Epilepsy
Conditions
Brief summary
Single-centre, open-label, randomized, two-sequence, two-way crossover study. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 10 to 14 days or more.
Detailed description
Single-centre, open-label, randomized, two-sequence, two-way crossover study. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 10 to 14 days or more. In Group 1 the volunteers received a single oral dose of 25 mg OPC. In Group 2 the volunteers received a single oral dose of 50 mg OPC
Interventions
DRUGBIA 9-1067
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects aged 18 to 45 years, inclusive; * Body mass index (BMI) between 19 and 30 kg/m²; * Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination, and 12-lead ECG; - Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C vírus (anti-HCV) antibodies, and anti-human immunodeficiency virus (HIV)-1/-2 antibodies at screening; * Clinical laboratory test results clinically acceptable at screening and admission to each treatment period; * Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period; * Non-smokers or ex-smokers for at least 3 months; * Able and willing to give written informed consent; * If female: She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used an effective nonhormonal method of contraception (intrauterine device or intrauterine system; condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he was the sole partner of that subject) for all the duration of the study; and she had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 of each treatment period.
Exclusion criteria
* 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; * A clinically relevant surgical history; * Any clinically relevant abnormality in the coagulation tests; * Any clinically relevant abnormality in the liver function tests. If the subject had a borderline clinically relevant abnormality that was not considered clinically significant, a retest could be done after discussion with the sponsor's medical monitor; * A history of relevant atopy or drug hypersensitivity; * A history of alcoholism or drug abuse; * Consume more than 14 units of alcohol a week; * A significant infection or known inflammatory process on screening or admission to each treatment period; * Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period; * Used medicines within 2 weeks of admission to first period that could have affected the subject's safety or other study assessments in the investigator's opinion; * Previously received OPC. Previous use of OPC was documented by questioning the subjects; * Used any investigational drug or participated in any clinical trial within 90 days prior to screening * Participated in more than 2 clinical trials within the 12 months prior to screening; * Donated or received any blood or blood products within the 3 months prior to screening; * Vegetarians, vegans or have medical dietary restrictions; * Not able to communicate reliably with the investigator; * Unlikely to co-operate with the requirements of the study; unwilling or unable to give written informed consent; * If female: she was pregnant or breast-feeding; she had a positive serum pregnancy test; she was of childbearing potential and did not use an accepted effective contraceptive method or she used oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Concentration of 9-1067 | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose | Cmax - maximum observed plasma concentration of 9-1067. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax - Time of Occurrence of Cmax of 9-1067 | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose | tmax - time of occurrence of Maximum Observed Plasma Concentration of 9-1067 |
| AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose | — |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose | AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 BIA 9-1067 25 mg Period 1 - 5x5 mg OPC Period 2 - 1x25 mg OPC
BIA 9-1067 | 14 |
| Group 2 BIA 9-1067 25 mg Period 1 - 1x25 mg OPC Period 2 - 5x5 mg OPC
BIA 9-1067 | 14 |
| Group 1 BIA 9-1067 50 mg Period 1 - 2x25 mg OPC Period 2 - 1x50 mg OPC
BIA 9-1067 | 14 |
| Group 2 BIA 9-1067 50 mg Period 1 - 1x50 mg OPC Period 2 - 2x25 mg OPC
BIA 9-1067 | 14 |
| Total | 56 |
Baseline characteristics
| Characteristic | Group 1 BIA 9-1067 25 mg | Group 2 BIA 9-1067 25 mg | Group 1 BIA 9-1067 50 mg | Group 2 BIA 9-1067 50 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 14 Participants | 14 Participants | 56 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 28 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 27 | 11 / 28 | 12 / 28 | 15 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Concentration of 9-1067
Cmax - maximum observed plasma concentration of 9-1067.
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5x5mg BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration of 9-1067 | 600 ng/mL | Standard Deviation 221 |
| 1x25 mg BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration of 9-1067 | 567 ng/mL | Standard Deviation 222 |
| 2x25 mg BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration of 9-1067 | 955 ng/mL | Standard Deviation 297 |
| 1x50 mg BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration of 9-1067 | 917 ng/mL | Standard Deviation 426 |
Secondary
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity
AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity.
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5x5mg BIA 9-1067 | AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | 1679 h.ng/mL | Standard Deviation 586 |
| 1x25 mg BIA 9-1067 | AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | 1539 h.ng/mL | Standard Deviation 554 |
| 2x25 mg BIA 9-1067 | AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | 2699 h.ng/mL | Standard Deviation 1012 |
| 1x50 mg BIA 9-1067 | AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | 2612 h.ng/mL | Standard Deviation 1082 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5x5mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t | 1603 h.ng/mL | Standard Deviation 566 |
| 1x25 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t | 1461 h.ng/mL | Standard Deviation 529 |
| 2x25 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t | 2669 h.ng/mL | Standard Deviation 945 |
| 1x50 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t | 2539 h.ng/mL | Standard Deviation 1066 |
Secondary
Tmax - Time of Occurrence of Cmax of 9-1067
tmax - time of occurrence of Maximum Observed Plasma Concentration of 9-1067
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5x5mg BIA 9-1067 | Tmax - Time of Occurrence of Cmax of 9-1067 | 2.00 hours |
| 1x25 mg BIA 9-1067 | Tmax - Time of Occurrence of Cmax of 9-1067 | 2.00 hours |
| 2x25 mg BIA 9-1067 | Tmax - Time of Occurrence of Cmax of 9-1067 | 2.00 hours |
| 1x50 mg BIA 9-1067 | Tmax - Time of Occurrence of Cmax of 9-1067 | 2.00 hours |