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Completed

NCT Number: NCT02779348

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.

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Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Human Pharmacology Unit (UFH),

S. Mamede Do Coronado, 4745-457, Portugal

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BIA 3-202

Drug

Nebicapone tablets 200 mg

Other names: Nebicapone

Warfarin

Drug

Varfine® 5 mg (warfarin 5 mg) tablets

Primary outcomes

  1. Mean Cmax of S-warfarin

    Time frame: 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)

  2. Mean tmax of S-warfarin

    Time frame: 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)

  3. Mean AUC0-144 of S-warfarin

    Time frame: 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

  4. Mean λz of S-warfarin

    Time frame: 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)

  5. Mean t1/2 of S-warfarin

    Time frame: 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).

  6. Mean Cmax of R-warfarin

    Time frame: 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)

  7. Mean tmax of R-warfarin

    Time frame: 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)

  8. Mean AUC0-144 of R-warfarin

    Time frame: 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

  9. Mean λz of R-warfarin

    Time frame: 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)

  10. Mean t1/2 of R-warfarin

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Bial - Portela C S.A.

Industry

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2006
Study completion
2006
First posted
May 20, 2016
Registry last updated
Aug 24, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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