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A Study of a Drug to be Used in Addition With Another Drug to Treat Adults With Uncontrolled Partial-onset Seizures

Phase 4
Completed
Conditions
Epilepsy With Partial On-set Seizures
Interventions
Registration Number
NCT03116828
Lead Sponsor
Sumitomo Pharma America, Inc.
Brief Summary

A study of a drug to be used in addition with another drug to treat adults with Uncontrolled Partial-onset Seizures

Detailed Description

This is a 31-week, multicenter, 2-arm, prospective, open-label, non-randomized, Phase 4 study of eslicarbazepine acetate (ESL) as adjunctive therapy in adult subjects with a diagnosis of epilepsy with POS. Two groups of ESL-naïve subjects will be evaluated. The groups are defined as follows:

* Arm 1 (ESL as first add-on): This group will include subjects who have been maintained on a regimen consisting of a stable dose of LEV or LTG for at least 1 month (28 days) prior to screening and who have not used any adjunctive treatment.

* Arm 2 (ESL as later add-on): This group will include subjects who have been maintained on a regimen consisting of a stable dose of 1-2 AEDs (excluding oxcarbazepine \[OXC\]) for at least 1 month (28 days) prior to screening and who have used adjunctive treatment in the past.

The Arm 1 subjects will allow an assessment of the efficacy and safety of ESL in subjects who are early in the course of their disease and being treated with one of the most common first line AEDs.

The subjects in Arm 2 are similar to the subject population in the ESL Phase 3 adjunctive epilepsy studies, treatment-resistant subjects who are later in the course of their disease. The inclusion of these subjects in the present study will provide an assessment of the efficacy and safety of ESL as a later adjunctive therapy in a real world clinical setting.

In addition, this study will provide data from both Arm 1 and Arm 2 for several behavioral, mood-related, and QOL-related assessments that were not evaluated in the ESL Phase 3 adjunctive epilepsy program.

The study will consist of a Screening Phase of 1 to 2 weeks, followed by a 2-week Titration Phase, a 24-week Maintenance Phase, and a Safety Follow-up/Taper Phase of 4 weeks. The last visit in the Maintenance Phase (Visit 9) is considered the End of Study (EOS) visit

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
Inclusion Criteria
  1. Male or female subjects ≥ 18 years of age.

  2. Subject is willing and able to sign informed consent.

  3. Subject has a documented diagnosis of epilepsy with simple POS with a motor component or complex POS with or without secondarily generalized seizures as defined in the Classification of Seizures of the International League Against Epilepsy

  4. Subject has a documented electroencephalogram within 10 years prior to screening.

  5. Subject has had at least 3 POS during previous six months.

  6. Subject has had a sufficient number of seizures at time of enrollment to justify adjunctive therapy, as determined by the Investigator.

  7. Subjects are required to be ESL-naïve AND

    1. Maintained on a stable LEV or LTG regimen for at least 1 month (28 days) prior to screening with no history of adjunctive treatment (for Arm 1, ESL as first add-on).

      OR

    2. Maintained on a stable dose of 1-2 AEDs (excluding OXC) for at least 1 month (28 days) prior to screening and who have had prior adjunctive treatment (for Arm 2, ESL as later add-on).

  8. If the subject is treated with any stimulation device for epilepsy Vagal Nerve Stimulation (VNS), Responsive Neurostimulator (RNS), or similar, the device must have been implanted at least 6 months before screening and the device parameters must be documented as stable for at least 1 month prior to screening. (Note: These devices will not be counted as concomitant AED).

  9. Except for epilepsy, subject is judged to be in general good health based on medical history, physical examination findings, and clinical laboratory

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Exclusion Criteria
  1. Subjects with a prior exposure to ESL.

  2. Subjects currently being treated with OXC.

  3. Subject with a history of allergic reaction to OXC or CBZ, or a history of serious allergic reaction (Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms or similar) to any AED, or a history of serious allergic reactions to other medications.

  4. Subjects who have taken warfarin, felbamate, vigabatrin, or perampanel, (unless at stable dose with safety testing for ≥ 1 year) within a 4-week period prior to screening.

  5. Subjects taking ezogabine

    .

  6. Subject has taken any medication prohibited for this protocol within 4 weeks prior to Screening

  7. Subjects using benzodiazepines on more than an occasional basis (defined as more than 2 times per week), except when used chronically as an AED

  8. Seizure disorder characterized primarily by simple POS without motor signs.

  9. Subject has a history of primarily generalized seizures (eg, myoclonic, absence, tonic).

  10. Subject has a history of status epilepticus or cluster seizures (ie, 3 or more seizures within 30 minutes) within the 3 months prior to screening.

  11. Subject has had seizures of psychogenic origin or purely subjective seizures within the last 2 years.

  12. Subject has had seizures too close to count accurately.

  13. Subject has a known progressive structural central nervous system (CNS) lesion, progressive encephalopathy or any other condition that may result in epilepsy secondary to a cerebral abnormality.

  14. Subject whose current seizures are related to an acute medical illness or other non-epileptic origin.

  15. Subjects of Asian ancestry will be excluded if they are carriers of HLA-B*1502. Either:

    1. Subject must give written informed consent for genotyping, and test negative. OR
    2. Subjects must provide documentation of prior testing confirming non-carrier status.
  16. Subject has a major medical illness other than epilepsy that would prevent safe participation in this study, at the discretion of the Investigator, including (but not limited to) cardiac disease, thyroid disease, hepatic or renal impairment, endocrine or metabolic disease, gastrointestinal disease, or hematologic disease. Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. If the effect of the condition in regard to the risk to the subject or to the study results is unclear, the Medical Monitor should be consulted.

  17. Subjects with clinically relevant laboratory abnormalities at screening (eg, sodium < 130 mEq/L, alanine transaminase (ALT) or aspartate transaminase (AST) > 2.0 times the upper limit of the normal, white blood cell [WBC] count < 3,000 cells/mm3, estimated creatinine clearance < 50 mL/min, or has values for thyroid testing (free triiodothyronine (T3), free thyroxine (T4), thyroid stimulating hormone [TSH]) indicating the presence of significant thyroid dysfunction.

  18. Subject has a history or presence of abnormal electrocardiogram (ECG), which in the Investigator's opinion is clinically significant or QT interval corrected for heart rate using the Fridericia method (QTcF) of ≥ 450 msec per screening ECG.

  19. Subject has second or third-degree atrioventricular block that is not corrected with a pacemaker.

  20. Subjects who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th edition text revision defined criteria for major depressive episode within the last 6 months. Subjects with mild, chronic depression without recent hospitalization who are being maintained on a stable dose of a single antidepressant are acceptable.

  21. Subject has an active suicidal plan or intent (in the Investigator's opinion) in the past 4 weeks prior to screening.

  22. Subject has a history of suicide attempt in the last 2 years prior to screening.

  23. Subject has other major psychiatric disorders.

  24. Subjects who are not able to complete the diary in the Investigator's opinion.

  25. Subject has a history of alcohol or substance abuse within 2 years prior to screening for study participation, or subjects currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner, which, in the opinion of the Investigator, indicates abuse.

  26. Subject tests positive for drugs of abuse at screening. Note: Subjects with a positive drug screen for marijuana, amphetamines, opiates, or benzodiazepines, who have a documented prescription for a medical condition and are on a stable dose of this prescribed medication for at least 4 weeks prior to screening, may be eligible to participate in the study upon approval from the Medical Monitor.

  27. Subject is pregnant, currently nursing, or intends to become pregnant during the study period or within 30 days of the last dose of study drug.

  28. Subject has participated in any investigational study within 30 days prior to screening, as documented in subject's medical history.

  29. Subject is a clinical or investigational site staff member or relative of a staff member.

  30. Any other condition or circumstance that, in the opinion of the Investigator, may compromise the subject's ability to comply with the study protocol.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
eslicarbazepine acetate (arm 1)Eslicarbazepine Acetateeslicarbazepine acetate (as first add-on)mg/day as medically indicated at the discretion of Investigator up to a maximum dose of 1200 mg/day (Canadian sites) or 1600 mg/day (US sites)
eslicarbazepine acetate (arm 2)Eslicarbazepine Acetateeslicarbazepine acetate (as later add-on)
Primary Outcome Measures
NameTimeMethod
The Number of Subjects Completing 24 Weeks Adjunctive Therapy During Maintenance PhaseFrom the date of the first dose of the study drug until the completion of 24 weeks Maintenance Phase

Phase 4 study of eslicarbazepine acetate (ESL) as adjunctive therapy in adult subjects with a diagnosis of epilepsy with Partial-onset seizures (POS). Two groups of ESL-naïve subjects will be evaluated

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (55)

Temple University Lewis Katz School of Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

Aston Ambulatory Care Center

🇺🇸

Dallas, Texas, United States

Northwestern Medical Group, Deparment of Neurology

🇺🇸

Chicago, Illinois, United States

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

Vanderbilt Epilepsy Clinic

🇺🇸

Nashville, Tennessee, United States

University of Texas Health Science Center at San Antonio Medical Arts and Research Center

🇺🇸

San Antonio, Texas, United States

Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Clinical Research Center of NJ (CRCNJ)

🇺🇸

Voorhees, New Jersey, United States

University of South Alabaa Neurology Department

🇺🇸

Mobile, Alabama, United States

Altman Clinical and Translational Research Institute

🇺🇸

La Jolla, California, United States

Banner University Medical Center Phoenix=Neuroscience Institute

🇺🇸

Phoenix, Arizona, United States

Blue Sky Neurology, a Division of Carepoint PC

🇺🇸

Englewood, Colorado, United States

George Washington Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

University of Connecticut School of Mwdicine -UCONN Health

🇺🇸

Farmington, Connecticut, United States

Neurology Associates PA

🇺🇸

Maitland, Florida, United States

The Neurology Research Group, LLC

🇺🇸

Miami, Florida, United States

Laszlo J. Mate, MD, PA

🇺🇸

North Palm Beach, Florida, United States

Medsol Clinical Research Center

🇺🇸

Port Charlotte, Florida, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Minneapolis Clinic of Neurology

🇺🇸

Golden Valley, Minnesota, United States

Tallahassee Neurological Clinic

🇺🇸

Tallahassee, Florida, United States

Vero Beach Neurology And Reasearch Institue/The MS Center of Vero Beach

🇺🇸

Vero Beach, Florida, United States

Balijeet Shethi, MD

🇺🇸

Waldorf, Maryland, United States

Georgia Neurology and Sleep Medicine Associates

🇺🇸

Suwanee, Georgia, United States

Conslutants in Epilepsy & Neurology, PLLC

🇺🇸

Boise, Idaho, United States

Associates in Neurology, PSC

🇺🇸

Lexington, Kentucky, United States

Minnesota Epilepsy Group, PA

🇺🇸

Saint Paul, Minnesota, United States

Wayne State University/Detroit Medical Center

🇺🇸

Detroit, Michigan, United States

JFK Neuroscience Institute, JFK Medical Center

🇺🇸

Edison, New Jersey, United States

Austin Epilepsy Care Center

🇺🇸

Austin, Texas, United States

NYU Winthrop Hospital, Clinical Trials Center

🇺🇸

Mineola, New York, United States

Penn State Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

The Neurological Institute, PA

🇺🇸

Charlotte, North Carolina, United States

Providence Medical Group-Medford Neurology

🇺🇸

Medford, Oregon, United States

University of Cincinnati Medical Center

🇺🇸

Cincinnati, Ohio, United States

Drexel University

🇺🇸

Philadelphia, Pennsylvania, United States

Sooner Clinical Research

🇺🇸

Oklahoma City, Oklahoma, United States

SSM Health Dean Medical Group

🇺🇸

Madison, Wisconsin, United States

Londo Health Sciences Centre, University Hospital

🇨🇦

London, Ontario, Canada

University of Kentucky Hospital, Chandler Medical Center

🇺🇸

Lexington, Kentucky, United States

Boca Raton Regional Hospital, Marcus Neuroscience Institute

🇺🇸

Boca Raton, Florida, United States

Rancho Research Institute, Inc.

🇺🇸

Downey, California, United States

Neuro-Pain Medical Center

🇺🇸

Fresno, California, United States

University of California-Irvine

🇺🇸

Orange, California, United States

Infinity Clinical Research, LLC

🇺🇸

Hollywood, Florida, United States

Hawaii Pacific Neuroscience

🇺🇸

Honolulu, Hawaii, United States

Clinique D'Épilepsie Neuro Rive-Sud

🇨🇦

Greenfield Park, Quebec, Canada

Alleghany General Hospital (Allegheny Neurological Association)

🇺🇸

Pittsburgh, Pennsylvania, United States

Mid-Atlantic Epilepsy and Sleep Center

🇺🇸

Bethesda, Maryland, United States

UNC Inverstigal Drug Services

🇺🇸

Chapel Hill, North Carolina, United States

Neurological Services of Orlando, PA

🇺🇸

Orlando, Florida, United States

Pedicatric Neurology, PA

🇺🇸

Orlando, Florida, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Wake Forest Baptist Health Sciences, Department of Neurology

🇺🇸

Winston-Salem, North Carolina, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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