Effect of BIA 9-1067 on the Pharmacokinetics and Pharmacodynamics of Warfarin

Parkinson's Disease (PD) Clinical Trial

Official title:

Effect of BIA 9-1067 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02169440
• Other study ID #: BIA-91067-116
• Status: Completed
• Phase: Phase 1
• First received: January 24, 2012
• Last updated: November 18, 2015
• Start date: June 2009
• Est. completion date: July 2009

Study information

• Verified date: November 2015
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: INFARMED, National Authority of Medicines and Health Products, IP
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate CYP2C9 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of S-warfarin, a substrate of CYP2C9.

Description:

Single-centre, open-label, randomised, two-way crossover study in healthy young male and female volunteers. The study was to consist of 2 treatment periods separated by a washout period of 14 days or more. In one period, subjects were to receive a single-dose of 25 mg BIA 9-1067 with a single-dose of racemic 25 mg warfarin. In the other period, a 25 mg warfarin single-dose was to be administered alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Able and willing to give written informed consent.

• 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.

• Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.

• Clinical laboratory test results clinically acceptable at screening and admission to each treatment period.

• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.

• Non-smokers or ex-smokers for at least 3 months.

• (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 or intrauterine device.

• (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.

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 have affected the safety or other study assessments, in the investigator's opinion.

• Had previously received BIA 9-1067.

• 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.

• Employees at BIAL - Portela & Co, SA.

• (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 or intra-uterine device) or she used oral contraceptives.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease (PD)

Intervention

Drug:
• BIA 9-1067
BIA 9-1067 25 mg
• Warfarin
Warfarin 25 mg

Locations

Country	Name	City	State
Portugal	BIAL - Portela & Cª - Human Pharmacology Unit (UFH)	S. Mamede do Coronado	Trofa

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	Cmax - Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)	Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	Tmax - Time to Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)	Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (BIA 9-1067 + Warfarin)	Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	Cmax = Maximum Plasma Concentration (Warfarin Alone)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	Tmax - Time to Maximum Observed Plasma Concentration (Warfarin Alone)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin Alone)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	Cmax - Maximum Observed Plasma Concentration (Warfarin + BIA 9-1067)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	Tmax - Time to Maximum Observed Plasma Concentration (Warfarin + BIA 9-1067)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No
Primary	AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin + BIA 9-1067)	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	No