Epilepsy
Conditions
Brief summary
Phase I, two-centre, open-label, randomized, gender-balanced, single-dose, laboratory blinded, two-period, two-sequence, crossover study in 2 groups of 20 healthy male and female subjects, to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL)
Detailed description
Phase I, two-centre, open-label, randomized, gender-balanced, single-dose, laboratory blinded, two-period, two-sequence, crossover study in 2 groups of 20 healthy male and female subjects. The study consisted in 2 periods separated by a wash-out of at least 7 days between doses. To demonstrate the bioequivalence (BE) between two active product ingredient (API) sources \[current API source - marketed formulation (MF) versus new API source - to-be-marketed (TBM)\] of eslicarbazepine acetate (ESL)
Interventions
DRUGBIA 2-093
MF - Marketed formulation
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
* A signed and dated informed consent form before any study-specific screening procedure was performed, * Healthy male or female 18 to 55 of age, inclusive, * Had a BMI within the range of 18 to 25 kg/m2 inclusive at screening, * Had a physical examination, vital signs, electrocardiogram (ECG) and routine laboratory tests within normal ranges or considered as non clinically significant (NCS) by the Investigator, * Non-smokers or smokers of less than 10 cigarettes per day, * If female, she was not of childbearing potential by reason of surgery (hysterectomy, bilateral oophorectomy or tubal ligation) or, if of childbearing potential, she had to be using one of the following effective method of contraception (intrauterine device (IUD) or abstention or condom) for the duration of the trial and had to have a negative urine pregnancy test at screening visit and upon each admission period.
Exclusion criteria
* Had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders, or have a clinically relevant surgical history, * Presented any disease or condition (medical or surgical) which, in the opinion of the Investigator, that may have interfered with the absorption, distribution, metabolism or excretion of study drug, * Had a history of relevant atopy or any drug hypersensitivity (including known hypersensitivity to eslicarbazepine acetate or any of its excipients), * Had a history of alcoholism or drug abuse within 1 year before D 1, * Consumption of more than 50 g of ethanol per day (12.5 Centiliters \[cL\] glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g), * Use of medicines within 2 weeks of admission to first treatment period that could affect, in the Investigator's opinion, the safety of the subject, * Had used any investigational drug or participated in any clinical trial within 2 months of admission to first treatment period, * Had donated or received any blood or blood products within 2 months prior to screening, * Could not communicate reliably with the investigator, was unlikely to co-operate with the requirements of the study, * Was unwilling or unable to give written informed consent, * If female, was pregnant or breast-feeding,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration | pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period | Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite |
| Tmax - Time of Occurrence of Cmax | pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period | Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite |
| AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period | Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 400 mg BIA 2-093 In Group 1, subjects received randomly on period 1 and 2, either a single 400 mg tablet of ESL (MF), or a single 400 mg tablet of ESL (TBM). | 20 |
| 800 mg BIA 2-093 In Group 2, subjects received randomly on period 1 and period 2, either a single 800 mg tablet of ESL (MF), or a single 800 mg dose of ESL (TBM). | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | 400 mg BIA 2-093 | 800 mg 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 | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 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 | 1 / 40 | 0 / 20 | 1 / 20 | 4 / 20 | 4 / 18 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 18 | 0 / 40 |
Outcome results
Primary
AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification
Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite
Time frame: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg BIA 2-093 | AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (BIA 2-005 Reference) | 112568 ng.hr/ml | Standard Deviation 23011 |
| 400 mg BIA 2-093 | AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (BIA 2-005 Test) | 108224 ng.hr/ml | Standard Deviation 23971 |
| 800 mg BIA 2-093 | AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (BIA 2-005 Reference) | 279035 ng.hr/ml | Standard Deviation 60183 |
| 800 mg BIA 2-093 | AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification | AUC0-t (BIA 2-005 Test) | 278734 ng.hr/ml | Standard Deviation 61738 |
Primary
Cmax - Maximum Plasma Concentration
Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite
Time frame: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg BIA 2-093 | Cmax - Maximum Plasma Concentration | Cmax (BIA 2-005 Reference) | 6461 ng/ml | Standard Deviation 1346 |
| 400 mg BIA 2-093 | Cmax - Maximum Plasma Concentration | Cmax (BIA 2-005 Test) | 6547 ng/ml | Standard Deviation 1524 |
| 800 mg BIA 2-093 | Cmax - Maximum Plasma Concentration | Cmax (BIA 2-005 Reference) | 13183 ng/ml | Standard Deviation 2564 |
| 800 mg BIA 2-093 | Cmax - Maximum Plasma Concentration | Cmax (BIA 2-005 Test) | 12988 ng/ml | Standard Deviation 2215 |
Primary
Tmax - Time of Occurrence of Cmax
Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite
Time frame: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 400 mg BIA 2-093 | Tmax - Time of Occurrence of Cmax | Tmax (BIA 2-005 Reference) | 2.00 hours |
| 400 mg BIA 2-093 | Tmax - Time of Occurrence of Cmax | Tmax (BIA 2-005 Test) | 2.00 hours |
| 800 mg BIA 2-093 | Tmax - Time of Occurrence of Cmax | Tmax (BIA 2-005 Reference) | 2.00 hours |
| 800 mg BIA 2-093 | Tmax - Time of Occurrence of Cmax | Tmax (BIA 2-005 Test) | 1.75 hours |