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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02169440

Enrollment

Registered

2014-06-23

Start date

2009-06-30

Completion date

2009-07-31

Last updated

2015-12-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson's Disease (PD)

Keywords

Parkinson's disease (PD), BIA 9-1067, Opicapone

Brief 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.

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.

Interventions

DRUGBIA 9-1067

BIA 9-1067 25 mg

DRUGWarfarin

Warfarin 25 mg

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Cmax - Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	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
Tmax - Time to Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	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
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (BIA 9-1067 + Warfarin)	before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.	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
Cmax = Maximum Plasma Concentration (Warfarin 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
Tmax - Time to Maximum Observed Plasma Concentration (Warfarin 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
Cmax - Maximum Observed Plasma Concentration (Warfarin + 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
Tmax - Time to Maximum Observed Plasma Concentration (Warfarin + 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin + 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.	Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067

Countries

Portugal

Participant flow

Participants by arm

Arm	Count
Group 1: BIA 9-1067 + Warfarin, Then Warfarin Period 1: BIA 9-1067 + warfarin Period 2: warfarin BIA 9-1067: BIA 9-1067 25 mg Warfarin: Warfarin 25 mg	10
Group 2: Warfarin, Then BIA 9-1067 + Warfarin Period 1: warfarin Period 2: BIA 9-1067 + warfarin BIA 9-1067: BIA 9-1067 25 mg Warfarin: Warfarin 25 mg	10
Total	20

Baseline characteristics

Characteristic	Group 1: BIA 9-1067 + Warfarin, Then Warfarin	Group 2: Warfarin, Then BIA 9-1067 + Warfarin	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	10 Participants	10 Participants	20 Participants
Sex: Female, Male Female	5 Participants	5 Participants	10 Participants
Sex: Female, Male Male	5 Participants	5 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 20	7 / 20
serious Total, serious adverse events	0 / 20	0 / 20

Outcome results

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