Epilepsy
Conditions
Keywords
Epilepsy, BIA 2-093
Brief summary
The purpose of this study is to determine the efficacy of BIA 2 093 in the treatment of epileptic patients with refractory simple or complex partial seizures with or without secondary generalization.
Detailed description
This clinical trial was performed as a multicentre, add-on, double-blind, randomised, placebo-controlled, phase II study. During the double-blind treatment phase (12 weeks) patients were assigned to three treatment groups receiving BIA 2 093 once daily (ODG - once-daily group), BIA 2 093 twice daily (TDG - twice-daily group) or placebo (PLG - placebo group), respectively. Daily doses of BIA 2 093 were increased at four-weekly periods (400 mg, 800 mg and 1200 mg). On completion of the 12-week double-blind treatment period, a 1-week tapering period was scheduled.
Interventions
DRUGBIA 2-093
BIA 2-093 (tablets) administered at increasing daily doses of 400 mg, 800 mg and 1200 mg once-daily or twice-daily, oral route
DRUGPlacebo
Placebo tablets administered orally
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients aged 18-65 years * Patients with simple or complex partial seizures with or without secondary generalization since at least one year prior to randomisation visit * At least 4 seizures per month within the last 2 months prior to randomisation * Stable dose regimen of a maximum of two of the following AEDs: phenytoin, valproate, primidone, phenobarbital, lamotrigine, gabapentin, topiramate, clonazepam, during 2 months prior to randomisation * Electroencephalogram (EEG) findings not contradicting the epilepsy diagnosis (e.g., primarily generalized epilepsy) * Written informed consent.
Exclusion criteria
* Patient with nervus vagus stimulation * Patient with primarily generalized seizures * Known progressive neurological disturbance * A history of status epilepticus within the past 3 months * Seizure of non-epileptic origin * Restricted legal competence and incapability to follow trial instructions * Major psychiatric disorders * Concurrent drug therapy with monoamine oxidase inhibitors or calcium channel blockers * Need of excluded concomitant medication (see section 9.4.6.2) * Use of oxcarbazepine or carbamazepine during the last 6 months before the randomisation visit * Known hypersensitivity to oxcarbazepine or carbamazepine, or its metabolites * Abuse of alcohol, drugs or medications * History of relevant cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, hematologic or oncology disorders * Second- or third-degree atrioventricular block not corrected with a pacemaker * Relevant laboratory abnormalities (e.g., Na+\< 130 mmol/L, alanine (ALT) or aspartate (AST) transaminase \>2.0 times the upper limit of normal, white blood cell (WBC) count \<3000 cells/mm3) * Pregnancy, nursing or inadequate contraception in women of childbearing age (oral contraception should be combined with a barrier method) * Participation in other clinical trials within the last 2 months * History of non-compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period | baseline, week 12 |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ODG - Once-daily Group BIA 2-093 once-daily; Daily doses of BIA 2-093 were increased at four-weekly periods (400 mg, 800 mg and 1200 mg).
BIA 2-093: BIA 2-093 (tablets) administered at increasing daily doses of 400 mg, 800 mg and 1200 mg once-daily or twice-daily, oral route | 50 |
| TDG - Twice-daily Group BIA 2-093 twice-daily; Daily doses of BIA 2-093 were increased at four-weekly periods (400 mg, 800 mg and 1200 mg).
BIA 2-093: BIA 2-093 (tablets) administered at increasing daily doses of 400 mg, 800 mg and 1200 mg once-daily or twice-daily, oral route | 47 |
| PLG - Placebo Group placebo
Placebo: Placebo tablets administered orally | 47 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 4 |
| Overall Study | Exacerbation of seizures | 0 | 2 | 1 |
| Overall Study | Exclusion criteria | 2 | 2 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 2 |
Baseline characteristics
| Characteristic | ODG - Once-daily Group | TDG - Twice-daily Group | PLG - Placebo Group | Total |
|---|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 11.4 | 39.8 years STANDARD_DEVIATION 11.9 | 40.4 years STANDARD_DEVIATION 10.8 | 39.8 years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 29 Participants | 31 Participants | 27 Participants | 87 Participants |
| Sex: Female, Male Male | 21 Participants | 16 Participants | 20 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 50 | 19 / 46 | 21 / 47 |
| serious Total, serious adverse events | 2 / 50 | 0 / 46 | 1 / 47 |
Outcome results
Primary
The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period
Time frame: baseline, week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ODG - Once Daily Group | The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period | 54 percentage of responders |
| TDG - Twice Daily Group | The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period | 41 percentage of responders |
| PLG - Placebo Group | The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period | 28 percentage of responders |