United States

Center for Integrative Rare Disease Research

Atlanta, Georgia, United States

Bluegrass Epilepsy Research

Lexington, Kentucky, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

The Comprehensive Epilepsy Care Center for Children and Adults

St Louis, Missouri, United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Virginia Health Sciences Center

Charlottesville, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33940389 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1192-7890

Identifier Type: OTHER

Identifier Source: secondary_id

TAK-935-2001

Identifier Type: -

Identifier Source: org_study_id