Epilepsy
Conditions
Brief summary
Single centre, two-way crossover, randomised, open-label study in 20 healthy female volunteers.The volunteers received an oral single-dose of a combined contraceptive containing with an oral once daily dose of 1200 mg of BIA 2-093
Detailed description
Single centre, two-way crossover, randomised, open-label study in 20 healthy female volunteers.The volunteers received an oral single-dose of a combined contraceptive containing 30 μg ethinyloestradiol and 150 μg levonorgestrel on two occasions - once as such and once after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 for 15 days separated by a washout period of at least 3 weeks.
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 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Pre-menopausal female; * Able and willing to give written informed consent; * Aged 18 to 40 years, inclusive; * Not pregnant or breast-feeding; * Body mass index (BMI) between 19 and 30 kg/m2, inclusive; * Healthy as determined by medical history, physical examination, complete neurological examination, vital signs, and 12-lead ECG; * Clinical laboratory tests with clinically acceptable results at screening and admission to the first period; * Negative tests for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab at screening; * Negative test for drugs of abuse at screening; * Non-smoker or smokes less than 10 cigarettes or equivalent per day; * Agreed to either practice abstinence or use a double-barrier or intra-uterine device from screening until the follow-up visit; * Negative pregnancy test at screening and admission to the first period.
Exclusion criteria
* Had any contra-indication to the use of oral contraceptives; * Had experienced notable adverse events while on any oral contraceptive; * Had a history of alcoholism or drug abuse; * Had a relevant history or presence of respiratory, gastrointestinal, renal, hepatic,haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders; * Had acute gastrointestinal symptoms at the time of screening or admission to the first period; * Had a significant infection or inflammatory process at the time of screening or admission to the first period; * Had a relevant surgical history; * Had a relevant family history; * Had a history of relevant drug hypersensitivity (e.g., carbamazepine or oxcarbazepine); * Had used relevant prescription or over-the-counter medication within 2 weeks ofadmission to the first period; * Consumed more than 14 units of alcohol a week; * Had participated in any clinical trial within 3 months prior to screening; * Had previously received BIA 2-093; * Had donated or received any blood or blood products within 2 months prior to screening; * Was unlikely to co-operate with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily. | Cmax - Maximum observed plasma BIA 2-194 concentration on days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period. | Cmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) |
| Tmax | pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period. | Tmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) |
| AUC0-t | pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period. | AUC0-t (ng.h/mL) following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days followed by washout and 3 days of oral single-dose contraceptive
BIA 2-093
Contraceptives, Oral, Combined | 10 |
| Treatment Sequence B oral single-dose of a contraceptive for 3 days after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days
BIA 2-093
Contraceptives, Oral, Combined | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment Sequence A | Treatment Sequence B | 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 | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 5 / 18 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 |
Outcome results
Primary
Cmax - Maximum Observed Plasma BIA 2-194 Concentration
Cmax - Maximum observed plasma BIA 2-194 concentration on days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.
Time frame: Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 2 | 8443 ng/mL | Standard Deviation 1422 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 4 | 10691 ng/mL | Standard Deviation 1736 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 6 | 10961 ng/mL | Standard Deviation 1737 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 8 | 10175 ng/mL | Standard Deviation 996 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 10 | 10332 ng/mL | Standard Deviation 1470 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 12 | 10821 ng/mL | Standard Deviation 1806 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 14 | 10670 ng/mL | Standard Deviation 1447 |
| Cmax (BIA 2-194) | Cmax - Maximum Observed Plasma BIA 2-194 Concentration | Day 15 | 9978 ng/mL | Standard Deviation 1452 |
Secondary
AUC0-t
AUC0-t (ng.h/mL) following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time frame: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cmax (BIA 2-194) | AUC0-t | AUC0-t (ethinyloestradiol) Test | 347 pg.h/mL | Standard Deviation 145 |
| Cmax (BIA 2-194) | AUC0-t | AUC0-t (ethinyloestradiol) Reference | 595 pg.h/mL | Standard Deviation 639 |
| Cmax (BIA 2-194) | AUC0-t | AUC0-t (Levonorgestrel) Test | 24000 pg.h/mL | Standard Deviation 12100 |
| Cmax (BIA 2-194) | AUC0-t | AUC0-t (Levonorgestrel) Reference | 33600 pg.h/mL | Standard Deviation 20000 |
Secondary
Cmax
Cmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time frame: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cmax (BIA 2-194) | Cmax | Cmax (ethinyloestradiol) Test | 53.4 pg/mL | Standard Deviation 17.9 |
| Cmax (BIA 2-194) | Cmax | Cmax (ethinyloestradiol) Reference | 66.1 pg/mL | Standard Deviation 19.1 |
| Cmax (BIA 2-194) | Cmax | Cmax (Levonorgestrel) Test | 3220 pg/mL | Standard Deviation 1330 |
| Cmax (BIA 2-194) | Cmax | Cmax (Levonorgestrel) Reference | 3720 pg/mL | Standard Deviation 1540 |
Secondary
Tmax
Tmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time frame: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cmax (BIA 2-194) | Tmax | tmax (ethinyloestradiol) Test | 1.67 h | Standard Deviation 0.53 |
| Cmax (BIA 2-194) | Tmax | tmax (ethinyloestradiol) Reference | 1.52 h | Standard Deviation 0.21 |
| Cmax (BIA 2-194) | Tmax | tmax (Levonorgestrel) Test | 1.28 h | Standard Deviation 0.49 |
| Cmax (BIA 2-194) | Tmax | tmax (Levonorgestrel) Reference | 1.21 h | Standard Deviation 0.36 |