Epilepsy
Conditions
Keywords
Anticonvulsant
Brief summary
Single centre, double-blind, randomised, placebo-controlled study of two dosage regimens of BIA 2-093 - 1800 mg (Group 1) and 2400 mg (Group 2) - in two groups of healthy male volunteers
Detailed description
Within each group (n=9) 3 volunteers were randomised to receive placebo and the remaining 6 volunteers to receive BIA 2-093. No volunteer was a member of more than one treatment group. In each group, the study consisted of a single-dose period (Phase A) followed by a 7-day multiple-dose period (Phase B). The multiple-dose phase started 96 h post single-dose. Progression to the 2400 mg dose (Group 2) only occurred if the 1800 mg dose (Group 1) was considered to be safe and well tolerated. An appropriate interval separated the investigation of the two groups in order to permit a timely review and evaluation of safety data. Treatment consisted of a single-dose (Phase A) followed by a once-daily dose for 7 days (Phase B). Doses were prepared as follows: Group 1 = 3 tablets of BIA 2-093 600 mg plus 1 placebo tablet, or 4 placebo tablets; Group 2 = 4 tablets of BIA 2-093 600 mg, or 4 placebo tablets.
Interventions
DRUGBIA 2-093 - 1800 mg (Group 1)
3 tablets of BIA 2-093
DRUGBIA 2-093 - 2400 mg (Group 2)
4 tablets of BIA 2-093 600 mg
DRUGPlacebo
placebo tablets
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male 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 within normal ranges 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 smoked less than 10 cigarettes or equivalent per day. * Subjects who were able and willing to give written informed consent.
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. * 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. * Subjects who had acute gastrointestinal symptoms at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn). * Subjects who had used prescription or over-the-counter medication within 2 weeks of admission. * Subjects who had used any investigational drug or participated in any clinical trial within 3 months of admission. * Subjects who had previously received BIA 2-093. * Subjects who had donated or received any blood or blood products within the previous 3 months prior to screening. * Subjects who were vegetarians, vegans 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events Reported | 3 weeks | investigate the tolerability of two single- and multiple-dose regimens of BIA 2-093 (1800 mg and 2400 mg)considering the Number of adverse events reported by patient |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Drug Concentration | Day 1 and Day 7 | Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite |
| Tmax - the Time of Occurrence of Cmax | Day 1 and Day 7 | Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite |
| AUC0-τ | Day 1 and Day 7 | Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 2-093 - 1800 mg (Group 1) 3 tablets of BIA 2-093 600 mg
BIA 2-093 - 1800 mg (Group 1): 3 tablets of BIA 2-093 | 6 |
| BIA 2-093 - 2400 mg (Group 2) 4 tablets of BIA 2-093 600 mg
BIA 2-093 - 2400 mg (Group 2): 4 tablets of BIA 2-093 600 mg | 6 |
| Placebo PLC, Placebo | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | BIA 2-093 - 1800 mg (Group 1) | BIA 2-093 - 2400 mg (Group 2) | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 4 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Adverse Events Reported
investigate the tolerability of two single- and multiple-dose regimens of BIA 2-093 (1800 mg and 2400 mg)considering the Number of adverse events reported by patient
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIA 2-093 - 1800 mg (Group 1) | Number of Adverse Events Reported | 10 Number of adverse events reported |
| BIA 2-093 - 2400 mg (Group 2) | Number of Adverse Events Reported | 7 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | 7 Number of adverse events reported |
Secondary
AUC0-τ
Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite
Time frame: Day 1 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 - 1800 mg (Group 1) | AUC0-τ | AUC0-τ (BIA 2-005) single dose | 507563 ng.h/mL | Standard Deviation 86363 |
| BIA 2-093 - 1800 mg (Group 1) | AUC0-τ | AUC0-τ (BIA 2-005) multiple dose | 740299 ng.h/mL | Standard Deviation 144882 |
| BIA 2-093 - 1800 mg (Group 1) | AUC0-τ | AUC0-τ (oxcarbazepine) single dose | 3589 ng.h/mL | Standard Deviation 847 |
| BIA 2-093 - 1800 mg (Group 1) | AUC0-τ | AUC0-τ (oxcarbazepine) multiple dose | 6958 ng.h/mL | Standard Deviation 1824 |
| BIA 2-093 - 2400 mg (Group 2) | AUC0-τ | AUC0-τ (oxcarbazepine) multiple dose | 9956 ng.h/mL | Standard Deviation 2329 |
| BIA 2-093 - 2400 mg (Group 2) | AUC0-τ | AUC0-τ (BIA 2-005) single dose | 445596 ng.h/mL | Standard Deviation 116306 |
| BIA 2-093 - 2400 mg (Group 2) | AUC0-τ | AUC0-τ (oxcarbazepine) single dose | 4547 ng.h/mL | Standard Deviation 1512 |
| BIA 2-093 - 2400 mg (Group 2) | AUC0-τ | AUC0-τ (BIA 2-005) multiple dose | 905860 ng.h/mL | Standard Deviation 115783 |
Secondary
Cmax - Maximum Observed Plasma Drug Concentration
Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite
Time frame: Day 1 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 - 1800 mg (Group 1) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-005) single dose | 34569 ng/mL | Standard Deviation 5623 |
| BIA 2-093 - 1800 mg (Group 1) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-005) multiple dose | 47665 ng/mL | Standard Deviation 11108 |
| BIA 2-093 - 1800 mg (Group 1) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (oxcarbazepine) single dose | 241 ng/mL | Standard Deviation 57.1 |
| BIA 2-093 - 1800 mg (Group 1) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (oxcarbazepine) multiple dose | 361 ng/mL | Standard Deviation 106 |
| BIA 2-093 - 2400 mg (Group 2) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (oxcarbazepine) multiple dose | 734 ng/mL | Standard Deviation 186 |
| BIA 2-093 - 2400 mg (Group 2) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-005) single dose | 35926 ng/mL | Standard Deviation 15301 |
| BIA 2-093 - 2400 mg (Group 2) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (oxcarbazepine) single dose | 508 ng/mL | Standard Deviation 177 |
| BIA 2-093 - 2400 mg (Group 2) | Cmax - Maximum Observed Plasma Drug Concentration | Cmax (BIA 2-005) multiple dose | 56506 ng/mL | Standard Deviation 11277 |
Secondary
Tmax - the Time of Occurrence of Cmax
Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite
Time frame: Day 1 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 - 1800 mg (Group 1) | Tmax - the Time of Occurrence of Cmax | tmax (BIA 2-005) single dose | 3.8 hours | Standard Deviation 1.2 |
| BIA 2-093 - 1800 mg (Group 1) | Tmax - the Time of Occurrence of Cmax | tmax (BIA 2-005) multiple dose | 2.1 hours | Standard Deviation 1.2 |
| BIA 2-093 - 1800 mg (Group 1) | Tmax - the Time of Occurrence of Cmax | tmax (oxcarbazepine) single dose | 4.67 hours | Standard Deviation 1.03 |
| BIA 2-093 - 1800 mg (Group 1) | Tmax - the Time of Occurrence of Cmax | tmax (oxcarbazepine) multiple dose | 3.83 hours | Standard Deviation 1.17 |
| BIA 2-093 - 2400 mg (Group 2) | Tmax - the Time of Occurrence of Cmax | tmax (oxcarbazepine) multiple dose | 3.67 hours | Standard Deviation 0.52 |
| BIA 2-093 - 2400 mg (Group 2) | Tmax - the Time of Occurrence of Cmax | tmax (BIA 2-005) single dose | 3.3 hours | Standard Deviation 1.7 |
| BIA 2-093 - 2400 mg (Group 2) | Tmax - the Time of Occurrence of Cmax | tmax (oxcarbazepine) single dose | 4.00 hours | Standard Deviation 1.1 |
| BIA 2-093 - 2400 mg (Group 2) | Tmax - the Time of Occurrence of Cmax | tmax (BIA 2-005) multiple dose | 3.6 hours | Standard Deviation 2.7 |