Tolerability and Pharmacokinetics of a Single 900 mg Oral Dose of BIA 2-093 and Oxcarbazepine in Healthy Volunteers

To investigate the pharmacokinetics of a single 900 mg oral dose of BIA 2-093 and a single 900 mg oral dose of Oxcarbazepine in healthy volunteers and to assess the tolerability of a single 900 mg dose of BIA 2-093 and Oxcarbazepine.

Study Overview

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

Detailed Description

Single centre, open label, balanced randomised, two-way crossover study in 12 healthy volunteers. The study consisted of 2 periods separated by a washout period of 7 days or more. On each of the study periods the volunteers received either a single 900 mg oral dose of BIA 2-093 or a single 900 mg oral dose of Oxcarbazepine.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Trofa
    • S. Mamede do Coronado, Trofa, Portugal, 4745-457
      • BIAL - Portela & Cª - Human Pharmacology Unit (UFH)

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 or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.
• Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG.
• Subjects who had clinical laboratory tests acceptable.
• Subjects who were negative for HBs Ag, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening.
• Subjects who were negative for alcohol and drugs of abuse at screening and admission.
• Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day.
• Subjects who were able and willing to give written informed consent.
• In case of female volunteers, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, used one of the following methods of contraception: double-barrier, intrauterine device or abstinence.
• In case of female volunteers, subjects who had a negative pregnancy test at screening and admission

Exclusion Criteria:

• Subjects who did not conform to the above inclusion criteria.
• Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, 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 atopy.
• Subjects who had a history of relevant drug hypersensitivity.
• Subjects who had a history of alcoholism or drug abuse.
• Subjects who consumed more than 21 units of alcohol a week.
• 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 prescription drugs within 4 weeks of first dosing.
• Subjects who had used over-the-counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing.
• Subjects who had used any investigational drug and/or participated in any clinical trial within 2 months of their first admission.
• Subjects who had previously received BIA 2-093.
• Subjects who had donated and/or received any blood or blood products within the previous 2 months prior to screening.
• Subjects who were vegetarians, vegans and/or had 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.
• In case of female volunteers, subjects who were pregnant or breast-feeding.
• In case of female volunteers, subjects who were of childbearing potential and did not use an approved effective contraceptive method or used oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1 BIA 2-093 + Oxcarbazepine; Period 1 - Subjects recieved 900 mg of BIA 2-093 Period 2 - Subjects recieved 900 mg of oxcarbazepine	Drug: BIA 2-093; Tablets containing BIA 2-093 in doses of 300 and 600 mg; Other Names: Eslicarbazepine acetate; Drug: Oxcarbazepine; Tablets containing 300 mg and 600 mg of Trileptal®; Other Names: Trileptal®
ACTIVE_COMPARATOR: Group 2 Oxcarbazepine + BIA 2-093; Period 1 - Subjects recieved 900 mg of oxcarbazepine Period 2 - Subjects recieved 900 mg of BIA 2-093	Drug: BIA 2-093; Tablets containing BIA 2-093 in doses of 300 and 600 mg; Other Names: Eslicarbazepine acetate; Drug: Oxcarbazepine; Tablets containing 300 mg and 600 mg of Trileptal®; Other Names: Trileptal®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Drug Concentration (Cmax)	Maximum observed plasma concentration (Cmax) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine.	at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve (AUC)	Area under the plasma concentration versus time curve (AUC) to last measurable time point (AUC0-t) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine.	at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total of Subjects Reporting at Least One Adverse Event	Monitoring of Adverse Events throughout the study: Safety was evaluated from the number of reported adverse events (AEs) by patient	4 weeks

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (ACTUAL): April 1, 2002
• Study Completion (ACTUAL): April 1, 2002

Study Registration Dates

• First Submitted: August 31, 2012
• First Submitted That Met QC Criteria: September 4, 2012
• First Posted (ESTIMATE): September 5, 2012

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

• Keywords: Epilepsy; Eslicarbazepine acetate; Oxcarbazepine
• 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 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Eslicarbazepine acetate; Oxcarbazepine
• Other Study ID Numbers: BIA-2093-104