Clinical trial NCT02779348: Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin
Official title: Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Nebicapone
Warfarin
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2016-05-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Cmax of S-warfarin
timeFrame: 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
measure: Mean tmax of S-warfarin
timeFrame: 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
measure: Mean AUC0-144 of S-warfarin
timeFrame: 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
measure: Mean λz of S-warfarin
timeFrame: 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
measure: Mean t1/2 of S-warfarin
timeFrame: 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
measure: Mean Cmax of R-warfarin
timeFrame: 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
measure: Mean tmax of R-warfarin
timeFrame: 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
measure: Mean AUC0-144 of R-warfarin
timeFrame: 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
measure: Mean λz of R-warfarin
timeFrame: 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
measure: Mean t1/2 of R-warfarin
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: S. Mamede do Coronado
country: Portugal
facility: Human Pharmacology Unit (UFH),
Study officials:
References: