The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin

Phase 1

Completed

• Conditions: Epilepsy
• Interventions: Drug: BIA 2-093; Drug: Warfarin

• Registration Number: NCT02287415
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

Multiple-dose, open-label, single-period study consisting of three consecutive phases

Detailed Description

Multiple-dose, open-label, single-period study consisting of three consecutive phases: Phase A - run-in warfarin dose-finding phase Phase B - warfarin pharmacokinetics (PK) and international normalised ratio (INR) profiling Phase C - warfarin alone at their individualised doses

Study Timeline

• Study Start: 2002-05
• Primary Completion: 2002-07
• Study Completion: 2002-07
• Status Verified: 2014-11
• Study First Submitted: 2014-11-06
• Study First Submitted QC: 2014-11-07
• Study First Posted: 2014-11-10
• Results First Submitted: 2014-11-28
• Results First Submitted QC: 2014-11-28
• Last Update Submitted: 2014-11-28
• Results First Posted: 2014-12-01
• Last Update Posted: 2014-12-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Male or female subjects aged between 18 and 45 years, inclusive
• Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive
• Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG
• Subjects who had clinical laboratory tests clinically acceptable
• Subjects who were negative for HBs Ag, anti-HCV Ab and anti-HIV-1 and HIV-2 Ab tests at screening
• Subjects who were negative for alcohol and drugs of abuse at screening
• Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day
• Subjects who were able and willing to give written informed consent
• In case of female volunteers, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, used one of the following methods of contraception: double-barrier or intrauterine device
• In case of female volunteers, subjects who had a negative pregnancy test at screening

Exclusion Criteria

• Subjects who did not conform to the above inclusion criteria
• Subjects who had a 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
• Subjects who had a current haemostatic disorder or a personal or family history of any such disorder
• Subjects who had a personal or family history of bleeding complications after surgery or tooth extraction, nose or gingival bleeding, or haemorrhagic diathesis.
• Subjects with a profession or activities implying a special risk of trauma
• Subjects with any abnormality in the coagulation status (aPTT or prothrombin INR)
• Subjects who had a clinically relevant surgical history
• Subjects who had a clinically relevant family history
• Subjects who had a history of relevant atopy
• Subjects who had a history of relevant drug hypersensitivity
• Subjects who had a history of alcoholism or drug abuse
• Subjects who consumed more than 14 units of alcohol a week
• Subjects who had a significant infection or known inflammatory process on screening and/or admission
• Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn)
• Subjects who had used prescription drugs within 2 weeks prior admission on Phase A
• Subjects who had used any investigational drug and/or participated in any clinical trial within 2 months prior admission to Phase A
• Subjects who had previously received BIA 2-093
• Subjects who had donated and/or received any blood or blood products within the previous 2 months prior admission to Phase A
• Subjects who were vegetarians, vegans and/or had medical dietary restrictions
• Subjects who could not communicate reliably with the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 1	BIA 2-093	Phase A: Warfarin Phase B: Warfarin + BIA 2-093 (ESL) Phase C: Warfarin
Group 1	Warfarin	Phase A: Warfarin Phase B: Warfarin + BIA 2-093 (ESL) Phase C: Warfarin

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Steady-state Plasma Concentration	PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.

Secondary Outcome Measures

Name	Time	Method
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval	PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
Tmax - Time of Occurrence of Cmax	PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.