Parkinson Disease
Conditions
Keywords
Parkinson Disease, BIA 9-1067
Brief summary
The purpose of this study is to investigate the effect of BIA 9-1067 on rasagiline 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
DRUGrasagiline
1 mg rasagiline (single-dose)
DRUGBIA 9-1067
50 mg BIA 9-1067 (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 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 |
|---|---|
| Tmax - Time of Occurrence of Cmax | pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose |
| 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: rasagiline 1 mg Period 2: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 3: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg
rasagiline: 1 mg rasagiline (single-dose)
BIA 9-1067: 50 mg BIA 9-1067 (single-dose) | 8 |
| Group 2 Period 1: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 2: rasagiline 1 mg Period 3: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg
rasagiline: 1 mg rasagiline (single-dose)
BIA 9-1067: 50 mg BIA 9-1067 (single-dose) | 8 |
| Group 3 Period 1: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 2: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 3: rasagiline 1 mg
rasagiline: 1 mg rasagiline (single-dose)
BIA 9-1067: 50 mg BIA 9-1067 (single-dose) | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Group 1 | Total | Group 3 | Group 2 |
|---|---|---|---|---|
| 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 | 8 Participants | 24 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 12 Participants | 4 Participants | 4 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 | 1 / 24 | 6 / 24 | 3 / 24 | 3 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Cmax - Maximum Observed Plasma 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 |
|---|---|---|---|---|
| Rasagiline Alone | Cmax - Maximum Observed Plasma Concentration | BIA 9-1067 | NA ng/mL | — |
| Rasagiline Alone | Cmax - Maximum Observed Plasma Concentration | Rasagiline | 6152 ng/mL | Standard Deviation 2245 |
| Rasagiline 1 h After BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration | BIA 9-1067 | 672 ng/mL | Standard Deviation 226 |
| Rasagiline 1 h After BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration | Rasagiline | 6.058 ng/mL | Standard Deviation 2.399 |
| Rasagiline Concomitant BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration | BIA 9-1067 | 643 ng/mL | Standard Deviation 232 |
| Rasagiline Concomitant BIA 9-1067 | Cmax - Maximum Observed Plasma Concentration | Rasagiline | 6.078 ng/mL | Standard Deviation 2.255 |
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 |
|---|---|---|---|---|
| Rasagiline Alone | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | NA ng.h/mL | — |
| Rasagiline Alone | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | 4.323 ng.h/mL | Standard Deviation 0.9727 |
| Rasagiline 1 h After BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 2133 ng.h/mL | Standard Deviation 964.1 |
| Rasagiline 1 h After BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | 4.431 ng.h/mL | Standard Deviation 1.01 |
| Rasagiline Concomitant BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 1980 ng.h/mL | Standard Deviation 861.1 |
| Rasagiline Concomitant BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Rasagiline | 4.391 ng.h/mL | Standard Deviation 0.8782 |
Secondary
Tmax - Time of Occurrence of Cmax
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) |
|---|---|---|---|
| Rasagiline Alone | Tmax - Time of Occurrence of Cmax | BIA 9-1067 | NA hours |
| Rasagiline Alone | Tmax - Time of Occurrence of Cmax | Rasagiline | 0.50 hours |
| Rasagiline 1 h After BIA 9-1067 | Tmax - Time of Occurrence of Cmax | BIA 9-1067 | 2.00 hours |
| Rasagiline 1 h After BIA 9-1067 | Tmax - Time of Occurrence of Cmax | Rasagiline | 0.50 hours |
| Rasagiline Concomitant BIA 9-1067 | Tmax - Time of Occurrence of Cmax | BIA 9-1067 | 2.50 hours |
| Rasagiline Concomitant BIA 9-1067 | Tmax - Time of Occurrence of Cmax | Rasagiline | 0.50 hours |