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

NCT02169440 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-116
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease (PD)

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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.

Study Arms (2)

Group 1

EXPERIMENTAL

Period 1: BIA 9-1067 + warfarin Period 2: warfarin

Drug: BIA 9-1067; Drug: Warfarin

Group 2

ACTIVE COMPARATOR

Period 1: warfarin Period 2: BIA 9-1067 + warfarin

Drug: BIA 9-1067; Drug: Warfarin

Interventions

BIA 9-1067 DRUG

BIA 9-1067 25 mg

Also known as: OPC, Opicapone

Group 1; Group 2

Warfarin DRUG

Warfarin 25 mg

Also known as: Varfine®

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

BIAL - Portela & Cª - Human Pharmacology Unit (UFH)

S. Mamede Do Coronado, Trofa, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

opicapone; Warfarin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Head of Clinical Research
• Organization: Bial - Portela & Cª, S.A.

jose.rocha@bial.com

+351 229 866 100

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: June 23, 2014
• Study Start: June 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: December 22, 2015
• Results First Posted: December 22, 2015

Record last verified: 2015-11

Locations

PT (1)