The Effect of BIA 2-093 on the Steady-state Pharmacokinetic Profile of Phenytoin in Patients

The purpose of this study is determine the interaction of eslicarbazepine acetate (ESL, BIA 2-093) on the steadystate pharmacokinetics of phenytoin in patients and to evaluate the tolerability and safety of ESL administered concomitantly with phenytoin in patients.

Study Overview

• Status: Terminated
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Eslicarbazepine acetate; Drug: phenytoin; Drug: Placebo

Detailed Description

This study was planned as a single-dose, open label phase (Phase A) followed by a multiple-dose, double-blind, randomised, placebo-controlled, two-way crossover phase (Phase B) study in patients taking phenytoin. Phase B consisted of two 14-day treatment periods separated by a washout period of 10 to 15 days. Subjects continued their usual phenytoin scheme and received a single dose of ESL 1200 mg (Phase A) and either ESL (600 mg from Day 1 to 7 and 1200 mg from Day 8 to 14) or matching placebo once-daily for 14 days in each period.

The study was prematurely terminated due to impossibility of recruiting the planned number of patients. Only 4 patients were admitted and this was considered a too small sample size to allow a reliable assessment of the potential interaction between ESL and phenytoin. Therefore, no pharmacokinetic evaluation was performed.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Lisbon, Portugal, 1649-035
    • Neurology Department, Hospital of Santa Maria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged between 18 and 65 years, inclusive.
• Subjects who were on an established regimen of phenytoin monotherapy, which had been stable for at least 3 months.
• Subjects who had clinical laboratory tests acceptable to the Investigator.
• Subjects who were negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) and human immunodeficiency viruses (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 gave written informed consent.
• (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 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 any disease that may interfere with the pharmacokinetics or pharmacodynamics of the Investigational Products, or may affect its safety.
• Subjects who had a history of relevant drug hypersensitivity.
• Subjects who had a history of alcoholism or drug abuse in the last 2 years.
• Subjects who consumed more than 21 units of alcohol a week.
• Subjects who had one of the following findings on the electrocardiogram (ECG): sinus bradycardia, sinoatrial block, atrioventricular block of any degree.
• 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 any drugs (other than phenytoin) that may affect the pharmacokinetic profile of the investigational products within 2 weeks of first dosing.
• Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study.
• Subjects who had previously received ESL.
• Subjects who had donated and/or received any blood or blood products within the previous 3 months prior to screening.
• Subjects who were vegetarians, vegans and/or have medical dietary restrictions.
• Subjects who cannot communicate reliably with the investigator.
• Subjects who were unlikely to co-operate with the requirements of the study.
• Subjects who were unwilling or unable to gave written informed consent.
• (If female) She was pregnant or breast-feeding.
• (If female) She was of childbearing potential and she did not use an approved effective contraceptive method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablets	Drug: Placebo; Tablets containing matching placebo; Other Names: Placebo tablets
Experimental: Eslicarbazepine acetate; ESL 600 mg tablets	Drug: Eslicarbazepine acetate; Tablets containing ESL 600 mg; Other Names: BIA 2-093
Active Comparator: phenytoin; Hidantina® 100 mg tablets	Drug: phenytoin; Hidantina® tablets containing 100 mg of phenytoin; Other Names: Hidantina® 100 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events reported	Number of the adverse events reported	3 weeks

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (Actual): March 1, 2003
• Study Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 13, 2013
• First Posted (Estimate): June 17, 2013

Study Record Updates

• Last Update Posted (Estimate): February 27, 2014
• Last Update Submitted That Met QC Criteria: February 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Anticonvulsant, BIA 2-093
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Eslicarbazepine acetate; Phenytoin
• Other Study ID Numbers: BIA-2093-106