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

Study Overview
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Brief Summary
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Single centre, open-label, randomised study in four parallel groups of healthy volunteers

Detailed Description
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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.

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

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093
* Drug: S-licarbazepine
* Drug: R-licarbazepine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - the Maximum Plasma Concentration |  | 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 |  | 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 |  | 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 |  | 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. |