Epilepsy
Conditions
Keywords
Eslicarbazepine acetate, Epilepsy, Oxcarbazepine
Brief summary
To investigate the pharmacokinetics of a single 900 mg oral dose of BIA 2-093 and a single 900 mg oral dose of Oxcarbazepine in healthy volunteers and to assess the tolerability of a single 900 mg dose of BIA 2-093 and Oxcarbazepine.
Detailed description
Single centre, open label, balanced randomised, two-way crossover study in 12 healthy volunteers. The study consisted of 2 periods separated by a washout period of 7 days or more. On each of the study periods the volunteers received either a single 900 mg oral dose of BIA 2-093 or a single 900 mg oral dose of Oxcarbazepine.
Interventions
DRUGBIA 2-093
Tablets containing BIA 2-093 in doses of 300 and 600 mg
DRUGOxcarbazepine
Tablets containing 300 mg and 600 mg of Trileptal®
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
* 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 acceptable. * Subjects who were negative for HBs Ag, 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 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. * In case of female volunteers, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, used one of the following methods of contraception: double-barrier, intrauterine device or abstinence. * In case of female volunteers, subjects who had a negative pregnancy test at screening and 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, 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 relevant drug hypersensitivity. * Subjects who had a history of alcoholism or drug abuse. * Subjects who consumed more than 21 units of alcohol a week. * Subjects who had a significant infection or known inflammatory process on screening and/or admission. * Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn). * Subjects who had used prescription drugs within 4 weeks of first dosing. * Subjects who had used over-the-counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing. * Subjects who had used any investigational drug and/or participated in any clinical trial within 2 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 2 months prior to screening. * Subjects who were vegetarians, vegans and/or had 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 volunteers, subjects who were pregnant or breast-feeding. * In case of female volunteers, 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 |
|---|---|---|
| Maximum Drug Concentration (Cmax) | at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose | Maximum observed plasma concentration (Cmax) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) | at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose | Area under the plasma concentration versus time curve (AUC) to last measurable time point (AUC0-t) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total of Subjects Reporting at Least One Adverse Event | 4 weeks | Monitoring of Adverse Events throughout the study: Safety was evaluated from the number of reported adverse events (AEs) by patient |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Period 1 - BIA 2-093; Period 2 - Oxcarbazepine Period 1 - Subjects recieved 900 mg of BIA 2-093 Period 2 - Subjects recieved 900 mg of oxcarbazepine | 6 |
| Period 1 - Oxcarbazepine; Period 2 - BIA 2-093 Period 1 - Subjects recieved 900 mg of oxcarbazepine Period 2 - Subjects recieved 900 mg of BIA 2-093 | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Period 1 - BIA 2-093; Period 2 - Oxcarbazepine | Period 1 - Oxcarbazepine; Period 2 - BIA 2-093 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 12 | 10 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Maximum Drug Concentration (Cmax)
Maximum observed plasma concentration (Cmax) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine.
Time frame: at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
Population: Values are described for single dose of BIA 2-093 or oxcarbazepine respectively for Group 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (BIA 2-194) | 15753 ng/mL | Standard Deviation 3781 |
| BIA 2-093 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (BIA 2-195) | 428 ng/mL | Standard Deviation 88.6 |
| BIA 2-093 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (Oxcarbazepine) | 140 ng/mL | Standard Deviation 37.7 |
| Oxcarbazepine 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (BIA 2-194) | 5978 ng/mL | Standard Deviation 1136 |
| Oxcarbazepine 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (BIA 2-195) | 1708 ng/mL | Standard Deviation 751 |
| Oxcarbazepine 900 mg od | Maximum Drug Concentration (Cmax) | Cmax (Oxcarbazepine) | 1268 ng/mL | Standard Deviation 656 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the plasma concentration versus time curve (AUC) to last measurable time point (AUC0-t) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine.
Time frame: at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
Population: Values are described for single dose of BIA 2-093 or oxcarbazepine respectively for Group 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (BIA 2-194) | 299065 ng*h/mL | Standard Deviation 65077 |
| BIA 2-093 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (BIA 2-195) | 13877 ng*h/mL | Standard Deviation 2867 |
| BIA 2-093 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (Oxcarbazepine) | 1821 ng*h/mL | Standard Deviation 693 |
| Oxcarbazepine 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (BIA 2-194) | 214433 ng*h/mL | Standard Deviation 45162 |
| Oxcarbazepine 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (BIA 2-195) | 49124 ng*h/mL | Standard Deviation 18926 |
| Oxcarbazepine 900 mg od | Area Under the Plasma Concentration Versus Time Curve (AUC) | AUC0-t (Oxcarbazepine) | 6549 ng*h/mL | Standard Deviation 3927 |
Other Pre-specified
Total of Subjects Reporting at Least One Adverse Event
Monitoring of Adverse Events throughout the study: Safety was evaluated from the number of reported adverse events (AEs) by patient
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIA 2-093 900 mg od | Total of Subjects Reporting at Least One Adverse Event | All treatment-emergent AEs | 6 subjects reporting at least 1 AE |
| BIA 2-093 900 mg od | Total of Subjects Reporting at Least One Adverse Event | Possibly related to treatment AEs | 5 subjects reporting at least 1 AE |
| Oxcarbazepine 900 mg od | Total of Subjects Reporting at Least One Adverse Event | All treatment-emergent AEs | 6 subjects reporting at least 1 AE |
| Oxcarbazepine 900 mg od | Total of Subjects Reporting at Least One Adverse Event | Possibly related to treatment AEs | 4 subjects reporting at least 1 AE |