Parkinson Disease
Conditions
Brief summary
Single-centre, open-label, randomised, two-way crossover study in 28 healthy volunteers. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 14 days or more.
Detailed description
Single-centre, open-label, randomised, two-way crossover study in 28 healthy volunteers. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 14 days or more. A total of twenty-eight (28) healthy volunteers received a single dose of 50 mg OPC, orally.
Interventions
DRUGBIA 9-1067 non-micronized
DRUGBIA 9-1067 micronized
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
* A signed and dated informed consent form (ICF) before any study-specific screening procedure was performed, * 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 electrocardiogram (ECG), * Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies and anti-human immunodeficiency virus (HIV) antibodies at screening, * Clinical laboratory test results clinically acceptable at screening and on D-1 of each treatment period, * Negative screen for alcohol and drugs of abuse at screening and on D-1 of each treatment period, * Non-smokers or ex-smokers for at least 3 months, * Volunteer able to participate, and willing to give written informed consent and comply with the study restrictions, If female: * Was not of childbearing potential by reason of surgery or, if of childbearing potential, uses an effective non-hormonal 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 the entire duration of the study, * Negative serum pregnancy test at screening and a negative urine pregnancy test on D-1 of each treatment period.
Exclusion criteria
* Any 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, or had a clinically relevant surgical history, * Any clinically relevant abnormality in the coagulation tests, * Any clinically relevant abnormality in the liver function tests, * History of relevant atopy or drug hypersensitivity, * History of alcoholism and/or drug abuse, * Current consumption of more than 14 units of alcohol per week \[1 unit of alcohol = 280 mL beer (3-4°) = 100 mL wine (10-12°) = 30 mL spirits (40°)\], * Any significant infection or known inflammatory process on screening or admission to each treatment period, * Any acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period, * Use of medicines within 2 weeks of admission to first period that could affect the subject's safety or other study assessments, in the investigator's opinion, * Previously received opicapone, * Involvement in other clinical trials of any type within 90 days prior to screening, * Participation in more than 2 clinical trials within the 12 months prior to screening, * Blood donation or received any blood transfusion or any blood products within the 3 months prior to screening, * Vegetarian, vegan or had medical dietary restrictions, * Subject not able to 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: * Pregnant or breast-feeding, * If of childbearing potential, a positive serum pregnancy test, * Volunteer who did not use an accepted effective contraceptive method or used oral contraceptives,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Concentration | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose. | Maximum observed plasma concentration of BIA 9-1067 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose. | AUC0-t - Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration of BIA 9-1067 |
| Tmax - Time of Occurrence of Cmax of BIA 9-1067 | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose. | tmax - time of occurrence of maximum observed plasma concentration of BIA 9-1067 |
| AUC0-inf - Area Under the Plasma Concentration-time Curve From Time 0 to the Infinity | before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose. | AUC0-inf - Area under the plasma concentration-time curve from time 0 to the infinity. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 9-1067 Non-micronized - Micronized Each subject was orally administered with 50 mg OPC non-micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC micronized
BIA 9-1067 non-micronized
BIA 9-1067 micronized | 14 |
| BIA 9-1067 Micronized - Non-micronized Each subject was orally administered 50 mg OPC micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC non-micronized
BIA 9-1067 non-micronized
BIA 9-1067 micronized | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | BIA 9-1067 Non-micronized - Micronized | BIA 9-1067 Micronized - Non-micronized | 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 | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 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 | 2 / 28 | 1 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Concentration
Maximum observed plasma concentration of BIA 9-1067
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 Non-micronized | Cmax - Maximum Observed Plasma Concentration | 327.8 ng/mL | Standard Deviation 129.6 |
| BIA 9-1067 Micronized | Cmax - Maximum Observed Plasma Concentration | 750.1 ng/mL | Standard Deviation 184.1 |
Secondary
AUC0-inf - Area Under the Plasma Concentration-time Curve From Time 0 to the Infinity
AUC0-inf - Area under the plasma concentration-time curve from time 0 to the infinity.
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 Non-micronized | AUC0-inf - Area Under the Plasma Concentration-time Curve From Time 0 to the Infinity | 1327.0 ng.h/mL | Standard Deviation 562 |
| BIA 9-1067 Micronized | AUC0-inf - Area Under the Plasma Concentration-time Curve From Time 0 to the Infinity | 2324.1 ng.h/mL | Standard Deviation 781.8 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration
AUC0-t - Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration of BIA 9-1067
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 Non-micronized | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration | 1152.8 ng.h/mL | Standard Deviation 537.5 |
| BIA 9-1067 Micronized | AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration | 2296.5 ng.h/mL | Standard Deviation 778.2 |
Secondary
Tmax - Time of Occurrence of Cmax of BIA 9-1067
tmax - time of occurrence of maximum observed plasma concentration of BIA 9-1067
Time frame: before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BIA 9-1067 Non-micronized | Tmax - Time of Occurrence of Cmax of BIA 9-1067 | 2.50 hours |
| BIA 9-1067 Micronized | Tmax - Time of Occurrence of Cmax of BIA 9-1067 | 2.00 hours |