Epilepsy
Conditions
Brief summary
Single centre, open-label, randomised, three-way crossover study in 18 healthy subjects (9 males and 9 females). The study consisted of three consecutive single-dose treatment periods separated by a washout period of 7 days or more. On each treatment period, the volunteers received a single dose of BIA 2-093 800 mg, orally.
Detailed description
Sample size (planned and analyzed): It was planned to have at least 16 healthy subjects completed and evaluable. Taking into account the potential occurrence of dropouts, two additional subjects were to be recruited and entered the study. Therefore, a total of 18 subjects were enrolled. Diagnosis and main selection criteria: Healthy male or female volunteers aged between 18 and 45 years, with body mass index between 19 and 28 kg/m2, non-smokers or smoking less than 10 cigarettes or equivalent per day.
Interventions
DRUGBIA 2-093
oral suspension 50 mg/mL
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, vital signs and 12-lead ECG at screening. * Subjects who had clinical laboratory tests clinically acceptable at screening. * 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. * Subjects who were non-smokers or who smoke less than 10 cigarettes or equivalent per day. * Subjects who were able and willing to give written informed consent. * (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: doublebarrier, intra-uterine device or abstinence. * (If female) She had a negative pregnancy test at screening and admission to each study period.
Exclusion criteria
* Subjects who do not conform to the above inclusion criteria, or * Subjects who have 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 have a clinically relevant surgical history. * Subjects who have a clinically relevant family history. * Subjects who have a history of relevant atopy. * Subjects who have a history of any drug hypersensitivity. * Subjects who have a history of alcoholism or drug abuse. * Subjects who consume more than 14 units of alcohol a week. * Subjects who have a significant infection or known inflammatory process on screening and/or first admission. * Subjects who have acute gastrointestinal symptoms at the time of screening and/or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). * Subjects who have used medicines within 2 weeks of admission to first period. * Subjects who have participated in any clinical trial within 3 months prior to screening. * Subjects who have previously received BIA 2-093. * Subjects who have donated and/or received any blood or blood products within the previous 3 months prior to screening. * Subjects who are vegetarians, vegans and/or have medical dietary restrictions. * Subjects who cannot communicate reliably with the investigation team. * Subjects who are unlikely to co-operate with the requirements of the study. * Subjects who are unwilling or unable to give written informed consent. * (If female) She is pregnant or breast-feeding. * (If female) She is of childbearing potential and she does not use an approved effective contraceptive method or she uses oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - the Maximum Plasma Concentration | Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose | Cmax - the maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005 |
| Tmax - the Time of Occurrence of Cmax | Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose | Tmax - the Time of Occurrence of maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005 |
| AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time of BIA 2-093 metabolite: BIA 2-005 |
| AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity of BIA 2-093 metabolite: BIA 2-005 |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A 1. st period - 16 mL oral suspension 50 mg/mL
2. nd period - Four 200 mg tablets
3. rd period - One 800 mg tablet | 6 |
| Group B 1. st period - One 800 mg tablet
2. nd period - 16 mL oral suspension 50 mg/mL
3. rd period - Four 200 mg tablets | 6 |
| Group C 1. st period - Four 200 mg tablets
2. nd period - One 800 mg tablet
3. rd period - 16 mL oral suspension 50 mg/mL | 6 |
| Total | 18 |
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 | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 1 / 18 | 0 / 18 | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity of BIA 2-093 metabolite: BIA 2-005
Time frame: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | 325732 ng*h/mL | Standard Deviation 64898 |
| BIA 2-093 - Four 200 mg Tablets | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | 304219 ng*h/mL | Standard Deviation 66045 |
| BIA 2-093 One 800 mg Tablet | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity | 301065 ng*h/mL | Standard Deviation 59957 |
Primary
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time of BIA 2-093 metabolite: BIA 2-005
Time frame: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | 323277 ng*h/mL | Standard Deviation 64055 |
| BIA 2-093 - Four 200 mg Tablets | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | 302026 ng*h/mL | Standard Deviation 65270 |
| BIA 2-093 One 800 mg Tablet | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time | 299016 ng*h/mL | Standard Deviation 58806 |
Primary
Cmax - the Maximum Plasma Concentration
Cmax - the maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005
Time frame: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | Cmax - the Maximum Plasma Concentration | 18048 ng/mL | Standard Deviation 4644 |
| BIA 2-093 - Four 200 mg Tablets | Cmax - the Maximum Plasma Concentration | 16007 ng/mL | Standard Deviation 4008 |
| BIA 2-093 One 800 mg Tablet | Cmax - the Maximum Plasma Concentration | 17042 ng/mL | Standard Deviation 4131 |
Primary
Tmax - the Time of Occurrence of Cmax
Tmax - the Time of Occurrence of maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005
Time frame: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | Tmax - the Time of Occurrence of Cmax | 2 hours |
| BIA 2-093 - Four 200 mg Tablets | Tmax - the Time of Occurrence of Cmax | 3 hours |
| BIA 2-093 One 800 mg Tablet | Tmax - the Time of Occurrence of Cmax | 3 hours |