Open-label Drug Interaction Study Between Eslicarbazepine Acetate and Phenytoin.

Phase 1

Completed

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

• Registration Number: NCT02283827
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

Single centre, open-label, multiple doses, two parallel study groups each receiving two formulations in a one-sequence design

Detailed Description

Single centre, open-label, multiple doses, two parallel study groups each receiving two formulations in a one-sequence design:

Group A: Pre-treatment with ESL, treatment with ESL and ascending doses of phenytoin (PHT) in last phases;

Group B: Pre-treatment with PHT, treatment with PHT and ascending doses of ESL in last phases

Study Timeline

• Study Start: 2007-01
• Primary Completion: 2007-03
• Study Completion: 2007-03
• Study First Submitted: 2014-11-03
• Study First Submitted QC: 2014-11-03
• Study First Posted: 2014-11-05
• Status Verified: 2014-12
• Results First Submitted: 2014-12-01
• Results First Submitted QC: 2014-12-17
• Last Update Submitted: 2014-12-17
• Results First Posted: 2014-12-18
• Last Update Posted: 2014-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 32

Inclusion Criteria

• Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer
• Non-black male aged of at least 18 years but not older than 45 years with a body mass index (BMI) greater than or equal to 19 and below 30 kg/m2
• Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance (laboratory tests are presented in section 6.1.1.3)
• Healthy according to the medical history, laboratory results and physical examination
• Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day, and an ex-smoker is defined as someone who completely stopped smoking for at least 12 months before day 1 of this study

Exclusion Criteria

• Significant history of hypersensitivity to phenytoin, eslicarbazepine, oxcarbazepine, carbamazepine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, including but not limited to cholecystectomy
• Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease
• Presence of significant heart disease or disorder according to ECG
• Presence or history of significant central nervous system disorder like convulsion or depression
• Hemoglobin count below 135 g/L (at screening)
• Use of valproic acid in the previous 7 days prior to Day 1 of the study.
• Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the previous 28 days before day 1 of this study
• Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids,phenytoin and rifampin), in the previous 28 days before Day 1 of this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B BIA 2-093 + Phenytoin (PHT)	BIA 2-093	Day 1 to 2: Pre-treatment 2: 100 mg PHT Day 3 to 8: Treatment 2: 300 mg PHT Day 9 to 10: Treatment 2 + Pre-treatment 1: 300 mg PHT + 600 mg ESL Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
Group A BIA 2-093 + Phenytoin (PHT)	BIA 2-093	Day 1 to 2: Pre-treatment 1: 600 mg ESL Day 3 to 8: Treatment 1: 1200 mg ESL Day 9 to 10: Treatment 1 + Pre-treatment 2: 1200 mg ESL+ 100 mg PHT Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
Group A BIA 2-093 + Phenytoin (PHT)	Phenytoin	Day 1 to 2: Pre-treatment 1: 600 mg ESL Day 3 to 8: Treatment 1: 1200 mg ESL Day 9 to 10: Treatment 1 + Pre-treatment 2: 1200 mg ESL+ 100 mg PHT Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
Group B BIA 2-093 + Phenytoin (PHT)	Phenytoin	Day 1 to 2: Pre-treatment 2: 100 mg PHT Day 3 to 8: Treatment 2: 300 mg PHT Day 9 to 10: Treatment 2 + Pre-treatment 1: 300 mg PHT + 600 mg ESL Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT

Primary Outcome Measures

Name	Time	Method
Cmax - the Maximum Plasma Concentration	Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration	BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate

Secondary Outcome Measures

Name	Time	Method
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time	Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration	AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time; BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate
Tmax - the Time of Occurrence of Cmax	Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration	BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate