Partial Epilepsy
Conditions
Keywords
Partial, Epilepsy, Eslicarbazepine acetate, Combined oral contraceptive, Pharmacokinetics, Tolerability
Brief summary
The purpose of this study is to investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics and tolerability of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Interventions
DRUGeslicarbazepine acetate and Microginon®
eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
DRUGMicroginon®
Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Pre-menopausal female subjects * Age 18-40 years, inclusive * Body mass index (BMI) 19-30 kg/m2, inclusive * Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG * Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening * Negative urine pregnancy test at screening and admission to each treatment period. * Using one of the following methods of contraception: double barrier or intrauterine device
Exclusion criteria
* Subjects who have any contra-indication to the use of oral contraceptives * History or presence of clinically relevant diseases, disorders or surgical history * History of alcoholism or drug abuse * Have used medicines within two weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Concentration | 15-day | To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | 15-day | To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). |
| AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | 15-day | To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ESL and Microginon® 15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive.
eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period.
Microginon®: single oral dose on day 14 of treatment period | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | ESL and Microginon® |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 20 | 8 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Concentration
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time frame: 15-day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microginon® | Cmax - Maximum Observed Plasma Concentration | Cmax (ethinyloestradiol) | 82.4 pg/mL | Standard Deviation 23.4 |
| Microginon® | Cmax - Maximum Observed Plasma Concentration | Cmax (levonogestrel) | 4170 pg/mL | Standard Deviation 1720 |
| ESL and Microginon® | Cmax - Maximum Observed Plasma Concentration | Cmax (ethinyloestradiol) | 75.0 pg/mL | Standard Deviation 26.8 |
| ESL and Microginon® | Cmax - Maximum Observed Plasma Concentration | Cmax (levonogestrel) | 4340 pg/mL | Standard Deviation 1530 |
Secondary
AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time frame: 15-day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microginon® | AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | AUC0-∞ (ethinyloestradiol) | 0.768 ng.h/mL | Standard Deviation 0.223 |
| Microginon® | AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | AUC0-∞ (levonorgestrel) | 52.1 ng.h/mL | Standard Deviation 22.1 |
| ESL and Microginon® | AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | AUC0-∞ (ethinyloestradiol) | 0.533 ng.h/mL | Standard Deviation 0.181 |
| ESL and Microginon® | AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | AUC0-∞ (levonorgestrel) | 43.1 ng.h/mL | Standard Deviation 13.3 |
Secondary
AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time frame: 15-day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microginon® | AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (ethinyloestradiol) | 0.665 ng.h/mL | Standard Deviation 0.195 |
| Microginon® | AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (levonogestrel) | 37.4 ng.h/mL | Standard Deviation 19.1 |
| ESL and Microginon® | AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (ethinyloestradiol) | 0.453 ng.h/mL | Standard Deviation 0.167 |
| ESL and Microginon® | AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (levonogestrel) | 32.0 ng.h/mL | Standard Deviation 12.9 |