Epilepsy
Conditions
Brief summary
Single center, randomized, single dose, laboratory-blinded, 2-period, 2-sequence, crossover design
Detailed description
Single center, randomized, single dose, laboratory-blinded, 2-period, 2-sequence, crossover design to evaluate and compare the relative bioavailability and therefore the bioequivalence of three doses (400 mg, 600 mg and 800 mg) of eslicarbazepine acetate for two formulations (CTF versus TBM) after a single oral dose administration under fasting conditions
Interventions
DRUGBIA 2-093
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer * Male or female aged of at least 18 years but not older than 55 years with a body mass index (BMI) greater than or equal to equal to 19 and below 30 kg/m2 * Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance (laboratory tests are presented in section 6.1.1.3) * Healthy according to the medical history, laboratory results and physical examination * Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An exsmoker is defined as someone who completely stopped smoking for at least 12 months before day 1 of this study
Exclusion criteria
* Significant history of hypersensitivity to eslicarbazepine, oxcarbazepine, carbamazepine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs * Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects * History of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, including but not limited to cholecystectomy * Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease * Presence of significant heart disease or disorder according to ECG * Presence or history of significant central nervous system disorder like convulsion or depression * Participation in any previous study with eslicarbazepine acetate * Females who are pregnant according to a positive serum pregnancy test or are lactating * Females of childbearing potential who refuse to use an acceptable contraceptive regimen throughout the study * Use of systemic contraceptives (oral, implant, etc.) in the previous 14 days before day 1 of this study and until study completion. * Use of systemic contraceptives (injections) and hormonal replacement therapy in the previous 13 weeks before day 1 of this study and until study completion * Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) * Any clinically significant illness in the previous 28 days before day 1 of this study * Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin and rifampin), in the previous 28 days before Day 1 of this study * Participation in another clinical trial or donation of 50 mL or more of blood in the previous 28 days before day 1 of this study * Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study * Positive urine screening of drugs of abuse (drugs listing is presented in section 6.1.1.4) * Any history of tuberculosis and/or prophylaxis for tuberculosis * Positive results to HIV, HBsAg or anti-HCV tests
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration |
| AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration |
| Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A:BIA 2-093 400 mg One Eslicarbazepine acetate (BIA 2-093) 400 mg tablet (To-Be-Marketed Formulation, TBM)
One Eslicarbazepine acetate (BIA 2-093) 400 mg tablet (Clinical Trial Formulation, CTF)
BIA 2-093 | 20 |
| Cohort B:BIA 2-093 600 mg One Eslicarbazepine acetate (BIA 2-093) 600 mg tablet (To-Be-Marketed Formulation, TBM)
One Eslicarbazepine acetate (BIA 2-093) 600 mg tablet (Clinical Trial Formulation, CTF)
BIA 2-093 | 20 |
| Cohort C:BIA 2-093 800 mg One Eslicarbazepine acetate (BIA 2-093) 800 mg tablet (To-Be-Marketed Formulation, TBM)
One Eslicarbazepine acetate (BIA 2-093) 800 mg tablet (Clinical Trial Formulation, CTF)
BIA 2-093 | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Cohort A:BIA 2-093 400 mg | Cohort B:BIA 2-093 600 mg | Cohort C:BIA 2-093 800 mg | 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 | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 20 | 8 / 19 | 8 / 20 | 9 / 20 | 6 / 20 | 9 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time
Time frame: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A:BIA 2-093 400 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Test | 125739.8 ng.h/mL | Standard Deviation 29045.7 |
| Cohort A:BIA 2-093 400 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Reference | 122134.1 ng.h/mL | Standard Deviation 27602.3 |
| Cohort B:BIA 2-093 600 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Test | 219560.8 ng.h/mL | Standard Deviation 39740.5 |
| Cohort B:BIA 2-093 600 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Reference | 215750.4 ng.h/mL | Standard Deviation 44444.6 |
| Cohort C:BIA 2-093 800 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Test | 294749.1 ng.h/mL | Standard Deviation 48044.1 |
| Cohort C:BIA 2-093 800 mg | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-093) Reference | 293959.9 ng.h/mL | Standard Deviation 49385.3 |
Primary
Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005
Time frame: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A:BIA 2-093 400 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Test | 7107.7 ng/mL | Standard Deviation 2004.4 |
| Cohort A:BIA 2-093 400 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Reference | 6660.3 ng/mL | Standard Deviation 1545.2 |
| Cohort B:BIA 2-093 600 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Test | 10724.8 ng/mL | Standard Deviation 1941.2 |
| Cohort B:BIA 2-093 600 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Reference | 10404.5 ng/mL | Standard Deviation 1716.7 |
| Cohort C:BIA 2-093 800 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Test | 13186.4 ng/mL | Standard Deviation 2307.6 |
| Cohort C:BIA 2-093 800 mg | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 | Cmax (BIA 2-005) Reference | 12767.6 ng/mL | Standard Deviation 2528 |
Primary
Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005
Time frame: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Cohort A:BIA 2-093 400 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Test | 2.00 hours | Standard Deviation 0.89 |
| Cohort A:BIA 2-093 400 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Reference | 2.50 hours | Standard Deviation 1.24 |
| Cohort B:BIA 2-093 600 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Test | 2.50 hours | Standard Deviation 1.21 |
| Cohort B:BIA 2-093 600 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Reference | 3.00 hours | Standard Deviation 1.3 |
| Cohort C:BIA 2-093 800 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Test | 3.00 hours | Standard Deviation 1.64 |
| Cohort C:BIA 2-093 800 mg | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 | Tmax (BIA 2-005) Reference | 3.00 hours | Standard Deviation 1.31 |