Parkinson Disease
Conditions
Keywords
Parkinson Disease, BIA 9-1067
Brief summary
The purpose of this study is to investigate the effect of rasagiline on BIA 9-1067 pharmacokinetics in healthy subjects.
Detailed description
Single-centre, open-label, randomised, three-way crossover study consisting of 3 single-dose periods separated by a washout of 14 days or more
Interventions
DRUGBIA 9-1067
50 mg BIA 9-1067 (single-dose)
DRUGRasagiline
1 mg rasagiline (single-dose)
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who were able and willing to give written informed consent. * Male or female subjects aged between 18 and 45 years, inclusive. * Subjects of body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. * Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening * Subjects who had clinical laboratory test results clinically acceptable at screening and admission to each treatment period. * Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period. * Subjects who were non-smokers or ex-smokers for at least 3 months. * (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine device. * (If female) She had a negative pregnancy test (β-HCG) at screening and admission to each treatment period
Exclusion 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 any significant abnormality in the coagulation tests. * Subjects who had any significant abnormality in the liver function tests (a case-by-case decision for any abnormality was to be discussed with the Sponsor before inclusion). * Subjects who had a history of relevant atopy or 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 at screening or admission to each treatment period. * Subjects who had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period. * Subjects who had received fluoxetine within 5 weeks of admission to the first period. * Subjects who had used any other medicines within 2 weeks of admission to first period that could affected the safety or other study assessments, in the investigator's opinion. * Subjects who had previously received BIA 9-1067. * Subjects who have used any investigational drug or participated in any clinical trial within 90 days prior to screening. * Subjects who have donated or received any blood or blood products within the 3 months prior to screening. * Subjects who were vegetarians, vegans or have medical dietary restrictions. * Subjects who could not communicated 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 approved effective contraceptive method (double-barrier, intra-uterine device) or she uses oral contraceptives.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax - Maximum Observed Plasma Drug Concentration | pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Occurrence of Cmax (Tmax) | pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | 6-mL blood samples for the determination of plasma concentrations of BIA 9-1067 and/or rasagiline will be drawn by direct venipuncture or via an intravenous catheter into potassium ethylenediaminetetraacetic acid(EDTA)Vacutainers |
| AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Period 1: 50 mg BIA 9-1067 alone Period 2: 50 mg BIA 9-1067 1 h before a single dose of rasagiline 1 mg Period 3: 50 mg BIA 9-1067 alone concomitantly single dose of rasagiline 1 mg
BIA 9-1067: 50 mg BIA 9-1067 (single-dose)
Rasagiline: 1 mg rasagiline (single-dose) | 9 |
| Group 2 Period 1: 50 mg BIA 9-1067 1 h before a single dose of rasagiline 1 mg Period 2: 50 mg BIA 9-1067 alone Period 3: 50 mg BIA 9-1067 alone concomitantly single dose of rasagiline 1 mg
BIA 9-1067: 50 mg BIA 9-1067 (single-dose)
Rasagiline: 1 mg rasagiline (single-dose) | 8 |
| Group 3 Period 1: 50 mg BIA 9-1067 alone concomitantly single dose of rasagiline 1 mg Period 2: 50 mg BIA 9-1067 1 h before a single dose of rasagiline 1 mg Period 3: 50 mg BIA 9-1067 alone
BIA 9-1067: 50 mg BIA 9-1067 (single-dose)
Rasagiline: 1 mg rasagiline (single-dose) | 8 |
| Total | 25 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 8 Participants | 25 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 13 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 | 3 / 25 | 11 / 25 | 4 / 24 | 3 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Drug Concentration
Time frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 9-1067 Alone | Cmax - Maximum Observed Plasma Drug Concentration | BIA 9-1067 | 647 ng/mL | Standard Deviation 261 |
| BIA 9-1067 Alone | Cmax - Maximum Observed Plasma Drug Concentration | Rasagiline | NA ng/mL | — |
| BIA 9-1067 1h Before Rasagiline | Cmax - Maximum Observed Plasma Drug Concentration | BIA 9-1067 | 703 ng/mL | Standard Deviation 207 |
| BIA 9-1067 1h Before Rasagiline | Cmax - Maximum Observed Plasma Drug Concentration | Rasagiline | 4.260 ng/mL | Standard Deviation 1.81 |
| BIA 9-1067 Concomitant Rasagiline | Cmax - Maximum Observed Plasma Drug Concentration | BIA 9-1067 | 640 ng/mL | Standard Deviation 224 |
| BIA 9-1067 Concomitant Rasagiline | Cmax - Maximum Observed Plasma Drug Concentration | Rasagiline | 4.299 ng/mL | Standard Deviation 1.638 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration
Time frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 9-1067 Alone | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 1966 ng.h/mL | Standard Deviation 831.6 |
| BIA 9-1067 Alone | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | NA ng.h/mL | — |
| BIA 9-1067 1h Before Rasagiline | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 2182 ng.h/mL | Standard Deviation 794.2 |
| BIA 9-1067 1h Before Rasagiline | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | 3277 ng.h/mL | Standard Deviation 1114 |
| BIA 9-1067 Concomitant Rasagiline | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 2064 ng.h/mL | Standard Deviation 827.7 |
| BIA 9-1067 Concomitant Rasagiline | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | 3370 ng.h/mL | Standard Deviation 1115 |
Secondary
Time of Occurrence of Cmax (Tmax)
6-mL blood samples for the determination of plasma concentrations of BIA 9-1067 and/or rasagiline will be drawn by direct venipuncture or via an intravenous catheter into potassium ethylenediaminetetraacetic acid(EDTA)Vacutainers
Time frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIA 9-1067 Alone | Time of Occurrence of Cmax (Tmax) | BIA 9-1067 | 3.00 hours |
| BIA 9-1067 Alone | Time of Occurrence of Cmax (Tmax) | Rasagiline | NA hours |
| BIA 9-1067 1h Before Rasagiline | Time of Occurrence of Cmax (Tmax) | BIA 9-1067 | 3.00 hours |
| BIA 9-1067 1h Before Rasagiline | Time of Occurrence of Cmax (Tmax) | Rasagiline | 0.5 hours |
| BIA 9-1067 Concomitant Rasagiline | Time of Occurrence of Cmax (Tmax) | BIA 9-1067 | 2.50 hours |
| BIA 9-1067 Concomitant Rasagiline | Time of Occurrence of Cmax (Tmax) | Rasagiline | 0.5 hours |