Food Effect and Dosage Form Proportionality Study of Eslicarbazepine Acetate

Food Effect and Dosage Form Proportionality Study of Eslicarbazepine Acetate Market Formulation in Healthy Volunteers

Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: BIA 2-093

Detailed Description

Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects. The study consisted of 3 periods separated by a washout of 7 days or more between doses. Subjects received a single oral 800 mg dose of eslicarbazepine acetate following a standard meal in one period, and following at least 10 hours of fasting in two periods.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged between 18 and 55 years, inclusive.
• Subjects of body mass index (BMI, kg/m2) within the normal range [4], i.e., between 18.50 and 24.99, inclusive.
• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead ECG.
• Subjects who had clinical laboratory test results clinically acceptable at screening and admission to first treatment period.
• Subjects who had negative tests for HBsAg, anti-HCVAb and anti- HIV-1 and HIV-2 Ab at screening.
• Subjects who had a negative screen for alcohol and drugs of abuse at screening.
• Subjects who were non-smokers or ex-smokers who discontinued smoking at least 3 months prior to admission.
• Subjects who were able and willing to give written informed consent.
• (If female) She was not of childbearing potential by reason of surgery (hysterectomy or tubal ligation) or, if of childbearing potential, she used one of the following methods of contraception: intrauterine device (by the study subject) + condom (by the partner), diaphragm (by the study subject) + condom (by the partner), or spermicide (by the study subject) + condom (by the partner).
• (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.

Exclusion Criteria:

• Subjects who did not conform to the above inclusion criteria, or
• 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 clinically relevant surgical history.
• Subjects who had a clinically relevant family history.
• 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 used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments.
• Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission.
• Subjects who had previously received eslicarbazepine acetate (ESL, BIA 2-093).
• Subjects who donated or received any blood or blood products within the previous 2 months prior to screening.
• Subjects who were vegetarians, vegans or have medical dietary restrictions.
• Subjects who could not 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 give written informed consent.
• (If female) She was pregnant or breast-feeding.
• (If female) She was of childbearing potential and she did not used and approved effective contraceptive method or she used oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIA 2-093 800 mg fasting; Tablets 800 mg. Administration:Oral.	Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate
Experimental: BIA 2-093 800 mg fed; Tablets 800 mg. Administration:Oral.	Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate
Experimental: BIA 2-093 400 mg; Tablets 2 x 400 mg. Administration:Oral.	Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (BIA 2-005)	Cmax (BIA 2-005) - maximum observed plasma drug concentration of BIA 2-005 (BIA 2-093 metabolite)	pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t (BIA 2-005)	AUC0-t (BIA 2-005) - the area under the plasma concentration-time curve from time zero to the last sampling time at which BIA 2-005 concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule (BIA 2-005 is a BIA 2-093 metabolite)	pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
Tmax (BIA 2-005)	tmax (BIA 2-005) - the time of occurrence of Cmax of BIA 2-005 (BIA 2-005 is a BIA 2-093 metabolite)	pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
AUC0-∞ (BIA 2-005)	AUC0-∞ (BIA 2-005) - the area under the plasma BIA 2-005 concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant; (BIA 2-005 is a BIA 2-093 metabolite)	pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: November 7, 2014
• First Submitted That Met QC Criteria: November 7, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• 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; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-117