Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs

NCT00866775 | Completed Phase 3 Results

• 1 other identifier: 093-045
• Study Type: interventional
• Target: 193
• Locations: 2 countries
• Sites: 106

Brief Summary

This is an 18-week, double-blind, multicenter study with gradual conversion from previous antiepileptic therapy to eslicarbazepine acetate monotherapy in subjects with partial epilepsy.

Conditions

Epilepsy With Simple or Complex Partial Onset Seizures

Keywords

Seizure; Epilepsy; Anticonvulsant; Historical Control; Monotherapy

Outcome Measures

Primary Outcomes (1)

• Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method

  Cumulative exit rate was defined as the proportion of subjects meeting at least one of the five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.

  Week 3 to Week 18

Secondary Outcomes (15)

• Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.

  Weeks 9 through 18

• Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.

  Weeks 15 through 18

• Completion Rate

  Week 1 to Week 18

• Completion Rate During the 10 Weeks of Monotherapy

  Weeks 8 through 18

• Time on Eslicarbazepine Acetate Monotherapy.

  Week 8 to Week 18

Study Arms (2)

Eslicarbazepine 1600 mg QD

EXPERIMENTAL

Subjects randomized to 1600 mg QD of eslicarbazepine acetate will titrate from 600 mg QD (Day 0) to 1200 mg QD (Week 1) to 1600 mg QD (Weeks 2-18) Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.

Drug: Eslicarbazepine acetate

Eslicarbazepine 1200 mg QD

EXPERIMENTAL

Subjects randomized to 1200 mg QD eslicarbazepine acetate will titrate from 400 mg QD (Day 0) to 800 mg QD (week 1) to 1200 mg QD (weeks 2-18) Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.

Drug: Eslicarbazepine acetate

Interventions

Eslicarbazepine acetate DRUG

1600 mg QD

Eslicarbazepine 1600 mg QD

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of partial epilepsy as defined in the Classification of Seizures of the International League Against Epilepsy (ILAE) (simple partial seizures with observable motor component, or complex, with or without secondary generalization) a. Medical history of seizures; b. Absence of confounding factors (pseudoseizures, syncope); c. Documented EEG recording (done within 5 years prior to screening) consistent with focal onset epilepsy.
• Documented CT or MRI scan conducted within 10 years prior to screening, showing the absence of a progressive structural abnormality (eg, tumor). Mesial temporal sclerosis is acceptable.
• ≥4 partial onset seizures during the 8 weeks prior screening with no 28-day seizure free period.
• Stable treatment with 1-2 AEDs during the last 4 weeks prior to screening.
• Subjects must have the ability to comprehend the informed consent form and be willing to provide informed consent. For subjects who are unable to comprehend the written consent, a witness/caregiver who is able to describe and provide an understanding of the informed consent to the subject must sign the consent form on behalf of the subject.
• Subjects must give written informed consent prior to participation in the study. For subjects \<18 years of age, the informed consent must be signed by the subject's parent or legal guardian, and, when appropriate and/or required by state or local law, minor subjects must give written informed assent prior to participation in the study. Subjects of Asian ancestry are required to give written informed consent for genotyping. All subjects must sign a HIPAA Form. All females of child bearing potential must also sign the "Women of Childbearing Potential" Addendum.
• A female subject is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); b. Child-bearing potential (all females ≤65 years of age), has a negative pregnancy test at screening and agrees to satisfy contraception requirements.

You may not qualify if:

• Subjects with only simple partial seizures without a motor component.
• Presence of generalized seizure syndromes (eg, juvenile myoclonic epilepsy or Lennox-Gastaut syndrome).
• History of pseudo-seizures.
• Current seizures related to an acute medical illness.
• Seizures secondary to metabolic, toxic or infectious disorder or drug abuse.
• Status epilepticus within 2 years prior to screening.
• Seizures only occurring in a cluster pattern.
• Subjects taking 2 of the following sodium channel blocking AEDs: phenytoin, carbamazepine, oxcarbazepine, or lamotrigine.
• Subjects taking 2 AEDs with both being in the upper dose range (defined as approximately two-thirds of the defined daily dose).
• Subjects taking more than 2 AEDs.
• Subjects with progressive structural central nervous system lesion or progressive encephalopathy.
• Subjects who have been on benzodiazepines, phenobarbital, or primidone on a regular basis within 3 months prior to screening.
• Subjects taking antipsychotics, tricyclic antidepressants, anxiolytics, sedative hypnotics including non-benzodiazepines, central opioid agonists/antagonists, monoamine oxidase inhibitors (MAOIs) within at least 5 half lives (or for at least 2 weeks whichever is longer) prior to randomization.
• Subjects presently on felbamate or vigabatrin
• Female subjects who are currently breastfeeding or intending to breastfeed during study period.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (106)

Norwood Neurology

Birmingham, Alabama, 35234, United States

Location

Greystone Neurology Center

Birmingham, Alabama, 35242, United States

Location

USA Neurology

Mobile, Alabama, 36693, United States

Location

Neurology Clinic, P.C.

Northport, Alabama, 35476, United States

Location

Clinical Research Consortium

Phoenix, Arizona, 85003, United States

Location

Clinical Research Consortium - Arizona

Phoenix, Arizona, 85004, United States

Location

Xenoscience Inc.

Phoenix, Arizona, 85004, United States

Location

Arizona Neurological Institute

Sun City, Arizona, 85351, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

K & S Professional Research Services

Little Rock, Arkansas, 72201, United States

Location

Sutter East Bay Medical Foundation

Berkley, California, 94705, United States

Location

Synergy Escondido

Escondido, California, 92025, United States

Location

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

Faculty of Physicians & Surgeons of Loma Linda University

Loma Linda, California, 92354, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

American Institute of Research

Los Gatos, California, 95032, United States

Location

Northridge Neurological Center

Northridge, California, 91325, United States

Location

Yafa Minazad, DO

Pasadena, California, 91105, United States

Location

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

American Institute of Research

Whittier, California, 90603, United States

Location

Anschutz Outpatient Pavilion

Aurora, Colorado, 80045, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Associated Neurologists, PC

Danbury, Connecticut, 06810, United States

Location

Bradenton Research Center, Inc.

Bradenton, Florida, 34205, United States

Location

Miami Clinical Research

Coral Gables, Florida, 33134, United States

Location

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Infiniti Clinical Research, LLC

Hollywood, Florida, 33021, United States

Location

University of Florida Health Science Center

Jacksonville, Florida, 32209, United States

Location

Neurology Associates, PA

Maitland, Florida, 32751, United States

Location

MIMA Century Research Associates

Melbourne, Florida, 32901, United States

Location

San Marcus Research Clinic

Miami, Florida, 33015, United States

Location

Neurosciences Consultants, LLC

Miami, Florida, 33176, United States

Location

Neurological Services Orlando

Orlando, Florida, 32806, United States

Location

Pediatric Neurolog, PA

Orlando, Florida, 32819, United States

Location

Neurology Associates of Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

Medsol Clinical Research Center

Port Charlotte, Florida, 33952, United States

Location

Tallahassee Neurological Clinic

Tallahassee, Florida, 32308, United States

Location

Pediatric Epilepsy & Neurology Specialists, PA

Tampa, Florida, 33609, United States

Location

Florida Comprehensive Epilepsy and Seizure Disorder Center

Tampa, Florida, 33613, United States

Location

Vero Neurology

Vero Beach, Florida, 32960, United States

Location

Palm Beach Clinical Research Network LLC

Wellington, Florida, 33414, United States

Location

Peachtree Neurological Clinic

Atlanta, Georgia, 30309, United States

Location

Emory University Department of Neurology

Atlanta, Georgia, 30322, United States

Location

PANDA Neurology and Atlanta Headache Specialists

Atlanta, Georgia, 30328, United States

Location

Harbin Clinic

Rome, Georgia, 30165, United States

Location

GA Neurology and Sleep Medicine Associates

Suwanee, Georgia, 30024, United States

Location

Consultants in Epilepsy and Neurology, PLLC.

Boise, Idaho, 83702, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

UCMC

Chicago, Illinois, 60637, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Southern Illinois University

Springfield, Illinois, 62702, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Bluegrass Epilepsy Research LLC

Lexington, Kentucky, 40504, United States

Location

North Oaks Neurology

Hammond, Louisiana, 70403, United States

Location

MMP Neurology

Scarborough, Maine, 04074, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Massachusetts General Hospital Epilepsy Service - WACC

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, 63017, United States

Location

PsychCare Consultants Research

St Louis, Missouri, 63128, United States

Location

Cooper University Health System

Camden, New Jersey, 08103, United States

Location

Cooper University Health System

Cherry Hill, New Jersey, 08034, United States

Location

NJ Neuroscience Center

Edison, New Jersey, 08818, United States

Location

Institute of Neurology and Neurosurgery at St. Bamabas, Suite 101

Livingston, New Jersey, 07039, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

University of Medicine and Dentistry of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

St. Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

Five Towns Neuroscience Research

Cedarhurst, New York, 11516, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Clinilabs Inc.

New York, New York, 10019, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

The Neurology Institute

Charlotte, North Carolina, 28204, United States

Location

PMG Research of Hickory, LLC

Hickory, North Carolina, 28602, United States

Location

Wake Forest University

Winstom-Salem, North Carolina, 27157, United States

Location

Northern Ohio Neurosciences

Bellevue, Ohio, 44811, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112', United States

Location

5929 N. May Ave.

Oklahoma City, Oklahoma, 73112, United States

Location

Providence Medical Group

Medford, Oregon, 97504, United States

Location

Children's Hospital Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Children's Hospital of Pittsburg of UPMC

Pittsburgh, Pennsylvania, 15201, United States

Location

Gus Stratton / Neurology

Cranston, Rhode Island, 02920, United States

Location

Mid-South Physcians Group

Germantown, Tennessee, 38138, United States

Location

Access Clinical Trials

Nashville, Tennessee, 37203, United States

Location

VU Department of Neurology

Nashville, Tennessee, 37232, United States

Location

Neurology Associates of Arlington, PA

Arlington, Texas, 76017, United States

Location

Texas Neurology, PA

Dallas, Texas, 75214, United States

Location

Neurological Clinic of Texas P.A.

Dallas, Texas, 75230, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UT Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Todd Swick, MD, PA

Houston, Texas, 77063, United States

Location

Neurology Associates of Arlington, PA

Mansfield, Texas, 76063, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

Sentara Neurology Specialists

Norfolk, Virginia, 23507, United States

Location

Neurological Associates of Washington/Clinical Trials of America Inc.

Bellevue, Washington, 98004, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

Pacific Medical Centers

Seattle, Washington, 98144, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

London Health Sciences Center

London, Ontario, N6A5A5, Canada

Location

Neuro-Epilepsy Clinic

Greenfield Park, Quebec, J4V2J2, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• Sperling MR, Harvey J, Grinnell T, Cheng H, Blum D; 045 Study Team. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America. Epilepsia. 2015 Apr;56(4):546-55. doi: 10.1111/epi.12934. Epub 2015 Feb 16.

  PMID: 25689448 BACKGROUND

MeSH Terms

Conditions

Seizures; Epilepsy

Interventions

eslicarbazepine acetate

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Limitations and Caveats

The comparison of active treatment to control which was used in this trial is based on a pooled analysis of comparator groups from 8 earlier trials of similar design. Limitations related to use of historical control groups are applicable.

Results Point of Contact

• Title: Eslicarbazepine acetate Medical Director
• Organization: Sunovion Phamaceuticals Inc.

clinicaltrialsdisclosure@sunovion.com

866-503-7813

Study Officials

• CNS Medical Director

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: March 18, 2009
• First Posted: March 20, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: March 11, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-02

Locations

CA (3); US (103)