Comparative Bioavailability Study of Two Different Sources of Eslicarbazepine Acetate

Comparative Bioavailability Study of Two Different Sources of Eslicarbazepine Acetate in Healthy Subjects

Phase I, two-centre, open-label, randomized, gender-balanced, single-dose, laboratory blinded, two-period, two-sequence, crossover study in 2 groups of 20 healthy male and female subjects, to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL)

Study Overview

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

Detailed Description

Phase I, two-centre, open-label, randomized, gender-balanced, single-dose, laboratory blinded, two-period, two-sequence, crossover study in 2 groups of 20 healthy male and female subjects. The study consisted in 2 periods separated by a wash-out of at least 7 days between doses. To demonstrate the bioequivalence (BE) between two active product ingredient (API) sources [current API source - marketed formulation (MF) versus new API source - to-be-marketed (TBM)] of eslicarbazepine acetate (ESL)

• Study Type: Interventional
• Enrollment (Actual): 40
• 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:

• A signed and dated informed consent form before any study-specific screening procedure was performed,
• Healthy male or female 18 to 55 of age, inclusive,
• Had a BMI within the range of 18 to 25 kg/m2 inclusive at screening,
• Had a physical examination, vital signs, electrocardiogram (ECG) and routine laboratory tests within normal ranges or considered as non clinically significant (NCS) by the Investigator,
• Non-smokers or smokers of less than 10 cigarettes per day,
• If female, she was not of childbearing potential by reason of surgery (hysterectomy, bilateral oophorectomy or tubal ligation) or, if of childbearing potential, she had to be using one of the following effective method of contraception (intrauterine device (IUD) or abstention or condom) for the duration of the trial and had to have a negative urine pregnancy test at screening visit and upon each admission period.

Exclusion Criteria:

• Had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders, or have a clinically relevant surgical history,
• Presented any disease or condition (medical or surgical) which, in the opinion of the Investigator, that may have interfered with the absorption, distribution, metabolism or excretion of study drug,
• Had a history of relevant atopy or any drug hypersensitivity (including known hypersensitivity to eslicarbazepine acetate or any of its excipients),
• Had a history of alcoholism or drug abuse within 1 year before D 1,
• Consumption of more than 50 g of ethanol per day (12.5 Centiliters [cL] glass of 10° [10%] wine = 12 g; 4 cL of aperitif, 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g),
• Use of medicines within 2 weeks of admission to first treatment period that could affect, in the Investigator's opinion, the safety of the subject,
• Had used any investigational drug or participated in any clinical trial within 2 months of admission to first treatment period,
• Had donated or received any blood or blood products within 2 months prior to screening,
• Could not communicate reliably with the investigator, was unlikely to co-operate with the requirements of the study,
• Was unwilling or unable to give written informed consent,
• If female, was pregnant or breast-feeding,

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 BIA 2-093; Subjects randomly received on period 1 and 2, either a single 400 mg tablet of ESL (MF - marketed formulation), or a single 400 mg tablet of ESL (TBM - o-be-marketed);	Drug: BIA 2-093; MF - Marketed formulation; Other Names: ESL, Eslicarbazepine acetate; Drug: BIA 2-093; TBM - to-be-marketed; Other Names: ESL, Eslicarbazepine acetate
Experimental: Group 2 BIA 2-093; Subjects randomly received on period 1 and 2, either a single 800 mg tablet of ESL (MF - marketed formulation), or a single 800 mg dose of ESL (TBM - o-be-marketed).	Drug: BIA 2-093; MF - Marketed formulation; Other Names: ESL, Eslicarbazepine acetate; Drug: BIA 2-093; TBM - to-be-marketed; Other Names: ESL, Eslicarbazepine acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Plasma Concentration	Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite	pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
Tmax - Time of Occurrence of Cmax	Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite	pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification	Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite	pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 5, 2014
• First Posted (Estimate): November 6, 2014

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

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-2093-130