Clinical trial NCT00866775: Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs
Official title: Double-Blind, Randomized, Historical Control Study of the Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy With Simple or Complex Partial Onset Seizures
Keywords: Seizure
Epilepsy
Anticonvulsant
Historical Control
Monotherapy
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2009-03-20
Enrollment: 193
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is an 18-week, double-blind, randomized, historical control, multicenter study with gradual conversion to monotherapy in subjects with partial onset seizures who are not well controlled by current AEDs. The 18 week double-blind treatment period consists of a 2-week period for titration of study drug, 6-week period for taper or conversion off AEDs, and a 10-week monotherapy period. Subjects not entering an optional open-label extension study will enter a 1-week period to taper off study drug followed by an end of study visit (week 19). This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Psychiatric exclusion criteria: subjects with history of suicide attempt in last 2 years; major depressive episode within last 6 months; abuse of alcohol or substance abuse in last 2 years; significant psychiatric disorder or recurrent episodes of severe depression within 2 years prior to screening.
* Medical exclusion criteria: known renal insufficiency or subject with estimated creatinine clearance \[CrCL\] \<60 mL/min based on serum creatinine using the Cockcroft-Gault formula.
* Clinical and laboratory exclusion criteria: Subjects of Asian ancestry who tests positive for the presence of the HLA-B\*1502 allele.
* 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.

Primary outcomes:
measure: Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
timeFrame: Week 3 to Week 18
Secondary outcomes:
measure: Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
timeFrame: Weeks 9 through 18
measure: Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
timeFrame: Weeks 15 through 18
measure: Completion Rate
timeFrame: Week 1 to Week 18
measure: Completion Rate During the 10 Weeks of Monotherapy
timeFrame: Weeks 8 through 18
measure: Time on Eslicarbazepine Acetate Monotherapy.
timeFrame: Week 8 to Week 18
measure: Change in Seizure Frequency From Baseline.
timeFrame: Week 0 to Week 18, Double-blind: weeks 1to 18; baseline:weeks-8 to -1; Titration: weeks 1 to 2; AED taper/conversion:weeks 3 to 8; monotherapy: weeks 9 to 18
measure: Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
timeFrame: Week 0 to Week 18, Double blind: weeks to 8; baseline:weeks -8 to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy: weeks 9 to 18
measure: Percentage of Subjects Reaching Each of the Exit Events.
timeFrame: Week 1 to Week 18
measure: Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
timeFrame: Week 0 to Week 18, baseline: day 0: End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
measure: Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
timeFrame: Week 0 to Week 18; Baseline: day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
measure: Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.
timeFrame: Week 0 to Week 18, Baseline: Day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
measure: Percentage of Subjects With Increase of Body Weight >= 7%
timeFrame: 18 Week Double-blind treatment period
measure: Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
timeFrame: 18 Week Double-blind treatment period
measure: Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
timeFrame: 18 Week Double-blind treatment period
measure: Standardized Seizure Frequency (SSF) by Period
timeFrame: Week 1 to Week 18, Double-blind: weeks 1 to 18; Baseline: weeks -8 to -1; Titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; Monotherapy: weeks 9 to 18
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Norwood Neurology
state: Alabama
city: Birmingham
country: United States
facility: Greystone Neurology Center
state: Alabama
city: Mobile
country: United States
facility: USA Neurology
state: Alabama
city: Northport
country: United States
facility: Neurology Clinic, P.C.
state: Alabama
city: Phoenix
country: United States
facility: Clinical Research Consortium
state: Arizona
city: Phoenix
country: United States
facility: Clinical Research Consortium - Arizona
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience Inc.
state: Arizona
city: Sun City
country: United States
facility: Arizona Neurological Institute
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Little Rock
country: United States
facility: K & S Professional Research Services
state: Arkansas
city: Berkley
country: United States
facility: Sutter East Bay Medical Foundation
state: California
city: Escondido
country: United States
facility: Synergy Escondido
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Loma Linda
country: United States
facility: Faculty of Physicians & Surgeons of Loma Linda University
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Los Gatos
country: United States
facility: American Institute of Research
state: California
city: Northridge
country: United States
facility: Northridge Neurological Center
state: California
city: Pasadena
country: United States
facility: Yafa Minazad, DO
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Aurora
country: United States
facility: Anschutz Outpatient Pavilion
state: Colorado
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Danbury
country: United States
facility: Associated Neurologists, PC
state: Connecticut
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Coral Gables
country: United States
facility: Miami Clinical Research
state: Florida
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LLC
state: Florida
city: Hollywood
country: United States
facility: Infiniti Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, PA
state: Florida
city: Melbourne
country: United States
facility: MIMA Century Research Associates
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic
state: Florida
city: Miami
country: United States
facility: Neurosciences Consultants, LLC
state: Florida
city: Orlando
country: United States
facility: Neurological Services Orlando
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurolog, PA
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates of Ormond Beach
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic
state: Florida
city: Tampa
country: United States
facility: Pediatric Epilepsy & Neurology Specialists, PA
state: Florida
city: Tampa
country: United States
facility: Florida Comprehensive Epilepsy and Seizure Disorder Center
state: Florida
city: Vero Beach
country: United States
facility: Vero Neurology
state: Florida
city: Wellington
country: United States
facility: Palm Beach Clinical Research Network LLC
state: Florida
city: Atlanta
country: United States
facility: Peachtree Neurological Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Department of Neurology
state: Georgia
city: Atlanta
country: United States
facility: PANDA Neurology and Atlanta Headache Specialists
state: Georgia
city: Rome
country: United States
facility: Harbin Clinic
state: Georgia
city: Suwanee
country: United States
facility: GA Neurology and Sleep Medicine Associates
state: Georgia
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology, PLLC.
state: Idaho
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: UCMC
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research LLC
state: Kentucky
city: Hammond
country: United States
facility: North Oaks Neurology
state: Louisiana
city: Scarborough
country: United States
facility: MMP Neurology
state: Maine
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Epilepsy Service - WACC
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Chesterfield
country: United States
facility: The Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: St. Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Camden
country: United States
facility: Cooper University Health System
state: New Jersey
city: Cherry Hill
country: United States
facility: Cooper University Health System
state: New Jersey
city: Edison
country: United States
facility: NJ Neuroscience Center
state: New Jersey
city: Livingston
country: United States
facility: Institute of Neurology and Neurosurgery at St. Bamabas, Suite 101
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Cedarhurst
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Clinilabs Inc.
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: The Neurology Institute
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory, LLC
state: North Carolina
city: Winstom-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Bellevue
country: United States
facility: Northern Ohio Neurosciences
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: 5929 N. May Ave.
state: Oklahoma
city: Medford
country: United States
facility: Providence Medical Group
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburg
country: United States
facility: Children's Hospital of Pittsburg of UPMC
state: Pennsylvania
city: Cranston
country: United States
facility: Gus Stratton / Neurology
state: Rhode Island
city: Germantown
country: United States
facility: Mid-South Physcians Group
state: Tennessee
city: Nashville
country: United States
facility: Access Clinical Trials
state: Tennessee
city: Nashville
country: United States
facility: VU Department of Neurology
state: Tennessee
city: Arlington
country: United States
facility: Neurology Associates of Arlington, PA
state: Texas
city: Dallas
country: United States
facility: Texas Neurology, PA
state: Texas
city: Dallas
country: United States
facility: Neurological Clinic of Texas P.A.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: UT Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Todd Swick, MD, PA
state: Texas
city: Mansfield
country: United States
facility: Neurology Associates of Arlington, PA
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Bellevue
country: United States
facility: Neurological Associates of Washington/Clinical Trials of America Inc.
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
city: Seattle
country: United States
facility: Pacific Medical Centers
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Greenfield Park
country: Canada
facility: Neuro-Epilepsy Clinic
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: CNS Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.