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

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

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
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.


Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01091662

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Responsible Party: Sunovion 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:
Historical control

Additional relevant MeSH terms:
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Eslicarbazepine acetate
Cardiovascular Agents
Central Nervous System Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers processed this record on February 27, 2015