Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin
- Registration Number
- NCT02779348
- Lead Sponsor
- Bial - Portela C S.A.
- Brief Summary
The purpose of this study is to determine whether multiple-dose administration of nebicapone affects the pharmacokinetics of warfarin.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Nebicapone plus warfarin BIA 3-202 BIA 3-202 200 mg tid + Warfarin 25 mg Warfarin warfarin Warfarin 25 mg Nebicapone plus warfarin warfarin BIA 3-202 200 mg tid + Warfarin 25 mg
- Primary Outcome Measures
Name Time Method Mean Cmax of S-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Maximum observed plasma drug concentration (Cmax)
Mean tmax of R-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Time of occurrence of Cmax (tmax)
Mean λz of R-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Apparent terminal rate constant calculated by log-linear regression of the terminal segment of the concentration versus time curve (λz)
Mean tmax of S-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Time of occurrence of Cmax (tmax)
Mean t1/2 of S-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Apparent terminal half-life, calculated from ln 2/λz (t1/2).
Mean Cmax of R-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Maximum observed plasma drug concentration (Cmax)
Mean AUC0-144 of R-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Area under the plasma concentration-time curve (AUC) from time zero to 144 h post-warfarin dose (AUC0-144), calculated by the linear trapezoidal rule
Mean AUC0-144 of S-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Area under the plasma concentration-time curve (AUC) from time zero to 144 h post-warfarin dose (AUC0-144), calculated by the linear trapezoidal rule
Mean λz of S-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Apparent terminal rate constant calculated by log-linear regression of the terminal segment of the concentration versus time curve (λz)
Mean t1/2 of R-warfarin before the warfarin dose, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hours post-warfarin dose Apparent terminal half-life, calculated from ln 2/λz (t1/2).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Human Pharmacology Unit (UFH),
🇵🇹S. Mamede do Coronado, Portugal