Epilepsy
Conditions
Keywords
Epilepsy, BIA 2-093, Eslicarbazepine acetate
Brief summary
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
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.
Interventions
DRUGPlacebo
DRUGBIA 2-093
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Adverse Events | up to 20 weeks | Total Number of Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Day 1 and Day 8 | Cmax - Maximum observed plasma concentration |
| AUC0-τ | 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 | 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 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo PLC, Placebo | 8 |
| Group 1 - BIA 2-093 200 mg b.i.d. BIA 2-093, ESL, Eslicarbazepine acetate 200mg (twice daily) | 6 |
| Group 2 - BIA 2-093 400 mg o.d. BIA 2-093, ESL, Eslicarbazepine acetate 400mg | 6 |
| Group 3 - BIA 2-093 800 mg o.d. BIA 2-093, ESL, Eslicarbazepine acetate 800mg | 6 |
| Group 4 - BIA 2-093 1200 mg o.d. BIA 2-093, ESL, Eslicarbazepine acetate 1200mg | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | Placebo | Group 1 - BIA 2-093 200 mg b.i.d. | Group 2 - BIA 2-093 400 mg o.d. | Group 3 - BIA 2-093 800 mg o.d. | Group 4 - BIA 2-093 1200 mg o.d. | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 4 / 6 | 4 / 6 | 3 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Total Number of Adverse Events
Total Number of Adverse Events.
Time frame: up to 20 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | Total Number of Adverse Events | AE Considered Possibly Related to Treatment | 6 Total Number of AE |
| Group 1 - BIA 2-093 200 mg b.i.d. | Total Number of Adverse Events | AE Considered Not Related to Treatment | 3 Total Number of AE |
| Group 1 - BIA 2-093 200 mg b.i.d. | Total Number of Adverse Events | All Adverse Events | 9 Total Number of AE |
| Group 1 - BIA 2-093 200 mg b.i.d. | Total Number of Adverse Events | Adverse Events of Moderate Severity | 0 Total Number of AE |
| Group 1 - BIA 2-093 200 mg b.i.d. | Total Number of Adverse Events | Adverse Events of Mild Severity | 9 Total Number of AE |
| Group 2 - BIA 2-093 400 mg o.d. | Total Number of Adverse Events | Adverse Events of Mild Severity | 15 Total Number of AE |
| Group 2 - BIA 2-093 400 mg o.d. | Total Number of Adverse Events | All Adverse Events | 15 Total Number of AE |
| Group 2 - BIA 2-093 400 mg o.d. | Total Number of Adverse Events | AE Considered Not Related to Treatment | 2 Total Number of AE |
| Group 2 - BIA 2-093 400 mg o.d. | Total Number of Adverse Events | AE Considered Possibly Related to Treatment | 13 Total Number of AE |
| Group 2 - BIA 2-093 400 mg o.d. | Total Number of Adverse Events | Adverse Events of Moderate Severity | 0 Total Number of AE |
| Group 3 - BIA 2-093 800 mg o.d. | Total Number of Adverse Events | Adverse Events of Moderate Severity | 1 Total Number of AE |
| Group 3 - BIA 2-093 800 mg o.d. | Total Number of Adverse Events | AE Considered Possibly Related to Treatment | 5 Total Number of AE |
| Group 3 - BIA 2-093 800 mg o.d. | Total Number of Adverse Events | Adverse Events of Mild Severity | 4 Total Number of AE |
| Group 3 - BIA 2-093 800 mg o.d. | Total Number of Adverse Events | AE Considered Not Related to Treatment | 0 Total Number of AE |
| Group 3 - BIA 2-093 800 mg o.d. | Total Number of Adverse Events | All Adverse Events | 5 Total Number of AE |
| Group 4 - BIA 2-093 1200 mg o.d. | Total Number of Adverse Events | AE Considered Not Related to Treatment | 0 Total Number of AE |
| Group 4 - BIA 2-093 1200 mg o.d. | Total Number of Adverse Events | Adverse Events of Moderate Severity | 0 Total Number of AE |
| Group 4 - BIA 2-093 1200 mg o.d. | Total Number of Adverse Events | AE Considered Possibly Related to Treatment | 12 Total Number of AE |
| Group 4 - BIA 2-093 1200 mg o.d. | Total Number of Adverse Events | All Adverse Events | 12 Total Number of AE |
| Group 4 - BIA 2-093 1200 mg o.d. | Total Number of Adverse Events | Adverse Events of Mild Severity | 12 Total Number of AE |
| Placebo | Total Number of Adverse Events | Adverse Events of Mild Severity | 14 Total Number of AE |
| Placebo | Total Number of Adverse Events | Adverse Events of Moderate Severity | 0 Total Number of AE |
| Placebo | Total Number of Adverse Events | AE Considered Possibly Related to Treatment | 13 Total Number of AE |
| Placebo | Total Number of Adverse Events | All Adverse Events | 14 Total Number of AE |
| Placebo | Total Number of Adverse Events | AE Considered Not Related to Treatment | 1 Total Number of AE |
Secondary
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
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | AUC0-τ | AUC0-τ Day 1 | 22163 ng.h/ml | Standard Deviation 6216 |
| Group 1 - BIA 2-093 200 mg b.i.d. | AUC0-τ | AUC0-τ Day 8 | 63140 ng.h/ml | Standard Deviation 7997 |
| Group 2 - BIA 2-093 400 mg o.d. | AUC0-τ | AUC0-τ Day 8 | 126308 ng.h/ml | Standard Deviation 14833 |
| Group 2 - BIA 2-093 400 mg o.d. | AUC0-τ | AUC0-τ Day 1 | 96262 ng.h/ml | Standard Deviation 17064 |
| Group 3 - BIA 2-093 800 mg o.d. | AUC0-τ | AUC0-τ Day 1 | 159492 ng.h/ml | Standard Deviation 21695 |
| Group 3 - BIA 2-093 800 mg o.d. | AUC0-τ | AUC0-τ Day 8 | 268384 ng.h/ml | Standard Deviation 27683 |
| Group 4 - BIA 2-093 1200 mg o.d. | AUC0-τ | AUC0-τ Day 1 | 250426 ng.h/ml | Standard Deviation 27356 |
| Group 4 - BIA 2-093 1200 mg o.d. | AUC0-τ | AUC0-τ Day 8 | 423003 ng.h/ml | Standard Deviation 45952 |
Secondary
Cmax
Cmax - Maximum observed plasma concentration
Time frame: Day 1 and Day 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | Cmax | Cmax Day 1 | 3086 ng/ml | Standard Error 1342 |
| Group 1 - BIA 2-093 200 mg b.i.d. | Cmax | Cmax Day 8 | 6683 ng/ml | Standard Error 1576 |
| Group 2 - BIA 2-093 400 mg o.d. | Cmax | Cmax Day 8 | 8824 ng/ml | Standard Error 1411 |
| Group 2 - BIA 2-093 400 mg o.d. | Cmax | Cmax Day 1 | 7827 ng/ml | Standard Error 1313 |
| Group 3 - BIA 2-093 800 mg o.d. | Cmax | Cmax Day 1 | 11074 ng/ml | Standard Error 1919 |
| Group 3 - BIA 2-093 800 mg o.d. | Cmax | Cmax Day 8 | 18675 ng/ml | Standard Error 2613 |
| Group 4 - BIA 2-093 1200 mg o.d. | Cmax | Cmax Day 1 | 16071 ng/ml | Standard Error 2238 |
| Group 4 - BIA 2-093 1200 mg o.d. | Cmax | Cmax Day 8 | 25457 ng/ml | Standard Error 2746 |