Pharmacokinetic Interaction Study Between Eslicarbazepine Acetate and Carbamazepine

Pharmacokinetic Interaction Study Between Eslicarbazepine Acetate and Carbamazepine in Healthy Subject

Open-label study in two parallel groups of 20 healthy subjects each. Group A assessed the effect of CBZ on ESL pharmacokinetics, and Group B assessed the effect of ESL on CBZ pharmacokinetics.

Study Overview

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

Detailed Description

Open-label study in two parallel groups of 20 healthy subjects each. Group A assessed the effect of CBZ on ESL pharmacokinetics, and Group B assessed the effect of ESL on CBZ pharmacokinetics. Each patient participated in the study for approximately 9 weeks. The clinical portion of the study was completed in approximately 3 months. Subjects received the treatments during 35 days.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects aged 18 to 45 years inclusive;
• Body mass index (BMI) between 18 and 30 kg/m2 inclusive;
• Healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG); negative tests for Hepatitis B surface Antigen (HBsAg), anti-HCVAb and Human Immunodeficiency Virus (HIV)-1 and HIV-2 Ab at screening;
• Clinical laboratory test results clinically acceptable at screening and admission to each treatment period;
• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period;
• Non-smokers or ex-smokers;
• Able and willing to give written informed consent;
• If female, not of childbearing potential by reason of surgery or, if of childbearing potential, she used a double-barrier method of contraception: 1 male barrier method [male condom] plus 1 female barrier method (diaphragm, spermicide, or intrauterine device);
• If female, had a negative urine pregnancy test at screening and admission to each treatment period.

Exclusion Criteria:

• 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; have a clinically relevant surgical history;
• History of relevant atopy or any drug hypersensitivity (including known hypersensitivity to ESL or other carboxamide derivatives [e.g., carbamazepine, oxcarbazepine] or any of its excipients; known hypersensitivity to drugs structurally related to carbamazepine [e.g.: tricyclic antidepressants] or any of its excipients);
• Second or third-degree atrioventricular blockade not corrected with a pace-maker or any other clinically significant abnormality in the 12-lead ECG as determined by the investigator;
• History of alcoholism or drug abuse;
• Consumed more than 14 units1 of alcohol a week;
• Significant infection or known inflammatory process on screening or admission to each treatment period;
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;
• Use of medicines within two weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion;
• Had donated or received any blood or blood products within the 3 months prior to screening;
• Vegetarians, vegans or have other medical dietary restrictions;
• Could not communicate reliably with the investigator; was unlikely to co-operate with the requirements of the study;
• Unwilling or unable to give written informed consent;
• If female, was pregnant or breast-feeding;
• If female, was of childbearing potential and did not use an accepted effective contraceptive method or used hormonal contraceptives;
• Had received an investigational drug within 3 months of screening or was currently participating in another study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Day 1 to Day 8 - BIA 2-093 800 mg Day 9 to Day 14 - BIA 2-093 800 mg + CBZ 200 mg Day 15 to Day 22 - BIA 2-093 800 mg + CBZ 400 mg Day 23 to Day 35 - BIA 2-093 800 mg + CBZ 400 mg twice-daily	Drug: BIA 2-093; Other Names: Eslicarbazepine acetate; ESL; Drug: Carbamazepine; Other Names: CBZ
Experimental: Group B; Day 1 to Day 8 - CBZ 200 mg Day 9 to Day 14 - CBZ 400 mg Day 15 to Day 29 - CBZ 400 mg twice-daily Day 30 to Day 35 - BIA 2-093 800 mg + CBZ 400 mg twice-daily	Drug: BIA 2-093; Other Names: Eslicarbazepine acetate; ESL; Drug: Carbamazepine; Other Names: CBZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (BIA 2-093) - the Maximum Plasma Concentration	Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg	Day 7 to 35
Cmax (CBZ) - the Maximum Plasma Concentration	Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg	Day 28 to 35
Cmax (CBZE) - the Maximum Plasma Concentration	Reference - Day 28 following twice-daily oral administration of CBZ 400 mg twice-daily Test - Day 35 following twice-daily oral administration of CBZ 400 mg twice-daily CBZE - carbamazepine-epoxide is the active metabolite of CBZ	Day 28 to 35
AUC0-t (BIA 2-093) - Area Under the Curve to Last Measurable Concentration for BIA 2-093	Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg	Day 7 to 35
AUC0-t (CBZ) - Area Under the Curve to Last Measurable Concentration for CBZ	Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg	Day 28 to 35
AUC0-t (CBZE) - Area Under the Curve to Last Measurable Concentration for CBZE	Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg CBZE - carbamazepine-epoxide is the active metabolite of CBZ	Day 28 to 35

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 6, 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Eslicarbazepine acetate; Carbamazepine
• Other Study ID Numbers: BIA-2093-129