| Study summary: |
|
The efficacy of Eslicarbazepine acetate (BIA 2-093)will be evaluated at doses of 800 mg and
1200 mg once daily over a 12-week maintenance period.
This is a 2-part study. Part I will follow a parallel-group, randomised, placebo-controlled
design and will consist of an 8-week baseline period, followed by a double-blind 2-week
titration period and a 12-week maintenance period. At the end of the 8-week baseline period,
patients will be randomly assigned to one of three treatment groups in a 1:1:1 ratio:
Placebo (Group 1; n=120), Eslicarbazepine acetate 800 mg QD (Group 2; n=120) and
Eslicarbazepine acetate 1200 mg QD (Group 3; n=120).
Patients who complete Part I may enter a 1-year open-label extension (Part II) with
Eslicarbazepine acetate, starting with a dose of 800 mg QD for one month. Thereafter,
investigators can titrate the dose upwards or downwards. |
| Criteria: |
|
Inclusion Criteria
At V1 (screening), patient must be/have:
1. Written informed consent signed by patient.
2. Aged 16 years or more (patients under 18 years of age require parental/legal
representative consent). In North America as well as in other participating
countries, when appropriate and/or required by state or local law, minor patients
must give written informed assent prior to participation in the study.
3. A documented diagnosis of epilepsy since at least 12 months prior to screening.
4. At least 4 partial-onset seizures (including subtypes of simple partial, complex
partial and partial seizures evolving to secondarily generalised) on the 4 weeks
prior to screening.
5. Currently treated with 1 or 2 AEDs (any except OXC), in a stable dose regimen during
at least 1 month prior to screening. Patients using vigabatrin should have been on
this medication for at least 1 year with no deficit in visual field identified (a
confirmatory test should be available within 1 month before study entry). The device
for VNS should be implanted at least 6 months before screening; parameters need to be
stable for at least 1 month prior to screening (VNS will not be counted as
concomitant AED).
6. Excepting epilepsy, patient is judged to be in general good health based on medical
history, physical examination findings, and clinical laboratory test results.
7. Post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or
tubal ligation. In case of women of childbearing potential (WOCBP), patient must
present a serum beta-human chorionic gonadotropin (B-hCG) test consistent with a non
gravid state and agree to remain abstinent or use reliable contraception (hormonal
contraception should be combined with a barrier method) beginning at screening and
continuing at least to the PSV.
At V2 (randomisation), patient must have:
8. At least 8 partial-onset seizures during baseline with at least 3 partial-onset
seizures in each 4-week section of the 8-week baseline period prior to randomisation
(documented in a diary) and no seizure-free interval exceeding 28 consecutive days.
9. In case of WOCBP, patient must present a urine B-hCG test consistent with a non
gravid state.
10. Diaries satisfactorily completed by the patient or his/her caregiver.
11. Satisfactorily complied with the study requirements during the baseline period
(including no changes in concomitant AED therapy should have occurred in the baseline
period).
Exclusion Criteria
At V1 (screening), patients must not be/have:
1. Only simple partial seizures with no motor symptomatology (classified as A2 4
according to the International Classification of Epileptic Seizures).
2. Primarily generalised seizures.
3. Known progressive neurological disorders (progressive brain disease; epilepsy
secondary to progressive cerebral lesion).
4. Occurrence of seizures too close to count accurately.
5. History of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30
minutes) within the 3 months prior to screening.
6. Seizures of non-epileptic origin.
7. Seizures of psychogenic origin within the last 2 years.
8. Major psychiatric disorders.
9. Documented diagnosis of schizophrenia with accompanying documented history of at
least 1 acute psychosis episode within the last 2 years) or history of suicide
attempt.
10. Currently treated with OXC.
11. Using benzodiazepines on more than an occasional basis (defined as more than 2 times
per week), except when used chronically as AED.
12. Known exposure to Eslicarbazepine acetate from previous study.
o Previous use of Eslicarbazepine acetate or participation in a clinical study with
Eslicarbazepine acetate (patients not exposed to Eslicarbazepine acetate [e.g.,
screen failed] are allowed).
13. Known hypersensitivity to carboxamide derivatives.
14. History of abuse of alcohol, drugs or medications within the last 2 years.
15. Uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic,
haematological or oncology disorder.
16. Second or third-degree atrioventricular blockade not corrected with a pacemaker.
17. Relevant clinical laboratory abnormalities (e.g., sodium <130 mmol/L, alanine or
aspartate transaminases >2.0 times the upper limit of the normal, white blood cell
[WBC] count <3,000 cells/mm3) or for patients of Asian ancestry, positive HLA B*1502
test.
18. Estimated creatinine clearance <60 mL/min [men: (140-age) x weight/serum creatinine x
72; women: (0.85) (140-age) x weight/serum creatinine x 72. Age in years, weight in
kg, and serum creatinine in mg/dL].
19. Pregnant or nursing.
20. Participation in other drug clinical trial within the last 2 months or received an
investigational drug within 5 half-lives of this other product, whichever is longer.
Patient(s) who are known to have not taken any doses of study drug(s) in earlier
study(ies) (e.g. screen-failures) are allowed without any time limitation.
21. Not ensured capability to perform the trial.
22. Any other condition or circumstance that, in the opinion of the Investigator, may
compromise the patient's ability to comply with the study protocol.
23. Currently treated with VNS, but implanted <6 months before screening or parameters
not stable for at least 1 month prior to screening.
At V2 (randomisation), patients must not be/have:
24. Inadequate compliance to concomitant AEDs during the 8-week baseline period or to
screening exclusion criteria.
25. Inadequate completion of the study diary.
26. Any other condition or circumstance that, in the opinion of the Investigator, may
compromise the patient's ability to comply with the study protocol. |