Clinical trial NCT02287415: The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin
Official title: The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2014-11-10
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Cmax - Maximum Steady-state Plasma Concentration
timeFrame: 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 outcomes:
measure: Tmax - Time of Occurrence of Cmax
timeFrame: 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.
measure: AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval
timeFrame: 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.
Other outcomes:
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