Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of age on the pharmacokinetic profile of BIA 2-093 and its active metabolites.

Detailed Description
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This was a single-centre, open-label, parallel group, non-randomised study with a single-dose phase (Phase A) followed by a multiple-dose phase (Phase B), in 12 healthy elderly and 12 healthy young subjects. During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.

Official Title
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Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites in Healthy Elderly Subjects Compared With Those in Healthy Young Subjects

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged between 18 and 40 years, inclusive OR male or female subjects aged 65 years or more. If young, subjects who were within 15% of ideal body weight OR, if elderly, subjects who were within 20% of ideal body weight according to the Metropolitan Life Insurance Table. 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 to the Investigator. Subjects who were negative for HBsAg, HCVAb and HIV-1 and HIV-2 Ab tests at screening. Subjects who were negative for alcohol and drugs of abuse at screening. 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 female) She was not of childbearing potential by reason of surgery or menopause or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine. (If female and with less than 40 years old) She had a negative pregnancy test at screening. 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 14 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 drugs within 2 weeks of first dosing. Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study. 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. (If female) She was pregnant or breast-feeding (If female) She was of childbearing potential and she did not use an authorised effective contraceptive method.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elderly subjects<br>14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. | Drug: BIA 2-093<br>* During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.<br>* Other names: Eslicarbazepine acetate;|
| Experimental: Young subjects<br>16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. | Drug: BIA 2-093<br>* During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.<br>* Other names: Eslicarbazepine acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Drug Concentration (Cmax) | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax - Time of Maximum Observed Concentration | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | 
| AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eslicarbazepine acetate, BIA 2-093