Epilepsy
Conditions
Brief summary
Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects.
Detailed description
Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects. The study consisted of 3 periods separated by a washout of 7 days or more between doses. Subjects received a single oral 800 mg dose of eslicarbazepine acetate following a standard meal in one period, and following at least 10 hours of fasting in two periods.
Interventions
DRUGBIA 2-093
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects aged between 18 and 55 years, inclusive. * Subjects of body mass index (BMI, kg/m2) within the normal range \[4\], i.e., between 18.50 and 24.99, inclusive. * Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead ECG. * Subjects who had clinical laboratory test results clinically acceptable at screening and admission to first treatment period. * Subjects who had negative tests for HBsAg, anti-HCVAb and anti- HIV-1 and HIV-2 Ab at screening. * Subjects who had a negative screen for alcohol and drugs of abuse at screening. * Subjects who were non-smokers or ex-smokers who discontinued smoking at least 3 months prior to admission. * Subjects who were able and willing to give written informed consent. * (If female) She was not of childbearing potential by reason of surgery (hysterectomy or tubal ligation) or, if of childbearing potential, she used one of the following methods of contraception: intrauterine device (by the study subject) + condom (by the partner), diaphragm (by the study subject) + condom (by the partner), or spermicide (by the study subject) + condom (by the partner). * (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.
Exclusion criteria
* Subjects who did not conform to the above inclusion criteria, or * Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders. * Subjects who had a clinically relevant surgical history. * Subjects who had a clinically relevant family history. * Subjects who had a history of relevant drug hypersensitivity. * Subjects who had a history of alcoholism or drug abuse. * Subjects who consumed more than 14 units of alcohol a week. * Subjects who used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments. * Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission. * Subjects who had previously received eslicarbazepine acetate (ESL, BIA 2-093). * Subjects who donated or received any blood or blood products within the previous 2 months prior to screening. * Subjects who were vegetarians, vegans or have medical dietary restrictions. * Subjects who could not communicate reliably with the investigator. * Subjects who were unlikely to co-operate with the requirements of the study. * Subjects who were unwilling or unable to give written informed consent. * (If female) She was pregnant or breast-feeding. * (If female) She was of childbearing potential and she did not used and approved effective contraceptive method or she used oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (BIA 2-005) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | Cmax (BIA 2-005) - maximum observed plasma drug concentration of BIA 2-005 (BIA 2-093 metabolite) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t (BIA 2-005) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | AUC0-t (BIA 2-005) - the area under the plasma concentration-time curve from time zero to the last sampling time at which BIA 2-005 concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule (BIA 2-005 is a BIA 2-093 metabolite) |
| Tmax (BIA 2-005) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | tmax (BIA 2-005) - the time of occurrence of Cmax of BIA 2-005 (BIA 2-005 is a BIA 2-093 metabolite) |
| AUC0-∞ (BIA 2-005) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | AUC0-∞ (BIA 2-005) - the area under the plasma BIA 2-005 concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant; (BIA 2-005 is a BIA 2-093 metabolite) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence A Period 1 - ESL 800 mg, in fasting Period 2 - ESL 800 mg, in fed Period 3 - ESL 800 mg (2x400mg), in fasting | 6 |
| Sequence B Period 1 - ESL 800 mg (2x400mg), in fasting Period 2 - ESL 800 mg, in fasting Period 3 - ESL 800 mg, in fed | 6 |
| Sequence C Period 1 - ESL 800 mg, in fed Period 2 - ESL 800 mg (2x400mg), in fasting Period 3 - ESL 800 mg, in fasting | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Pregnancy | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence A | Sequence B | Sequence C | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 9 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 | 3 / 18 | 2 / 17 | 2 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Cmax (BIA 2-005)
Cmax (BIA 2-005) - maximum observed plasma drug concentration of BIA 2-005 (BIA 2-093 metabolite)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 800 mg Fasting | Cmax (BIA 2-005) | 10973 ng/mL | Standard Deviation 2628 |
| BIA 2-093 800 mg Fed | Cmax (BIA 2-005) | 11044 ng/mL | Standard Deviation 2495 |
| BIA 2-093 800 mg (2 x 400 mg) | Cmax (BIA 2-005) | 11022 ng/mL | Standard Deviation 2748 |
Secondary
AUC0-∞ (BIA 2-005)
AUC0-∞ (BIA 2-005) - the area under the plasma BIA 2-005 concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant; (BIA 2-005 is a BIA 2-093 metabolite)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 800 mg Fasting | AUC0-∞ (BIA 2-005) | 243808 ng.h/mL | Standard Deviation 50464 |
| BIA 2-093 800 mg Fed | AUC0-∞ (BIA 2-005) | 236089 ng.h/mL | Standard Deviation 50764 |
| BIA 2-093 800 mg (2 x 400 mg) | AUC0-∞ (BIA 2-005) | 244821 ng.h/mL | Standard Deviation 48873 |
Secondary
AUC0-t (BIA 2-005)
AUC0-t (BIA 2-005) - the area under the plasma concentration-time curve from time zero to the last sampling time at which BIA 2-005 concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule (BIA 2-005 is a BIA 2-093 metabolite)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 800 mg Fasting | AUC0-t (BIA 2-005) | 241651 ng.h/mL | Standard Deviation 50381 |
| BIA 2-093 800 mg Fed | AUC0-t (BIA 2-005) | 234092 ng.h/mL | Standard Deviation 50510 |
| BIA 2-093 800 mg (2 x 400 mg) | AUC0-t (BIA 2-005) | 242375 ng.h/mL | Standard Deviation 48599 |
Secondary
Tmax (BIA 2-005)
tmax (BIA 2-005) - the time of occurrence of Cmax of BIA 2-005 (BIA 2-005 is a BIA 2-093 metabolite)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 800 mg Fasting | Tmax (BIA 2-005) | 2.64 hours | Standard Deviation 1.65 |
| BIA 2-093 800 mg Fed | Tmax (BIA 2-005) | 2.75 hours | Standard Deviation 2.31 |
| BIA 2-093 800 mg (2 x 400 mg) | Tmax (BIA 2-005) | 2.56 hours | Standard Deviation 1.58 |