Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin

Healthy Clinical Trial

Official title:

Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02779348
• Other study ID #: BIA-3202-112
• Status: Completed
• Phase: Phase 1
• First received: May 18, 2016
• Last updated: August 23, 2017
• Start date: September 2006
• Est. completion date: December 2006

Study information

• Verified date: August 2017
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether multiple-dose administration of nebicapone affects the pharmacokinetics of warfarin.

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 2006
• Est. primary completion date: December 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BIA 3-202
Nebicapone tablets 200 mg
• warfarin
Varfine® 5 mg (warfarin 5 mg) tablets

Locations

Country	Name	City	State
Portugal	Human Pharmacology Unit (UFH),	S. Mamede do Coronado

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Cmax of S-warfarin	Maximum observed plasma drug concentration (Cmax)	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
Primary	Mean tmax of S-warfarin	Time of occurrence of Cmax (tmax)	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
Primary	Mean AUC0-144 of S-warfarin	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	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
Primary	Mean ?z of S-warfarin	Apparent terminal rate constant calculated by log-linear regression of the terminal segment of the concentration versus time curve (?z)	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
Primary	Mean t1/2 of S-warfarin	Apparent terminal half-life, calculated from ln 2/?z (t1/2).	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
Primary	Mean Cmax of R-warfarin	Maximum observed plasma drug concentration (Cmax)	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
Primary	Mean tmax of R-warfarin	Time of occurrence of Cmax (tmax)	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
Primary	Mean AUC0-144 of R-warfarin	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	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
Primary	Mean ?z of R-warfarin	Apparent terminal rate constant calculated by log-linear regression of the terminal segment of the concentration versus time curve (?z)	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
Primary	Mean t1/2 of R-warfarin	Apparent terminal half-life, calculated from ln 2/?z (t1/2).	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