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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01091662
• Date of registration: 17/03/2010
• Prospective Registration: Yes
• Primary sponsor: Sunovion
• Public title: Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w/Partial Epilepsy Not Well Controlled by Current Antiepileptic
• Scientific 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
• Date of first enrolment: June 2010
• Target sample size: 172
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01091662
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Bulgaria, Czech Republic, Serbia, Ukraine, United States

Contacts

• Name: CNS Medical Dirctor
• Affiliation: Sunovion

Key inclusion & exclusion 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



Age minimum: 16 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Epilepsy

Intervention(s)

Drug: Eslicarbazepine acetate 1600 mg

Drug: Eslicarbazepine acetate 1200 mg

Primary Outcome(s)

Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method [Time Frame: From beginning of Week 3 to end of Week 18]

Secondary Outcome(s)

Change in Seizure Frequency From Baseline. [Time Frame: 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]

Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete). [Time Frame: Week 8 through 18]

Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. [Time Frame: Week 9 through 18]

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]

Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). [Time Frame: 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]

Responder Rate (Proportion [%] of Subjects With a =50% Reduction of Seizure Frequency From Baseline). [Time Frame: 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]

Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment). [Time Frame: 18 weeks]

Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of =14 at Randomization. [Time Frame: 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]

Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . [Time Frame: 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]

Time on Eslicarbazepine Acetate Monotherapy. [Time Frame: Week 8 to Week 18]

Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. [Time Frame: Week 15 through 18]

Proportion (%) of Subjects Reaching Each Exit Criteria [Time Frame: Week 1 to Week 18, (beginning of week 1 to end of week 18)]

Standardized Seizure Frequency (SSF) by Period [Time Frame: 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]

Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline [Time Frame: 18 Week Double-blind treatment period]

Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). [Time Frame: 18 Week Double-blind treatment period]

Secondary ID(s)

093-046

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/12/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01091662