Healthy
Conditions
Keywords
Nebicapone, Warfarin
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.
Interventions
DRUGBIA 3-202
Nebicapone tablets 200 mg
DRUGwarfarin
Varfine® 5 mg (warfarin 5 mg) tablets
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 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). |
Countries
Portugal
Outcome results
None listed