Epilepsy
Conditions
Brief summary
Single centre, open-label, multiple doses, one-sequence design study in two parallel groups of healthy volunteers
Detailed description
Single centre, open-label, multiple doses, one-sequence design study in two parallel groups of healthy volunteers: Group A: Pre-treatment with ESL, treatment with ESL and ascending doses of Topamax (TPM) in last phases; Group B: Pre-treatment with TPM, treatment with TPM and ascending doses of ESL in last phases
Interventions
DRUGBIA 2-093
DRUGTopamax
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer * Male aged of at least 18 years but not older than 45 years with a body mass índex (BMI) greater than or equal to 19 and below 30 kg/m * Clinical laboratory values within the laboratory's stated normal range; i f not within this range, they must be without any clinical significance (laboratory tests are presented in section 6.1.1.3) * Healthy according to the medical history, laboratory results and physical * Light-, non- or ex-smokers. A light smoker is defined as someone smoking 1 0 cigarettes or less per day, and an ex-smoker i s defined as someone who completely stopped smoking for at least 1 2 months before day 1 of this study
Exclusion criteria
* Significant history of hypersensitivity to topiramate, eslicarbazepine, oxcarbazepine, carbamazepine or any related products (including excipients of the formulations) as wel l as severe hypersensitivity reactions (like angioedema) to any drugs * Presence of significant gastrointestinal, l iver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects * History of significant gastrointestinal, liver o r kidney disease, o r surgery that may affect drug bioavailability, including but not limited to cholecystectomy * Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic d isease * Presence o f significant heart disease o r disorder according to ECG * Presence or history of significant central nervous system disorder l ike convulsion or depression * Presence o r history o f significant ocular disease * Presence or history of severe hepatic impairment * Presence or history of renal insufficiency (serum creatinine level greater than 135 μmol/L) * History or presence of acidosis * Use of valproic acid in the previous 7 days prior to Day 1 of the study. * Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) * Any clinically significant illness in the previous 28 days before day 1 of this study * Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin and rifampin), in the previous 28 days before Day 1 of this study * Participation in another clinical trial or donation of 50 mL or more of blood in the previous 28 days before day 1 of this study * Donation of 500 mL or more of blood (Canadian B lood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study * Positive urine screening of drugs of abuse (drugs listing is presented in section 6.1.1.4). * Positive results to HIV, HBsAg or anti-HCV tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - the Maximum Plasma Concentration | Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h | BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate |
| Tmax - the Time of Occurrence of Cmax | Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h | BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate Both Groups A and B described in participant flow recieved BIA 2-093 and Topiramate. The results presented here are related with the different interventions in both groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. | Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h | BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A BIA 2-093 + Topamax Group A
* Pre-treatment: 600 mg once daily dose of eslicarbazepine acetate (ESL) administered for two consecutive days;
* Treatment 1: 1200 mg once daily dose of eslicarbazepine acetate (ESL) administered for six consecutive days
* Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg for two consecutive days
* Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg (morning) + 100mg (evening) for two consecutive days
* Treatment 4: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200 mg for fifteen consecutive days
BIA 2-093
Topamax | 13 |
| Group B BIA 2-093 + Topamax * Pre-treatment: 100 mg once daily dose of TPM administered for two consecutive days;
* Pre-treatment 2: 100 mg twice daily dose of TPM administered for two consecutive days;
* Treatment: 200 mg once daily dose of TPM administered for four consecutive days;
* Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 600 mg and TPM 200 mg for two consecutive days
* Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200mg for seventeen consecutive days
BIA 2-093
Topamax | 14 |
| Total | 27 |
Baseline characteristics
| Characteristic | Group A BIA 2-093 + Topamax | Group B BIA 2-093 + Topamax | 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 | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 16 | 13 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Cmax - the Maximum Plasma Concentration
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate
Time frame: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 + TPM | Cmax - the Maximum Plasma Concentration | Cmax (BIA 2-194) | 21960.6 ng/mL | Standard Deviation 2482 |
| BIA 2-093 + TPM | Cmax - the Maximum Plasma Concentration | Cmax (BIA 2-195) | 931.8 ng/mL | Standard Deviation 216 |
| BIA 2-093 | Cmax - the Maximum Plasma Concentration | Cmax (BIA 2-194) | 25414.8 ng/mL | Standard Deviation 3736 |
| BIA 2-093 | Cmax - the Maximum Plasma Concentration | Cmax (BIA 2-195) | 1062.6 ng/mL | Standard Deviation 235 |
Primary
Tmax - the Time of Occurrence of Cmax
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate Both Groups A and B described in participant flow recieved BIA 2-093 and Topiramate. The results presented here are related with the different interventions in both groups
Time frame: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 + TPM | Tmax - the Time of Occurrence of Cmax | Tmax (BIA 2-194) | 2.00 hours | Standard Deviation 0.96 |
| BIA 2-093 + TPM | Tmax - the Time of Occurrence of Cmax | Tmax (BIA 2-195) | 9.00 hours | Standard Deviation 4.2 |
| BIA 2-093 | Tmax - the Time of Occurrence of Cmax | Tmax (BIA 2-194) | 2.00 hours | Standard Deviation 0.97 |
| BIA 2-093 | Tmax - the Time of Occurrence of Cmax | Tmax (BIA 2-195) | 6.00 hours | Standard Deviation 3.91 |
Secondary
AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State.
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate
Time frame: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 + TPM | AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. | AUCτ (BIA 2-195) | 19611.8 ng*h/mL | Standard Deviation 4707 |
| BIA 2-093 + TPM | AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. | AUCτ (BIA 2-194) | 361733.9 ng*h/mL | Standard Deviation 38706 |
| BIA 2-093 | AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. | AUCτ (BIA 2-194) | 389794.3 ng*h/mL | Standard Deviation 35861 |
| BIA 2-093 | AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. | AUCτ (BIA 2-195) | 22886.8 ng*h/mL | Standard Deviation 5195 |