Epilepsy
Conditions
Keywords
Eslicarbazepine acetate, BIA 2-093
Brief summary
The purpose of this study is to investigate the effects of multiple-dose administration of BIA 2-093 on the steady-state pharmacokinetics of digoxin in healthy subjects.
Detailed description
Single centre, multiple-dose, double-blind, randomised, placebo-controlled, two-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout of 10 or more days. During each of the treatment periods the volunteers received either a daily oral dose of BIA 2-093 1200 mg once-daily (od) or matching placebo, concomitantly with a dose of digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).
Interventions
DRUGBIA 2-093
BIA 2-093 1200 mg once-daily
DRUGPlacebo
matching placebo
DRUGDigoxin
Digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects aged between 18 and 45 years, inclusive. * Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive. * Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG. * Subjects who had clinical laboratory tests clinically acceptable. * Subjects who were negative for HBs Ag, anti-HCV Ab and anti-HIV-1 and HIV-2 Ab tests at screening. * Subjects who were negative for alcohol and drugs of abuse at screening. * Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day. * Subjects who were able and willing to give written informed consent. * In case of female volunteers, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, used one of the following methods of contraception: double-barrier or intrauterine device. * In case of female volunteers, subjects who had a negative pregnancy test at screening.
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, 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 any of the following findings on the ECG: QTc interval \>440 msec; first-, second- or third-degree atrioventricular block; atrial fibrillation; heart rate below 50 bpm; any other relevant abnormality. * 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 used prescription drugs within 4 weeks of first dosing. * Subjects who had used over the counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing. * Subjects who had used any investigational drug and/or participated in any clinical trial within 2 months of their first admission. * Subjects who had previously received BIA 2-093. * Subjects who had donated and/or received any blood or blood products within the previous 2 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. * In case of female volunteers, subjects who were pregnant or breast-feeding. * In case of female volunteers, subjects who were of childbearing potential and did not use an authorized effective contraceptive method.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Steady-state Plasma Concentration | Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose | Cmax - Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax - Time of Occurrence of Cmax at Steady-state | Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose | Time of Occurrence of Cmax Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin |
| AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h | Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose | Steady-state Area Under the Plasma Concentration-time Profile Over 24 h of BIA 2-005 (BIA 2-093 metabolite) and Digoxin |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 2-093 + Placebo Period 1:
BIA 2-093 1200 mg with:
Days 1 and 2: once-daily 0.50 mg digoxin Days 3 to 8: once-daily 0.25 mg odigoxin
Period 2:
Placebo with:
Days 1 and 2: once-daily 0.50 mg digoxin Days 3 to 8: once-daily 0.25 mg odigoxin | 7 |
| Placebo + BIA 2-093 Period 1:
Placebo with:
Days 1 and 2: once-daily 0.50 mg digoxin Days 3 to 8: once-daily 0.25 mg odigoxin
Period 2:
BIA 2-093 1200 mg with:
Days 1 and 2: once-daily 0.50 mg digoxin Days 3 to 8: once-daily 0.25 mg odigoxin | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | BIA 2-093 + Placebo | Placebo + BIA 2-093 | 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 | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 13 | 6 / 13 |
| serious Total, serious adverse events | 1 / 13 | 0 / 13 |
Outcome results
Primary
Cmax - Maximum Steady-state Plasma Concentration
Cmax - Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin
Time frame: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 + Placebo | Cmax - Maximum Steady-state Plasma Concentration | Cmax (Digoxin) (Digoxin+BIA 2-093) | 1,909 ng/mL | — |
| BIA 2-093 + Placebo | Cmax - Maximum Steady-state Plasma Concentration | Cmax (BIA 2-005) | 27571 ng/mL | Standard Deviation 8252 |
| BIA 2-093 + Placebo | Cmax - Maximum Steady-state Plasma Concentration | Cmax (Digoxin) (Digoxin+Placebo) | 2,350 ng/mL | — |
Secondary
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h
Steady-state Area Under the Plasma Concentration-time Profile Over 24 h of BIA 2-005 (BIA 2-093 metabolite) and Digoxin
Time frame: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 + Placebo | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h | AUCτ (BIA 2-005) | 370297 ng*h/mL | Standard Deviation 79388 |
| BIA 2-093 + Placebo | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h | AUCτ (Digoxin) (Digoxin+Placebo) | 17607 ng*h/mL | Standard Deviation 5599 |
| BIA 2-093 + Placebo | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h | AUCτ (Digoxin) (Digoxin+BIA 2-093) | 16595 ng*h/mL | Standard Deviation 3801 |
Secondary
Tmax - Time of Occurrence of Cmax at Steady-state
Time of Occurrence of Cmax Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin
Time frame: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIA 2-093 + Placebo | Tmax - Time of Occurrence of Cmax at Steady-state | tmax (BIA 2-005) | 2 hours |
| BIA 2-093 + Placebo | Tmax - Time of Occurrence of Cmax at Steady-state | tmax (Digoxin) (Digoxin+placebo) | 1 hours |
| BIA 2-093 + Placebo | Tmax - Time of Occurrence of Cmax at Steady-state | tmax (Digoxin) (Digoxin+BIA 2-093) | 1 hours |