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

• Proportion (%) of subjects that are seizure-free during the 10-week double-blind monotherapy treatment period. [ Time Frame: Weeks 9 through 18 ] [ Designated as safety issue: No ]
• Proportion (%) of subjects seizure-free during the last 4 weeks on eslicarbazepine acetate monotherapy. [ Time Frame: Weeks 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: Weeks 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 ]

• Proportion (%) of subjects that are seizure-free during the 10-week double-blind monotherapy treatment period. [ Time Frame: Weeks 9 through 18 ] [ Designated as safety issue: No ]
• Proportion (%) of subjects seizure-free during the last 4 weeks on eslicarbazepine acetate monotherapy. [ Time Frame: Weeks 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: Weeks 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 ]

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.

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.

• Drug: Eslicarbazepine acetate
  1600 mg QD
• Drug: Eslicarbazepine acetate
  1200 mg QD

• Experimental: Eslicarbazepine 1600 mg QD

  Subjects randomized to 1600 mg QD of eslicarbazepine acetate will titrate from 600 mg QD (Day 0) to 1200 mg QD (Week 1) to 1600 mg QD (Weeks 2-18)

  Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.

  Intervention: Drug: Eslicarbazepine acetate
• Experimental: Eslicarbazepine 1200 mg QD

  Subjects randomized to 1200 mg QD eslicarbazepine acetate will titrate from 400 mg QD (Day 0) to 800 mg QD (week 1) to 1200 mg QD (weeks 2-18)

  Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.

  Intervention: Drug: Eslicarbazepine acetate

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.