Partial Epilepsy in Children and Adolescents
Conditions
Keywords
Epilepsy, Partial, Refractory, Children, Adolescents, Adjunctive, Randomised, Double-blind, Placebo-controlled, Parallel-group
Brief summary
The purpose of this study is to examine the efficacy and safety of Eslicarbazepine acetate (BIA 2-093) when given with other anti-epileptic drugs to treat children with partial seizures whose condition has not been controlled by other drug treatments.
Detailed description
Partial epilepsy, the commonest form of epilepsy, is a difficult condition to treat with many patients continuing to have symptoms despite trying several medications. Lack of efficacy and adverse effects are commonly associated with current anti-epileptic drugs. This study will examine the efficacy in addition to safety and tolerability of a new anti-epileptic drug, Eslicarbazepine acetate (BIA 2-093), as an adjunctive therapy for refractory partial seizures in children. The primary analysis variables are: * The responder rate (the proportion of patients with at least a 50% reduction in standardised seizure frequency) * The relative reduction in standardised seizure frequency
Interventions
Part I - 8-week observational baseline period followed by a 6-week double-blind titration period, a 12-week double-blind maintenance period, a double-blind tapering-off period, and a 4-week observational period. The recommended target dose of double-blind study treatment will be 20mg/kg/day. Part II: At the end of part I, there is an option to enter a long-term open-label extension period to receive Eslicarbazepine acetate for 1 year.
Part I: 8-week observational baseline period followed by a 6-week double-blind titration period, a 12-week double-blind maintenance period, a double-blind tapering-off period, and a 4-week observational period. Part II: At the end of part I, there is an option to enter a long-term open-label extension period to receive Eslicarbazepine acetate for 1 year.
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* girls of child-bearing potential have to follow reliable and medically acceptable contraceptive method throughout the study * diagnosis of epilepsy for at least 6 months prior to enrolment * at least 4 partial-onset seizures in the last month prior to enrolment despite stable therapy with adequate dosage of 1 or 2 AEDs * at least 4 partial-onset seizures during each 4-week interval of the 8-week baseline period * previous treatment with three or more AEDs, in their maximum tolerated doses, for at least one month, without seizure control * current treatment with 1 or 2 AEDs (any except oxcarbazepine); if present, vagus nerve stimulation is considered an AED * stable dose regimen of AEDs during the 8-week baseline period * cooperation and willingness to complete all aspects of the study, including hospitalisation if required * written informed consent to participate in the study in accordance with local legislation
Exclusion criteria
* primarily generalised seizures * baseline seizure frequency substantially different from usual seizure frequency * known progressive neurological disorders * history of status epilepticus within the 3 months prior to enrolment * seizures of non-epileptic origin * Lennon-Gastaut * West syndrome * Major psychiatric disorders * Previous treatment any study with Eslicarbazepine acetate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Seizure Frequency | Baseline up to Visit 7 | Relative reduction in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period. |
| Responder Rate | baseline up to Visit 7 | Responder rate defined as the number of patients with at least a 50% decrease in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period. |
Countries
Austria, Bosnia and Herzegovina, Croatia, Czechia, France, Germany, Hungary, Italy, Malaysia, Moldova, Philippines, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Spain, Taiwan, Ukraine, United Kingdom
Participant flow
Recruitment details
73 clinical centres in 20 countries Date first patient enrolled: 07 Dec 2007. Date last patient completed the double-blind treatment period (Part I): 20 Aug 2012.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching placebo | 129 |
| Esl (BIA 2-093) Eslicarbazepine acetate (Esl) (BIA 2-093) The study treatment was ESL or matching placebo. These treatments were provided as an oral suspension (50 mg/mL) and as white oblong tablets (200 mg). | 134 |
| Total | 263 |
Baseline characteristics
| Characteristic | Total | Esl (BIA 2-093) | Placebo |
|---|---|---|---|
| Age, Customized 12-18 years | 97 participants | 52 participants | 45 participants |
| Age, Customized 2-6 years | 62 participants | 31 participants | 31 participants |
| Age, Customized 7-11 years | 104 participants | 51 participants | 53 participants |
| Sex: Female, Male Female | 137 Participants | 70 Participants | 67 Participants |
| Sex: Female, Male Male | 126 Participants | 64 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 129 | 112 / 134 |
| serious Total, serious adverse events | 9 / 129 | 15 / 134 |
Outcome results
Primary
Change From Baseline in Seizure Frequency
Relative reduction in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period.
Time frame: Baseline up to Visit 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Seizure Frequency | 62.0 seizures/month | Standard Deviation 186.19 |
| Esl (BIA 2-093) | Change From Baseline in Seizure Frequency | 36.6 seizures/month | Standard Deviation 72.47 |
p-value: 0.249ANCOVA
Primary
Responder Rate
Responder rate defined as the number of patients with at least a 50% decrease in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period.
Time frame: baseline up to Visit 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Responder Rate | 40 participants |
| Esl (BIA 2-093) | Responder Rate | 41 participants |
p-value: 0.9017Cochran-Mantel-Haenszel