Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w/Partial Epilepsy Not Well Controlled by Current Antiepileptic

NCT01091662 | Completed Phase 3 Results

• 1 other identifier: 093-046
• Study Type: interventional
• Target: 172
• Locations: 5 countries
• Sites: 62

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

Keywords

Seizures; Epilepsy; Anticonvulsant; Monotherapy; Historical control

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 following five exit criteria over a 16-week study period (from start of AED taper/con. period (Wk 3) to end of double blind monotherapy period (Wk 18)).1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. 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 week 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 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week 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

  From beginning of Week 3 to end of Week 18

Secondary Outcomes (15)

• Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.

  Week 9 through 18

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

  Week 15 through 18

• Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment).

  18 weeks

• Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete).

  Week 8 through 18

• Time on Eslicarbazepine Acetate Monotherapy.

  Week 8 to Week 18

Study Arms (2)

eslicarbazepine acetate 1600 mg

EXPERIMENTAL

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

eslicarbazepine acetate 1200 mg

EXPERIMENTAL

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

Interventions

Eslicarbazepine acetate 1600 mg DRUG

1600 mg once per day

eslicarbazepine acetate 1600 mg

Eslicarbazepine acetate 1200 mg DRUG

1200 once per day

eslicarbazepine acetate 1200 mg

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)
• 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

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

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (62)

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Arkansas Neurology

Conway, Arkansas, 72034, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Kern County Neurological Medical Group, INC.

Bakersfield, California, 93301, United States

Location

Neuro-Pain Medical Center

Fresno, California, 93710, United States

Location

West Los Angeles VA Medical Center

Los Angeles, California, 90073, United States

Location

Neurosearch II Inc.

Ventura, California, 93003, United States

Location

Specialty Nuerology, PC

Englewood, Colorado, 80113, United States

Location

Palm Springs Research Institute, Inc

Hialeah, Florida, 33012, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Pharma Care Research LLC

Miami, Florida, 33165, United States

Location

Bay Neurological Institute

Panama City, Florida, 32405, United States

Location

Loveland Scientific Resources Inc.

Venice, Florida, 34292, United States

Location

Josephson Wallack Munshower Neurology PC

Indianapolis, Indiana, 46237, United States

Location

University of Kentucky Department of Neurology

Lexington, Kentucky, 40536, United States

Location

Louisiana State University Health Science Center - Shreveport

Shreveport, Louisiana, 71103, United States

Location

The Sandra and Malcom Berman Brain & Spine Institute

Baltimore, Maryland, 21209, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

Wayne State University/Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

Minneappolis Clinic of Neurology

Golden Valley, Minnesota, 55422, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

UMDNJ DOC 8th Floor 8100

Newark, New Jersey, 07103, United States

Location

Global Medical Institutes, LLC

Princeton, New Jersey, 08540, United States

Location

Shore Neurology, PA

Toms River, New Jersey, 08755, United States

Location

Dent Neurologic Institute

Orchard Park, New York, 14127, United States

Location

SUNY Upstate Medical University Department of Neurology

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

East Carolina Neurology

Greenville, North Carolina, 27834, United States

Location

Ohio Clinical Research Partners, LLC

Canton, Ohio, 44718, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Tulsa Clinical Research LLC

Tulsa, Oklahoma, 74104, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Community Clinical Research Inc.

Austin, Texas, 78754, United States

Location

Brownwood Regional Medical Center

Brownwood, Texas, 76801, United States

Location

MD

Dallas, Texas, 75214, United States

Location

Vital Clinical Research

DeSoto, Texas, 75115, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Regional Epilepsy Center

Milwaukee, Wisconsin, 53215, United States

Location

Multirprofile Hospital for Active Treatment "Pulse," AD, town of Blagoevgrad

Blagoevgrad, Bulgaria, 2700, Bulgaria

Location

Second Multiprofile Hospital for Active Treatment - Sofia, AD, city of Sofia Neurology Department

Sofia, Bulgaria, 1202, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski," EAD, town of Pleven

Pleven, Pleven, 5800, Bulgaria

Location

Diagnostic and Consultative Center "Equita" EOOD, town of Varna

Varna, Varna, 9000, Bulgaria

Location

Policlinic Chocen, private neurology

Smetanova, Chocen, 56501, Czechia

Location

Unknown Facility

Prague, Pocernicka, 1427 16, Czechia

Location

Neurologicka ordinance

Kolejni, Prague, 160 00, Czechia

Location

CTC Rycnov nad Kneznou

Rychnov nad Kněžnou, Praugue, 516 01, Czechia

Location

Cerebrovaskularni poradna s.r.o.

Ostrava, Tiebovice, 72200, Czechia

Location

Poradna pro epilepsie

Koterova, Zin, 760 01, Czechia

Location

Clinic of Neurology, Clinical Center of Serbia

Belgrade, Belgrade, 11000, Serbia

Location

Institute of Mental Health, Department of epilepsy and clinical neurophysiology

Palmoticeva, Belgrade, 11000, Serbia

Location

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, Dnipropetrovsk Oblast, 49005, Ukraine

Location

Communal Medical and Preventive Treatment Institution "Regional Clincal Psychiatric Hospital" Donetsk National Medical University

Donetsk, Donetsk Oblast, 83008, Ukraine

Location

State Institution "Institute of neurology, psychiatry and narcology of AMS of Ukraine" Department of cerebrovascular patology

Kharkiv, Kharkivs’ka Oblast’, 61068, Ukraine

Location

State Treatment and Prevention Institution

Kharkiv, Kharkov, 61018, Ukraine

Location

State Institution "Institute of the Health Care of Children & Adolescents of Academy of Medical Sciences of Ukraine" Dept of Psychiatry

Kharkiv, Kharkov, 61153, Ukraine

Location

State Institution Railway Clinical Hospital #1 of Kiev Railway Station of DTGO South Western Railroad Psycho-neurological Department

Kiev, Kyiv City, 01030, Ukraine

Location

Communal Institution "Lviv Regional Clinical Psychiatric Hospital" Department #20, Lviv National Medical University, named after Danylo

Lviv, Lviv Oblast, 79021, Ukraine

Location

Communal Institution "Odessa Regional Clinical Psych Hospital #1" Department of Day Care

Odesa, Odesa Oblast, 65006, Ukraine

Location

Poltava Regional Clinical Psychiatric Hospital named O.F. Maltsev

Poltava, Poltava Oblast, 36003, Ukraine

Location

Crimean Republic Institution "Clinical Psychiatric Hospital #1"

Simferopol, Simferopol, 95006, Ukraine

Location

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, Vinnytsia Oblast, 21005, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 25880756 BACKGROUND

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

eslicarbazepine acetate

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

clinicaltrialsdisclosure@sunovion.com

866-503-7813

Study Officials

• CNS Medical Dirctor

  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 17, 2010
• First Posted: March 24, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 24, 2016
• Results First Posted: December 21, 2015

Record last verified: 2016-09

Locations

SE (2); UA (11); CZ (6); US (39); BU (4)