Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers

Phase 1

Completed

• Conditions: Epilepsy
• Interventions: Drug: BIA 2-093; Drug: Oxcarbazepine

• Registration Number: NCT01679002
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

To investigate the steady-state pharmacokinetics of once-daily and twice-daily regimens of BIA 2-093 and twice-daily regimen of Oxcarbazepine (Trileptal®) in healthy subjects and to assess the tolerability of such regimens in healthy subjects.

Detailed Description

Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of three 8-day treatment periods separated by washout periods of 10-15 days. On each of the treatment periods the volunteers received either a daily oral dose of BIA 2-093 900 mg once-daily (od), BIA 2-093 450 mg twice-daily (bid), or Oxcarbazepine (Trileptal®) 450 mg bid.

Study Timeline

• Study Start: 2003-10
• Primary Completion: 2003-12
• Study Completion: 2003-12
• Study First Submitted: 2012-08-31
• Study First Submitted QC: 2012-08-31
• Study First Posted: 2012-09-05
• Results First Submitted: 2014-11-28
• Results First Submitted QC: 2014-12-31
• Results First Posted: 2015-01-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Subjects were eligible for entry into the study if they fulfilled the following 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 clinically acceptable.
• Subjects who were negative for HBsAg, 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 first 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.
• If case of female subjects, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, who used one of the following methods of contraception: double-barrier, intrauterine device or abstinence.
• If case of female subjects, subjects who had a negative pregnancy test at screening and first 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, 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 atopy.
• Subjects who had a history of hypersensitivity to carbamazepine or oxcarbazepine or any other 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 had a significant infection or known inflammatory process on screening and/or first admission.
• Subjects who had acute gastrointestinal symptoms at the time of screening and/or first admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who had used prescription or over-the-counter medication within two weeks of first admission.
• Subjects who had used any investigational drug and/or participated in any clinical trial within four 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 4 months prior to screening.
• Subjects who were vegetarians, vegans and/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.
• In case of female subjects, subjects who were pregnant or breast-feeding.
• In case of female subjects, subjects who were of childbearing potential and did not use an approved effective contraceptive method or used oral contraceptives.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group C	BIA 2-093	oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid
Group A	BIA 2-093	BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 900 mg bid
Group B	BIA 2-093	BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 900 mg od
Group A	Oxcarbazepine	BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 900 mg bid
Group B	Oxcarbazepine	BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 900 mg od
Group C	Oxcarbazepine	oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Observed Plasma Drug Concentration	pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose	Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine

Secondary Outcome Measures

Name	Time	Method
AUC - Area Under the Plasma Concentration Versus Time Curve	pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose	AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine
Number of of Subjects Reporting at Least One Adverse Event	8 weeks	Number of of subjects reporting at least one adverse event.

Trial Locations

Locations (1)

BIAL - Portela & Cª S.A. - Human Pharmacology Unit (UFH); 🇵🇹 S. Mamede Do Coronado, Trofa, Portugal