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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT01091662
First received: March 17, 2010
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Epilepsy
Drug: Eslicarbazepine acetate 1600 mg
Drug: Eslicarbazepine acetate 1200 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Proportion (%) of subjects meeting at least one of the five exit criteria over a 16-week study period [ Time Frame: Week 18 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion (%) of subjects that are seizure-free during the 10-week double-blind monotherapy treatment period. [ Time Frame: Week 9 through 18 ] [ Designated as safety issue: No ]
  • Proportion (%) of subjects seizure-free during the last 4 weeks on eslicarbazepine acetate monotherapy. [ Time Frame: Week 15 through 18 ] [ Designated as safety issue: No ]
  • Completion rate (% of subjects completing the 18 weeks of double-blind treatment). [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Completion rate during the 10 weeks of monotherapy (% of subjects entering the monotherapy period who complete). [ Time Frame: Week 8 through 18 ] [ Designated as safety issue: No ]
  • Time on eslicarbazepine acetate monotherapy. [ Time Frame: Week 8 to Week 18 ] [ Designated as safety issue: No ]
  • Change in seizure frequency from baseline. [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Responder rate (proportion [%] of subjects with a ≥50% reduction of seizure frequency from baseline). [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Proportion (%) of subjects reaching each of the exit events. [ Time Frame: Week 2 to Week 18 ] [ Designated as safety issue: No ]
  • Change in total score from baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Change in total score from baseline in Montgomery-Asberg Depression Rating Scale (MADRS). [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Change in total score from baseline in MADRS in those subjects with a MADRS score of ≥14 at randomization. [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Proportion (%) of subjects with increase of body weight >= 7% [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Proportion (%) of subjects with normal baseline sodium reaching blood sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]
  • Proportion (%) of events in each classification of the Columbia Suicide Severity Rating Scale (C SSRS). [ Time Frame: Week 0 to Week 18 ] [ Designated as safety issue: No ]

Enrollment: 174
Study Start Date: June 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: eslicarbazepine acetate 1600 mg
Subjects randomized to 1600 mg QD of eslicarbazepine acetate will titrate from 600 mg QD(Day 0) to 1200 mg once a day(Week 2) to 1600 mg QD (Weeks 3-18) and may taper down from 1600 mg to 800 mg QD 3 days after the Week 18 visit.
Drug: Eslicarbazepine acetate 1600 mg
1600 mg once per day
Experimental: eslicarbazepine acetate 1200 mg

Subjects randomized to 1200 mg QD eslicarbazepine acetate will titrate from 400 mg QD (Day0) to 800 mg QDweek2) to 1200 mg QD(weeks 3-18) and may taper down from 1200 mg to 600 mg QD 3 days after the Week 18 visit.

Subjects may continue in an open-label extension study with a starting dose of 1200 mg QD, or taper off their previous antiepileptic drugs during weeks 2-8.

Drug: Eslicarbazepine acetate 1200 mg
1200 once per day

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

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01091662

  Hide Study Locations
Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Arkansas
Arkansas Neurology
Conway, Arkansas, United States, 72034
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Kern County Neurological Medical Group, INC.
Bakersfield, California, United States, 93301
Neuro-Pain Medical Center
Fresno, California, United States, 93710
West Los Angeles VA Medical Center
Los Angeles, California, United States, 90073
Neurosearch II Inc.
Ventura, California, United States, 93003
United States, Colorado
Specialty Nuerology, PC
Englewood, Colorado, United States, 80113
United States, Florida
Palm Springs Research Institute, Inc
Hialeah, Florida, United States, 33012
Pharma Care Research LLC
Miami, Florida, United States, 33165
Miami Children's Hospital
Miami, Florida, United States, 33155
Bay Neurological Institute
Panama City, Florida, United States, 32405
Loveland Scientific Resources Inc.
Venice, Florida, United States, 34292
United States, Indiana
Josephson Wallack Munshower Neurology PC
Indianapolis, Indiana, United States, 46237
United States, Kentucky
University of Kentucky Department of Neurology
Lexington, Kentucky, United States, 40536
United States, Louisiana
Louisiana State University Health Science Center - Shreveport
Shreveport, Louisiana, United States, 71103
United States, Maryland
The Sandra and Malcom Berman Brain & Spine Institute
Baltimore, Maryland, United States, 21209
United States, Massachusetts
Lahey Clinic
Burlington, Massachusetts, United States, 01805
United States, Michigan
Wayne State University/Detroit Medical Center
Detroit, Michigan, United States, 48201
United States, Minnesota
Minneappolis Clinic of Neurology
Golden Valley, Minnesota, United States, 55422
United States, New Jersey
Northeast Regional Epilepsy Group
Hackensack, New Jersey, United States, 07601
UMDNJ DOC 8th Floor 8100
Newark, New Jersey, United States, 07103
Global Medical Institutes, LLC
Princeton, New Jersey, United States, 08540
Shore Neurology, PA
Toms River, New Jersey, United States, 08755
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Dent Neurologic Institute
Orchard Park, New York, United States, 14127
SUNY Upstate Medical University Department of Neurology
Syracuse, New York, United States, 13210
United States, North Carolina
East Carolina Neurology
Greenville, North Carolina, United States, 27834
United States, Ohio
Ohio Clinical Research Partners, LLC
Canton, Ohio, United States, 44718
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oklahoma
Tulsa Clinical Research LLC
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
Temple University School of Medicine
Philadelphia, Pennsylvania, United States, 19140
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
United States, Texas
Community Clinical Research Inc.
Austin, Texas, United States, 78754
Brownwood Regional Medical Center
Brownwood, Texas, United States, 76801
MD
Dallas, Texas, United States, 75214
Vital Clinical Research
DeSoto, Texas, United States, 75115
United States, Wisconsin
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Regional Epilepsy Center
Milwaukee, Wisconsin, United States, 53215
Bulgaria
Multirprofile Hospital for Active Treatment "Pulse," AD, town of Blagoevgrad
Blagoevgrad, Bulgaria, 2700
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski," EAD, town of Pleven
Pleven, Bulgaria, 5800
Second Multiprofile Hospital for Active Treatment - Sofia, AD, city of Sofia Neurology Department
Sofia, Bulgaria, 1202
Diagnostic and Consultative Center "Equita" EOOD, town of Varna
Varna, Bulgaria, 9000
Czech Republic
Policlinic Chocen, private neurology
Smetanova, Chocen, Czech Republic, 56501
Praha, Pocernicka, Czech Republic, 1427 16
Neurologicka ordinance
Kolejni, Praha, Czech Republic, 160 00
CTC Rycnov nad Kneznou
Rychnov nad Kneznou, Praugue, Czech Republic, 516 01
Cerebrovaskularni poradna s.r.o.
Ostrava, Tiebovice, Czech Republic, 72200
Poradna pro epilepsie
Koterova, Zin, Czech Republic, 760 01
Serbia
Institute of Mental Health, Department of epilepsy and clinical neurophysiology
Palmoticeva, Belgrade, Serbia, 11000
Clinic of Neurology, Clinical Center of Serbia
Belgrade, Serbia, 11000
Ukraine
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
Dnipropetrovsk, Ukraine, 49005
Communal Medical and Preventive Treatment Institution "Regional Clincal Psychiatric Hospital" Donetsk National Medical University
Donetsk, Ukraine, 83008
State Institution "Institute of neurology, psychiatry and narcology of AMS of Ukraine" Department of cerebrovascular patology
Kharkiv, Ukraine, 61068
State Treatment and Prevention Institution
Kharkov, Ukraine, 61018
State Institution "Institute of the Health Care of Children & Adolescents of Academy of Medical Sciences of Ukraine" Dept of Psychiatry
Kharkov, Ukraine, 61153
State Institution Railway Clinical Hospital #1 of Kiev Railway Station of DTGO South Western Railroad Psycho-neurological Department
Kiev, Ukraine, 01030
Communal Institution "Lviv Regional Clinical Psychiatric Hospital" Department #20, Lviv National Medical University, named after Danylo
Lviv, Ukraine, 79021
Communal Institution "Odessa Regional Clinical Psych Hospital #1" Department of Day Care
Odessa, Ukraine, 65006
Poltava Regional Clinical Psychiatric Hospital named O.F. Maltsev
Poltava, Ukraine, 36003
Crimean Republic Institution "Clinical Psychiatric Hospital #1"
Simferopol, Ukraine, 95006
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
Vinnytsia, Ukraine, 21005
Sponsors and Collaborators
Sunovion
  More Information

No publications provided

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT01091662     History of Changes
Other Study ID Numbers: 093-046
Study First Received: March 17, 2010
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sunovion:
Seizures
Epilepsy
Anticonvulsant
Monotherapy
Historical control

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014