The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin

Study Overview
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Brief Summary
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Multiple-dose, open-label, single-period study consisting of three consecutive phases

Detailed Description
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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

Official Title
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The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin in Healthy Volunteers

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Phase A: Warfarin Phase B: Warfarin + BIA 2-093 (ESL) Phase C: Warfarin | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Warfarin<br> <br> * Other names: Uniwarfin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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. |