Partial Epilepsy
Conditions
Keywords
Partial, Epilepsy, Eslicarbazepine acetate, Pharmacokinetics, Tolerability
Brief summary
This purpose of this study is to measure the concentrations of two anti-epileptic drugs (Eslicarbazepine acetate and oxcarbazepine) and their metabolites in the cerebrospinal fluid and blood plasma of healthy subjects and also to assess how these drugs are tolerated.
Interventions
Oral administration 600 mg QD morning from Day 1-3 and 1200 mg from Day 4-9
DRUGOxcarbazepine
Oxcarbazepine 300 mg BID from Day 1-3 (morning and evening) and oxcarbazepine 600mg BID from Day 4-9 (morning and evening, only morning dose on Day 9)
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects * Aged 18-55 years * Body mass index (18.5-29 kg/m3)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h | Cmax - Maximum plasma concentration CSF - Cerebral Spinal Fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate. |
| AUC0-t AUC From Time Zero to the Last Sampling Time | Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h | AUC0-t - area under the concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification CSF - cerebrospinal fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eslicarbazepine Acetate Eslicarbazepine acetate (ESL) 600 mg QD morning from Day 1-3 and 1200 mg ESL QD morning from Day 4-9
Eslicarbazepine acetate: Oral administration 600 mg QD morning from Day 1-3 and 1200 mg from Day 4-9 | 7 |
| Oxcarbazepine Oxcarbazepine 300 mg BID from Day 1-3 and oxcarbazepine 600mg BID from Day 4-9
Oxcarbazepine: Oxcarbazepine 300 mg BID from Day 1-3 (morning and evening) and oxcarbazepine 600mg BID from Day 4-9 (morning and evening, only morning dose on Day 9) | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Eslicarbazepine Acetate | Oxcarbazepine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
AUC0-t AUC From Time Zero to the Last Sampling Time
AUC0-t - area under the concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification CSF - cerebrospinal fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate.
Time frame: Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-194) plasma | 340123 ng.h/mL | Standard Deviation 70412 |
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-195) plasma | 18743 ng.h/mL | Standard Deviation 4620 |
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (Oxcarbazepine) plasma | 3377 ng.h/mL | Standard Deviation 762 |
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-194) CSF | 154509 ng.h/mL | Standard Deviation 22495 |
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-195) CSF | 11791 ng.h/mL | Standard Deviation 2909 |
| Eslicarbazepine Acetate | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (Oxcarbazepine) CSF | 1522 ng.h/mL | Standard Deviation 287 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-195) CSF | 23996 ng.h/mL | Standard Deviation 3495 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-194) plasma | 164726 ng.h/mL | Standard Deviation 29904 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-194) CSF | 86187 ng.h/mL | Standard Deviation 9545 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (BIA 2-195) plasma | 39034 ng.h/mL | Standard Deviation 7094 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (Oxcarbazepine) CSF | 2485 ng.h/mL | Standard Deviation 400 |
| Oxcarbazepine | AUC0-t AUC From Time Zero to the Last Sampling Time | AUC0-t (Oxcarbazepine) plasma | 7135 ng.h/mL | Standard Deviation 2561 |
Primary
Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid
Cmax - Maximum plasma concentration CSF - Cerebral Spinal Fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate.
Time frame: Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-194) plasma | 23932 ng/mL | Standard Deviation 6630 |
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-195) plasma | 886 ng/mL | Standard Deviation 235 |
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (Oxcarbazepine) plasma | 245 ng/mL | Standard Deviation 72.6 |
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-194) CSF | 7559 ng/mL | Standard Deviation 1050 |
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-195) CSF | 538 ng/mL | Standard Deviation 145 |
| Eslicarbazepine Acetate | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (Oxcarbazepine) CSF | 93.2 ng/mL | Standard Deviation 27 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-195) CSF | 2146 ng/mL | Standard Deviation 327 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-194) plasma | 16162 ng/mL | Standard Deviation 2662 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-194) CSF | 7566 ng/mL | Standard Deviation 912 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (BIA 2-195) plasma | 4039 ng/mL | Standard Deviation 613 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (Oxcarbazepine) CSF | 448 ng/mL | Standard Deviation 109 |
| Oxcarbazepine | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid | Cmax (Oxcarbazepine) plasma | 1990 ng/mL | Standard Deviation 941 |