Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy

Partial Epilepsy Clinical Trial

Official title:

Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00957047
• Other study ID #: BIA-2093-302
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2009
• Last updated: June 23, 2014
• Start date: July 2004
• Est. completion date: January 2008

Study information

• Verified date: June 2014
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: National Pharmacy and Medicines Institute
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the efficacy of eslicarbazepine acetate once-daily at doses of 400 mg, 800 mg and 1200 mg compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period. Patients who complete Part I may enter a 1-year open-label extension.

Description:

Part I was a 22-week parallel-group, randomized, placebo-controlled period (8 weeks baseline, 2 weeks double-blind titration, and 12 weeks maintenance). After completing the baseline period, patients were randomized in a 1:1:1:1 ratio to 1 of the 3 ESL dose levels or to placebo.

Part II was a 1-year open-label extension for patients who had completed Part I. The starting dose was 800 mg once daily and could be titrated up or down at 400-mg intervals between 400 and 1200 mg.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 395
• Est. completion date: January 2008
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• written informed consent signed by patient

• aged 18 years or more

• documented diagnosis of simple or complex partial seizures with or without secondary generalisation since at least 12 months prior to screening

• at least 4 partial seizures in each 4 week period during the last 8 weeks prior to screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and felbamate), in a stable dose regimen during at least 2 months prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified)

• excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and laboratory tests

• post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential, patient must present a serum beta-hCG test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (oral contraception should be combined with a barrier method

Exclusion Criteria:

• only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) that are not video-EEG documented

• primarily generalised epilepsy

• known rapid progressive neurological disorder; history of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening

• seizures of psychogenic origin within the last 2 years

• history of schizophrenia or suicide attempt

• currently on or with exposure to felbamate or oxcarbazepine more within one month of screening

• using benzodiazepines on more than on an occasional basis (except when used chronically as AED)

• previous use of ESL or participation in a clinical study with ESL

• known hypersensitivity to carbamazepine, oxcarbazepine or chemically related substances

• history of abuse of alcohol, drugs or medications within the last 2 years

• uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder

• second or third-degree atrioventricular blockade not corrected with a pacemaker

• relevant clinical laboratory abnormalities

Study Design

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

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Partial Epilepsy

Intervention

Drug:
• eslicarbazepine acetate
oral tablets
• placebo
once daily placebo comparator
• ESL - Part II
Eslicarbazepine acetate was supplied as scored 800-mg tablets for daily oral administration.

Locations

Country	Name	City	State
Portugal	Bial - Portela & Cª, S.A.	S. Mamede do Coronado

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PART I - Seizure Frequency	The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the ITT population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.	12-week maintenance period	No
Primary	PART II - Nº of Treatment-Emergent Adverse Events (TEAE)	Safety assessments were based primarily on AEs (Number of patients who experienced at least one AEs), and on whether these were related to the study medication, were serious, led to permanent discontinuation of study participation, or led to death.	1 year	Yes