Parkinson Disease
Conditions
Keywords
Parkinson Disease, BIA 9-1067
Brief summary
The purpose of this study is to investigate the CYP2C8 inhibition by BIA 9-1067.
Detailed description
Single-centre, open-label, randomised, two-way crossover study in healthy young male and female volunteers
Interventions
DRUGBIA 9-1067
25 mg BIA 9-1067 (single-dose)
DRUGRepaglinide
0.5 mg repaglinide (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
* 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 19 and 30 kg/m2, inclusive. * Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab 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. * (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 urine pregnancy test at screening and admission to each treatment period.
Exclusion criteria
* 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. * Clinically relevant surgical history. * Any abnormality in the coagulation tests. * Any abnormality in the liver function tests. * A history of relevant atopy or drug hypersensitivity. * History of alcoholism or drug abuse. * Consumed more than 14 units of alcohol a week. * Significant infection or known inflammatory process at 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. * Had used medicines within 2 weeks of admission to first period that may have affected the safety or other study assessments, in the investigator's opinion. * Had previously received BIA 9-1067. * Had used any investigational drug or participated in any clinical trial within 6 months prior to screening. * Had participated in more than 2 clinical trials within the 12 months prior to screening. * Had donated or received any blood or blood products within the 3 months prior to screening. * Vegetarians, vegans or had medical dietary restrictions. * Cannot communicate reliably with the investigator. * Unlikely to co-operate with the requirements of the study. * Unwilling or unable to gave written informed consent. * Employees at BIAL - Portela & Cª, S.A. * (If female) She was pregnant or breast-feeding. * (If female) She was of childbearing potential and she did not used an approved effective contraceptive method (double-barrier or intra-uterine device) or she used 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. |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity | 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
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Period 1: BIA 9-1067 + repaglinide Period 2: Repaglinide
BIA 9-1067: 25 mg BIA 9-1067 (single-dose)
Repaglinide: 0.5 mg repaglinide (single-dose) | 14 |
| Group 2 Period 1: Repaglinide Period 2: BIA 9-1067 + repaglinide
BIA 9-1067: 25 mg BIA 9-1067 (single-dose)
Repaglinide: 0.5 mg repaglinide (single-dose) | 13 |
| Total | 27 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | 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 | 14 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 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 | 7 / 24 | 8 / 27 |
| serious Total, serious adverse events | 0 / 24 | 0 / 27 |
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 |
|---|---|---|---|---|
| BIA 9-1067 + Repaglinide | Cmax - Maximum Observed Plasma Concentration | BIA 9-1067 | 400 ng/mL | Standard Deviation 245.2 |
| BIA 9-1067 + Repaglinide | Cmax - Maximum Observed Plasma Concentration | Repaglinide | 11.6 ng/mL | Standard Deviation 5.22 |
| Repaglinide | Cmax - Maximum Observed Plasma Concentration | BIA 9-1067 | NA ng/mL | — |
| Repaglinide | Cmax - Maximum Observed Plasma Concentration | Repaglinide | 9.76 ng/mL | Standard Deviation 5.42 |
Secondary
AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity
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 + Repaglinide | AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity | BIA 9-1067 | 1015 ng.h/mL | Standard Deviation 608 |
| BIA 9-1067 + Repaglinide | AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity | Repaglinide | 15.0 ng.h/mL | Standard Deviation 4.95 |
| Repaglinide | AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity | BIA 9-1067 | NA ng.h/mL | — |
| Repaglinide | AUC0-∞ - Area Under the Plasma Concentration-time Curve From Time 0 to Infinity | Repaglinide | 14.1 ng.h/mL | Standard Deviation 5.5 |
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 + Repaglinide | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | 979 ng.h/mL | Standard Deviation 607 |
| BIA 9-1067 + Repaglinide | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Repaglinide | 14.2 ng.h/mL | Standard Deviation 4.96 |
| Repaglinide | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | BIA 9-1067 | NA ng.h/mL | — |
| Repaglinide | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration | Repaglinide | 13.1 ng.h/mL | Standard Deviation 5.33 |
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) |
|---|---|---|---|
| BIA 9-1067 + Repaglinide | Tmax - Time of Occurrence of Cmax | BIA 9-1067 | 2.00 hours |
| BIA 9-1067 + Repaglinide | Tmax - Time of Occurrence of Cmax | Repaglinide | 0.5 hours |
| Repaglinide | Tmax - Time of Occurrence of Cmax | BIA 9-1067 | NA hours |
| Repaglinide | Tmax - Time of Occurrence of Cmax | Repaglinide | 0.50 hours |