Clinical trial NCT01091662: Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w/Partial Epilepsy Not Well Controlled by Current Antiepileptic
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
Keywords: Seizures
Epilepsy
Anticonvulsant
Monotherapy
Historical control
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2010-03-24
Enrollment: 172
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 titration period, 6-week taper or conversion period, and a 10-week monotherapy period. 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)

  * Medical history of seizures;
  * Absence of confounding factors (pseudoseizures, syncope);
  * 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 structural abnormality (eg, tumor or malformation)
* ≥ 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:

  * Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal);
  * 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
* Medical exclusion criteria: known renal insufficiency (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

Primary outcomes:
measure: Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
timeFrame: From beginning of Week 3 to end of Week 18
Secondary outcomes:
measure: Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
timeFrame: Week 9 through 18
measure: Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
timeFrame: Week 15 through 18
measure: Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment).
timeFrame: 18 weeks
measure: Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete).
timeFrame: Week 8 through 18
measure: Time on Eslicarbazepine Acetate Monotherapy.
timeFrame: Week 8 to Week 18
measure: Change in Seizure Frequency From Baseline.
timeFrame: 18 weeks, Double-blind:weeks 1-18; Baseline: weeks -8to -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 1-18; baseline: weeks -8 to -1; Titration: weeks 1-2; AED taper/conversion; weeks 3-8; monotherapy weeks 9-18
measure: Proportion (%) of Subjects Reaching Each Exit Criteria
timeFrame: Week 1 to Week 18, (beginning of week 1 to end of 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 in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline .
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 of MADRS From Baseline 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: Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline
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: Week 0 to Week 18
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: Double-blind: week 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: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Conway
country: United States
facility: Arkansas Neurology
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Bakersfield
country: United States
facility: Kern County Neurological Medical Group, INC.
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Medical Center
state: California
city: Ventura
country: United States
facility: Neurosearch II Inc.
state: California
city: Englewood
country: United States
facility: Specialty Nuerology, PC
state: Colorado
city: Hialeah
country: United States
facility: Palm Springs Research Institute, Inc
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Miami
country: United States
facility: Pharma Care Research LLC
state: Florida
city: Panama City
country: United States
facility: Bay Neurological Institute
state: Florida
city: Venice
country: United States
facility: Loveland Scientific Resources Inc.
state: Florida
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology PC
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Department of Neurology
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Science Center - Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: The Sandra and Malcom Berman Brain & Spine Institute
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Detroit Medical Center
state: Michigan
city: Golden Valley
country: United States
facility: Minneappolis Clinic of Neurology
state: Minnesota
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Newark
country: United States
facility: UMDNJ DOC 8th Floor 8100
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes, LLC
state: New Jersey
city: Toms River
country: United States
facility: Shore Neurology, PA
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Orchard Park
country: United States
facility: Dent Neurologic Institute
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Department of Neurology
state: New York
city: Greenville
country: United States
facility: East Carolina Neurology
state: North Carolina
city: Canton
country: United States
facility: Ohio Clinical Research Partners, LLC
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Research LLC
state: Oklahoma
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Austin
country: United States
facility: Community Clinical Research Inc.
state: Texas
city: Brownwood
country: United States
facility: Brownwood Regional Medical Center
state: Texas
city: Dallas
country: United States
facility: MD
state: Texas
city: DeSoto
country: United States
facility: Vital Clinical Research
state: Texas
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Regional Epilepsy Center
state: Wisconsin
city: Blagoevgrad
country: Bulgaria
facility: Multirprofile Hospital for Active Treatment "Pulse," AD, town of Blagoevgrad
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski," EAD, town of Pleven
city: Sofia
country: Bulgaria
facility: Second Multiprofile Hospital for Active Treatment - Sofia, AD, city of Sofia Neurology Department
city: Varna
country: Bulgaria
facility: Diagnostic and Consultative Center "Equita" EOOD, town of Varna
city: Smetanova
country: Czech Republic
facility: Policlinic Chocen, private neurology
state: Chocen
city: Praha
country: Czech Republic
state: Pocernicka
city: Kolejni
country: Czech Republic
facility: Neurologicka ordinance
state: Praha
city: Rychnov nad Kneznou
country: Czech Republic
facility: CTC Rycnov nad Kneznou
state: Praugue
city: Ostrava
country: Czech Republic
facility: Cerebrovaskularni poradna s.r.o.
state: Tiebovice
city: Koterova
country: Czech Republic
facility: Poradna pro epilepsie
state: Zin
city: Palmoticeva
country: Serbia
facility: Institute of Mental Health, Department of epilepsy and clinical neurophysiology
state: Belgrade
city: Belgrade
country: Serbia
facility: Clinic of Neurology, Clinical Center of Serbia
city: Dnipropetrovsk
country: Ukraine
facility: Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after l.l. Mechnikov" Regional Center of psychosomatic disorders, Psychoneurology department for patients with psychosomatic disorders and borderline condtions
city: Donetsk
country: Ukraine
facility: Communal Medical and Preventive Treatment Institution "Regional Clincal Psychiatric Hospital" Donetsk National Medical University
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of neurology, psychiatry and narcology of AMS of Ukraine" Department of cerebrovascular patology
city: Kharkov
country: Ukraine
facility: State Treatment and Prevention Institution
city: Kharkov
country: Ukraine
facility: State Institution "Institute of the Health Care of Children & Adolescents of Academy of Medical Sciences of Ukraine" Dept of Psychiatry
city: Kiev
country: Ukraine
facility: State Institution Railway Clinical Hospital #1 of Kiev Railway Station of DTGO South Western Railroad Psycho-neurological Department
city: Lviv
country: Ukraine
facility: Communal Institution "Lviv Regional Clinical Psychiatric Hospital" Department #20, Lviv National Medical University, named after Danylo
city: Odessa
country: Ukraine
facility: Communal Institution "Odessa Regional Clinical Psych Hospital #1" Department of Day Care
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Psychiatric Hospital named O.F. Maltsev
city: Simferopol
country: Ukraine
facility: Crimean Republic Institution "Clinical Psychiatric Hospital #1"
city: Vinnytsia
country: Ukraine
facility: Communal Institution "Vinnytsia Regional Psycho-Neurological Hospital named after O.I. Yuschenko, Vinnytsia National Medical University named after M.I. Pirogov, Dispensary department, Department of Psychiatry and Addictology
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: CNS Medical Dirctor
role: STUDY_DIRECTOR
References:
citation: Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D; study 046 team. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5.