Epilepsy
Conditions
Brief summary
Multiple-dose, open-label, single-period study consisting of three consecutive phases
Detailed description
Multiple-dose, open-label, single-period study consisting of three consecutive phases: Phase A - run-in warfarin dose-finding phase Phase B - warfarin pharmacokinetics (PK) and international normalised ratio (INR) profiling Phase C - warfarin alone at their individualised doses
Interventions
DRUGBIA 2-093
DRUGWarfarin
Sponsors
Bial - Portela C S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 clinically acceptable * Subjects who were negative for HBs Ag, anti-HCV Ab and anti-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 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 or intrauterine device * In case of female volunteers, subjects who had a negative pregnancy test at screening
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, endocrine, connective tissue diseases or disorders * Subjects who had a current haemostatic disorder or a personal or family history of any such disorder * Subjects who had a personal or family history of bleeding complications after surgery or tooth extraction, nose or gingival bleeding, or haemorrhagic diathesis. * Subjects with a profession or activities implying a special risk of trauma * Subjects with any abnormality in the coagulation status (aPTT or prothrombin INR) * 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 14 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 2 weeks prior admission on Phase A * Subjects who had used any investigational drug and/or participated in any clinical trial within 2 months prior admission to Phase A * 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 admission to Phase A * Subjects who were vegetarians, vegans and/or had medical dietary restrictions * Subjects who could not communicate reliably with the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax - Maximum Steady-state Plasma Concentration | PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose. |
Secondary
| Measure | Time frame |
|---|---|
| Tmax - Time of Occurrence of Cmax | PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose. |
| AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval | PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Phase A: Warfarin Phase B: Warfarin + BIA 2-093 (ESL) Phase C: Warfarin
BIA 2-093
Warfarin | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Group 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Cmax - Maximum Steady-state Plasma Concentration
Time frame: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Cmax - Maximum Steady-state Plasma Concentration | 31652 ng/mL | Standard Deviation 11150 |
Secondary
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval
Time frame: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval | 411834 ng.h/mL | Standard Deviation 113305 |
Secondary
Tmax - Time of Occurrence of Cmax
Time frame: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Tmax - Time of Occurrence of Cmax | 6 hours |