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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease (PD)
• Intervention / Treatment: Drug: BIA 9-1067; Drug: Warfarin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Trofa
    • S. Mamede do Coronado, Trofa, Portugal, 4745-457
      • BIAL - Portela & Cª - Human Pharmacology Unit (UFH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Period 1: BIA 9-1067 + warfarin Period 2: warfarin	Drug: BIA 9-1067; BIA 9-1067 25 mg; Other Names: OPC, Opicapone; Drug: Warfarin; Warfarin 25 mg; Other Names: Varfine®
Active Comparator: Group 2; Period 1: warfarin Period 2: BIA 9-1067 + warfarin	Drug: BIA 9-1067; BIA 9-1067 25 mg; Other Names: OPC, Opicapone; Drug: Warfarin; Warfarin 25 mg; Other Names: Varfine®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: January 24, 2012
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Estimate): December 22, 2015
• Last Update Submitted That Met QC Criteria: November 18, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's disease (PD); Opicapone; BIA 9-1067
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anticoagulants; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Warfarin; Opicapone
• Other Study ID Numbers: BIA-91067-116