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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02779348
Recruitment Status : Completed
First Posted : May 20, 2016
Last Update Posted : August 24, 2017
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.

Tracking Information
First Submitted Date  ICMJE May 18, 2016
First Posted Date  ICMJE May 20, 2016
Last Update Posted Date August 24, 2017
Study Start Date  ICMJE September 2006
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2016)
  • 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)
  • 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)
  • 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
  • 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)
  • 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).
  • 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)
  • 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)
  • 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
  • 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)
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin
Official Title  ICMJE Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: BIA 3-202
    Nebicapone tablets 200 mg
    Other Name: Nebicapone
  • Drug: warfarin
    Varfine® 5 mg (warfarin 5 mg) tablets
Study Arms  ICMJE
  • Experimental: Nebicapone plus warfarin
    BIA 3-202 200 mg tid + Warfarin 25 mg
    Interventions:
    • Drug: BIA 3-202
    • Drug: warfarin
  • Experimental: Warfarin
    Warfarin 25 mg
    Intervention: Drug: warfarin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2016)
16
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2006
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Portugal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02779348
Other Study ID Numbers  ICMJE BIA-3202-112
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Bial - Portela C S.A.
Study Sponsor  ICMJE Bial - Portela C S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bial - Portela C S.A.
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP