Epilepsy
Conditions
Keywords
Epilepsy, Oxcarbazepine, Eslicarbazepine Acetate, BIA 2-093
Brief summary
To investigate the steady-state pharmacokinetics of once-daily and twice-daily regimens of BIA 2-093 and twice-daily regimen of Oxcarbazepine (Trileptal®) in healthy subjects and to assess the tolerability of such regimens in healthy subjects.
Detailed description
Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of three 8-day treatment periods separated by washout periods of 10-15 days. On each of the treatment periods the volunteers received either a daily oral dose of BIA 2-093 900 mg once-daily (od), BIA 2-093 450 mg twice-daily (bid), or Oxcarbazepine (Trileptal®) 450 mg bid.
Interventions
DRUGBIA 2-093
DRUGOxcarbazepine
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 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects were eligible for entry into the study if they fulfilled the following inclusion criteria: * Male or female subjects aged between 18 and 45 years, inclusive. * Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive. * Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG. * Subjects who had clinical laboratory tests clinically acceptable. * Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening. * Subjects who were negative for alcohol and drugs of abuse at screening and first admission. * Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day. * Subjects who were able and willing to give written informed consent. * If case of female subjects, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, who used one of the following methods of contraception: double-barrier, intrauterine device or abstinence. * If case of female subjects, subjects who had a negative pregnancy test at screening and first admission.
Exclusion criteria
* Subjects who did not conform to the above inclusion criteria. * 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 atopy. * Subjects who had a history of hypersensitivity to carbamazepine or oxcarbazepine or any other 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 had a significant infection or known inflammatory process on screening and/or first admission. * Subjects who had acute gastrointestinal symptoms at the time of screening and/or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). * Subjects who had used prescription or over-the-counter medication within two weeks of first admission. * Subjects who had used any investigational drug and/or participated in any clinical trial within four months of their first admission. * Subjects who had previously received BIA 2-093. * Subjects who had donated and/or received any blood or blood products within the previous 4 months prior to screening. * Subjects who were vegetarians, vegans and/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. * In case of female subjects, subjects who were pregnant or breast-feeding. * In case of female subjects, subjects who were of childbearing potential and did not use an approved effective contraceptive method or used oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Drug Concentration | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose | Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC - Area Under the Plasma Concentration Versus Time Curve | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose | AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine |
| Number of of Subjects Reporting at Least One Adverse Event | 8 weeks | Number of of subjects reporting at least one adverse event. |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A BIA 2-093 450 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 450 mg bid | 4 |
| Group B BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 450 mg once-daily period BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 450 mg od | 4 |
| Group C oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 450 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 450 mg od - BIA 2-093 450 mg bid | 4 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group 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 | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 6 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 | 9 / 11 | 10 / 12 | 11 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Drug Concentration
Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
Population: The results are related to overall population in the study devided by period of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 900 mg od | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-195) | 685 ng/mL | Standard Deviation 188 |
| BIA 2-093 900 mg od | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-194) | 22210 ng/mL | Standard Deviation 7257 |
| BIA 2-093 900 mg od | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (Oxcarbazepine) | 208 ng/mL | Standard Deviation 53.2 |
| BIA 2-093 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-195) | 702 ng/mL | Standard Deviation 182 |
| BIA 2-093 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-194) | 16667 ng/mL | Standard Deviation 3981 |
| BIA 2-093 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (Oxcarbazepine) | 182 ng/mL | Standard Deviation 47.2 |
| Oxcarbazepine 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-194) | 12195 ng/mL | Standard Deviation 2053 |
| Oxcarbazepine 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (Oxcarbazepine) | 1080 ng/mL | Standard Deviation 548 |
| Oxcarbazepine 450 mg Bid | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-195) | 2481 ng/mL | Standard Deviation 362 |
Secondary
AUC - Area Under the Plasma Concentration Versus Time Curve
AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
Population: The results are related to overall population in the study devided by period of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 900 mg od | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-195) | 20164 ng*h/mL | Standard Deviation 6790 |
| BIA 2-093 900 mg od | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-194) | 381601 ng*h/mL | Standard Deviation 95368 |
| BIA 2-093 900 mg od | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (Oxcarbazepine) | 3238 ng*h/mL | Standard Deviation 1033 |
| BIA 2-093 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-195) | 19091 ng*h/mL | Standard Deviation 6042 |
| BIA 2-093 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-194) | 283014 ng*h/mL | Standard Deviation 74203 |
| BIA 2-093 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (Oxcarbazepine) | 2699 ng*h/mL | Standard Deviation 909 |
| Oxcarbazepine 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-194) | 268376 ng*h/mL | Standard Deviation 43294 |
| Oxcarbazepine 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (Oxcarbazepine) | 5196 ng*h/mL | Standard Deviation 1472 |
| Oxcarbazepine 450 mg Bid | AUC - Area Under the Plasma Concentration Versus Time Curve | AUC0-t (BIA 2-195) | 48841 ng*h/mL | Standard Deviation 9041 |
Secondary
Number of of Subjects Reporting at Least One Adverse Event
Number of of subjects reporting at least one adverse event.
Time frame: 8 weeks
Population: The results are related to overall population in the study devided by period of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIA 2-093 900 mg od | Number of of Subjects Reporting at Least One Adverse Event | 9 Subjects |
| BIA 2-093 450 mg Bid | Number of of Subjects Reporting at Least One Adverse Event | 10 Subjects |
| Oxcarbazepine 450 mg Bid | Number of of Subjects Reporting at Least One Adverse Event | 11 Subjects |