Epilepsy
Conditions
Keywords
Eslicarbazepine acetate, BIA 2-093
Brief summary
The purpose of this study is to determine the effects of age on the pharmacokinetic profile of BIA 2-093 and its active metabolites.
Detailed description
This was a single-centre, open-label, parallel group, non-randomised study with a single-dose phase (Phase A) followed by a multiple-dose phase (Phase B), in 12 healthy elderly and 12 healthy young subjects. During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Interventions
DRUGBIA 2-093
During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Sponsors
Bial - Portela C S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects aged between 18 and 40 years, inclusive OR male or female subjects aged 65 years or more. * If young, subjects who were within 15% of ideal body weight OR, if elderly, subjects who were within 20% of ideal body weight according to the Metropolitan Life Insurance Table. * 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 acceptable to the Investigator. * Subjects who were negative for HBsAg, HCVAb and 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. * (If female) She was not of childbearing potential by reason of surgery or menopause or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine. * (If female and with less than 40 years old) She 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, 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 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 drugs within 2 weeks of first dosing. * Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study. * 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. * (If female) She was pregnant or breast-feeding * (If female) She was of childbearing potential and she did not use an authorised effective contraceptive method.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Drug Concentration (Cmax) | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax - Time of Maximum Observed Concentration | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 |
| AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p | Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093 |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Elderly Subjects 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. | 14 |
| Young Subjects 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. | 15 |
| Total | 29 |
Baseline characteristics
| Characteristic | Elderly Subjects | Young Subjects | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 0 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 14 | 11 / 15 |
| serious Total, serious adverse events | 1 / 14 | 0 / 16 |
Outcome results
Primary
Maximum Drug Concentration (Cmax)
Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093
Time frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Single dose (BIA 2-194) | 9469 ng/mL | Standard Deviation 2284 |
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (BIA 2-194) | 15067 ng/mL | Standard Deviation 2126 |
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Single dose (BIA 2-195) | 209 ng/mL | Standard Deviation 72.1 |
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (BIA 2-195) | 531 ng/mL | Standard Deviation 190 |
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Single dose (oxcarbazepine) | 76.3 ng/mL | Standard Deviation 29.5 |
| Elderly Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (oxcarbazepine) | 135 ng/mL | Standard Deviation 36.6 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Single dose (oxcarbazepine) | 77.3 ng/mL | Standard Deviation 15.6 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Single dose (BIA 2-194) | 9867 ng/mL | Standard Deviation 1714 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (BIA 2-195) | 461 ng/mL | Standard Deviation 132 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (BIA 2-194) | 17309 ng/mL | Standard Deviation 3430 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Multiple dose (oxcarbazepine) | 150 ng/mL | Standard Deviation 36.6 |
| Young Subjects | Maximum Drug Concentration (Cmax) | Single dose (BIA 2-195) | 192 ng/mL | Standard Deviation 31.5 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093
Time frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (BIA 2-194) | 190521 ng.h/mL | Standard Deviation 69082 |
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (BIA 2-194) | 288364 ng.h/mL | Standard Deviation 40878 |
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (BIA 2-195) | 5738 ng.h/mL | Standard Deviation 3675 |
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (BIA 2-195) | 15911 ng.h/mL | Standard Deviation 4852 |
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (oxcarbazepine) | 1014 ng.h/mL | Standard Deviation 965 |
| Elderly Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (oxcarbazepine) | 1508 ng.h/mL | Standard Deviation 725 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (oxcarbazepine) | 577 ng.h/mL | Standard Deviation 246 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (BIA 2-194) | 174713 ng.h/mL | Standard Deviation 37062 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (BIA 2-195) | 12782 ng.h/mL | Standard Deviation 3722 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (BIA 2-194) | 290630 ng.h/mL | Standard Deviation 68649 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Multiple dose (oxcarbazepine) | 1490 ng.h/mL | Standard Deviation 495 |
| Young Subjects | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | Single dose (BIA 2-195) | 3361 ng.h/mL | Standard Deviation 1295 |
Secondary
Tmax - Time of Maximum Observed Concentration
Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093
Time frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (BIA 2-195) | 7.29 hours | Standard Deviation 4.18 |
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (BIA 2-194) | 2.04 hours | Standard Deviation 0.916 |
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (oxcarbazepine) | 5.41 hours | Standard Deviation 3.29 |
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (BIA 2-195) | 13.6 hours | Standard Deviation 5.43 |
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (oxcarbazepine) | 2.67 hours | Standard Deviation 1.54 |
| Elderly Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (BIA 2-194) | 2.96 hours | Standard Deviation 1.25 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (oxcarbazepine) | 2.67 hours | Standard Deviation 1.48 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (BIA 2-194) | 3.00 hours | Standard Deviation 1.81 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (BIA 2-195) | 11.3 hours | Standard Deviation 6.57 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (BIA 2-195) | 7.58 hours | Standard Deviation 2.68 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Single dose (oxcarbazepine) | 5.41 hours | Standard Deviation 2.96 |
| Young Subjects | Tmax - Time of Maximum Observed Concentration | Multiple dose (BIA 2-194) | 2.04 hours | Standard Deviation 1.57 |