Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Effect of BIA 9-1067 on the Pharmacokinetics and Pharmacodynamics of Warfarin

Summary: The purpose of this study is to investigate CYP2C9 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of S-warfarin, a substrate of CYP2C9.

Detailed description: Single-centre, open-label, randomised, two-way crossover study in healthy young male and female volunteers. The study was to consist of 2 treatment periods separated by a washout period of 14 days or more. In one period, subjects were to receive a single-dose of 25 mg BIA 9-1067 with a single-dose of racemic 25 mg warfarin. In the other period, a 25 mg warfarin single-dose was to be administered alone.

Eligibility: Inclusion Criteria:
  -  Able and willing to give written informed consent.
  -  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.
  -  Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
  -  Clinical laboratory test results clinically acceptable at screening and admission to each treatment period.
  -  Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.
  -  Non-smokers or ex-smokers for at least 3 months.
  -  (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 or intrauterine device.
  -  (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.
  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 have affected the safety or other study assessments, in the investigator's opinion.
  -  Had previously received BIA 9-1067.
  -  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.
  -  Employees at BIAL - Portela & Co, SA.
  -  (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 or intra-uterine device) or she used oral contraceptives.

Relevance to patient case: not relevant