Disposition of Eslicarbazepine Acetate and Its Metabolites S-licarbazepine and R-licarbazepine

Disposition of Eslicarbazepine Acetate and Its Metabolites S-licarbazepine and R-licarbazepine Following Oral Administration in Healthy Volunteers

Single centre, open-label, randomised study in four parallel groups of healthy volunteers

Study Overview

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

Detailed Description

Single centre, open-label, randomised study in four parallel groups of healthy volunteers: Group 1 = 900 mg of eslicarbazepine acetate (ESL, BIA 2-093); Group 2 = 450 mg of S-licarbazepine plus 450 mg of R-licarbazepine; Group 3 = 450 mg of S-licarbazepine; Group 4 = 450 mg of Rlicarbazepine. In each group, the study consisted of a single-dose period (Phase A) followed by a repeateddose period of 7 days of duration in which the investigational product was administered once daily (Phase B). The repeated-dose phase started 96 h post single-dose.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, D-22525
    • Scope International Life Sciences AG,

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Male or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, neurological examination, and 12-lead ECG.
• Subjects who had clinical laboratory tests clinically acceptable at screening and admission.
• Subjects who had negative tests for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab at screening.
• Subjects who were negative for drugs of abuse and alcohol at screening and admission.
• Subjects who were non-smokers or who smoke < 10 cigarettes or equivalent per day.
• Subjects who are able and willing to give written informed consent.
• (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier, intrauterine device or abstinence.
• (If female) She had a negative pregnancy test at screening and admission to Phase A.

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 atopy.
• Subjects who had a history of relevant drug hypersensitivity (especially carbamazepine or oxcarbazepine).
• 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 or admission.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eslicarbazepine acetate; 900mg of eslicarbazepine acetate (ESL, BIA 2-093)	Drug: BIA 2-093; Tablets containing 900 mg
Active Comparator: S-licarbazepine R-licarbazepine; 450 mg of S-licarbazepine plus 450 mg of R-licarbazepine	Drug: S-licarbazepine; capsules containing 225 mg; Drug: R-licarbazepine; capsules containing 225 mg
Active Comparator: S-licarbazepine; 450 mg of S-licarbazepine	Drug: S-licarbazepine; capsules containing 225 mg
Active Comparator: R-licarbazepine; 450 mg of Rlicarbazepine	Drug: R-licarbazepine; capsules containing 225 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - the Maximum Plasma Concentration	BIA 2-194, BIA 2-195 and Oxcarbazepine are metabolites of BIA 2-093 and Licarbazepine.	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
Tmax - the Time of Occurrence of Cmax	BIA 2-194, BIA 2-195 and Oxcarbazepine are metabolites of BIA 2-093 and Licarbazepine.	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity	BIA 2-194, BIA 2-195 and Oxcarbazepine are metabolites of BIA 2-093 and Licarbazepine.	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t - the Area Under the Plasma Concentration-time Curve to Last Measurable Time Point	BIA 2-194, BIA 2-195 and Oxcarbazepine are metabolites of BIA 2-093 and Licarbazepine.	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimated): November 2, 2014

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

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; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Anticonvulsants; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-115

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No