A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic Profile and CNS Effects of BIA 2-093

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and tolerability of multiple dose regimens of BIA 2-093 in healthy young male volunteers

Detailed Description
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Single centre, Phase I, double-blind, randomised, placebo-controlled study investigating 4 multiple rising oral doses of BIA 2-093 in 4 groups of 8 young healthy male subjects. Within each group, 2 subjects were randomised to receive placebo and the remaining 6 subjects to receive BIA 2-093. No subject was a member of more than one group. The dose regimens investigated were: 200 mg b.i.d.(twice daily), 400 mg o.d.(once daily; this was changed from 400 mg b.i.d. in protocol amendment 1, on the basis of interim pharmacokinetic analysis of Group 1 data), 800 mg o.d, and 1200 mg o.d. BIA 2-093/placebo was administered orally once daily on Days 1-8, or twice a day (at 12-hour intervals) on Days 1-7 with a final dose in the morning of Day 8. The multiple dose regimens were to be investigated in ascending order. Progression to each higher dose level was only to occur if the previous dose level was deemed by the investigator and the sponsor to be safe and well tolerated.

Official Title
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A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic Profile and CNS Effects of BIA 2-093, in Young Healthy Male Volunteers.

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Placebo
* Drug: BIA 2-093


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males aged 18-45 years, with a body mass index (BMI) of 19-28 kg/m2. Subjects who were healthy as determined by pre-study medical history, physical examination, 12-lead ECG and EEG. Subjects who had clinical laboratory tests acceptable to the investigator. Subjects who were negative for HbsAg, anti-HCV and HIV I and II tests at screening. Subjects who were negative for drugs of abuse and alcohol tests at screening and admission. Subjects who were non-smokers or previous smokers who had not smoked for at least 6 months. Subjects who were able and willing to give written informed consent. 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 (carbamazepine and related compounds). Subjects who had a history of alcoholism. Subjects who had a history of drug abuse. Subjects who consumed more than 28 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 an acute infection such as influenza at the time of screening and/or admission. Subjects who had used prescription drugs within 4 weeks of first dosing. Subjects who had used over the counter medication, excluding routine vitamins but including mega dose vitamin therapy, within one week of dosing. Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of admission to this study. Subjects who had donated and/or received any blood or blood products within 3 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. Subjects who had previously received BIA 2-093.

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

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1- 200 mg b.i.d. (twice daily)<br>BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets. | Drug: Placebo<br> <br> * Other names: PLC, Placebo;Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|
| Experimental: Group 2 - 400 mg b.i.d.<br>BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets. | Drug: Placebo<br> <br> * Other names: PLC, Placebo;Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|
| Experimental: Group 3- 800 mg o.d. (once daily)<br>BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets. | Drug: Placebo<br> <br> * Other names: PLC, Placebo;Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|
| Experimental: Group 4 - either 800 mg b.i.d or 1200 mg o.d.<br>BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets. | Drug: Placebo<br> <br> * Other names: PLC, Placebo;Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Adverse Events | Total Number of Adverse Events. | up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax - Maximum observed plasma concentration | Day 1 and Day 8 | 
| AUC0-τ | AUC0-τ - Area under the plasma concentration time curve to last measurable time point Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose | Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose | 

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