Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin
Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin
The purpose of this study is to determine whether multiple-dose administration of nebicapone
 affects the pharmacokinetics of warfarin.
Study design and methodology:

 This was a single-centre, open-label, randomised, two-way crossover study in healthy young
 male and female volunteers. The study consisted of 2 treatment periods separated by a washout
 period of 14 days or more. In one period, subjects received nebicapone 200 mg thrice-daily
 (tid) for 9 days, and a warfarin 25 mg single-dose concomitantly with the morning dose of
 nebicapone on Day 4. In the other period, a warfarin 25 mg single-dose was administered
 alone. Warfarin pharmacokinetic and pharmacodynamic profiles were characterised following
 warfarin dosing.
Inclusion Criteria:

 Subjects were eligible for entry into the study if they fulfilled the following inclusion
 criteria:

 -  Male or female subjects aged between 18 and 45 years, inclusive.

 -  Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.

 -  Healthy as determined by pre-study medical history, physical examination, vital signs,
 complete neurological examination and 12-lead ECG.

 -  Clinical laboratory test results clinically acceptable at screening and admission to
 first treatment period.

 -  Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.

 -  Negative screen for alcohol and drugs of abuse at screening and admission to each
 treatment period.

 -  Non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.

 -  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: double
 barrier, intrauterine device or abstinence.

 -  (If female) She had a negative urine pregnancy test at screening and admission to each
 treatment period.

 Exclusion Criteria:

 Subjects were not eligible for entry into the study if they fulfilled the following
 exclusion criteria:

 -  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.

 -  Clinically relevant surgical history.

 -  Personal or family history of haemostatic disorder.

 -  Personal or family history of bleeding complications after surgery or tooth
 extraction, nose or gingival bleeding, or haemorrhagic diathesis.

 -  Any abnormality in the coagulation tests.

 -  Any abnormality in the liver function tests.

 -  A history of relevant atopy or drug hypersensitivity.

 -  History of alcoholism or drug abuse.

 -  Consumed more than 14 units of alcohol a week.

 -  Significant infection or known inflammatory process at screening or admission to each
 treatment period.

 -  Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the
 time of screening or admission to each treatment period.

 -  Had used medicines within 2 weeks of admission to first period that may affect the
 safety or other study assessments, in the investigator's opinion.

 -  Had previously received BIA 3-202.

 -  Had used any investigational drug or participated in any clinical trial within 6
 months prior to screening.

 -  Had participated in more than 2 clinical trials within the 12 months prior to
 screening.

 -  Had donated or received any blood or blood products within the 3 months prior to
 screening.

 -  Vegetarians, vegans or had medical dietary restrictions.

 -  Cannot communicate reliably with the investigator.

 -  Unlikely to co-operate with the requirements of the study.

 -  Unwilling or unable to gave written informed consent.

 -  (If female) She was pregnant or breast-feeding.

 -  (If female) She was of childbearing potential and she did not used an approved
 effective contraceptive method (double-barrier, intra-uterine device or abstinence) or
 she used oral contraceptives.