Parkinson
Conditions
Brief summary
Single-centre, open-label, randomised, three-part, two-way crossover study in 84 healthy volunteers. In each part, the study consisted of two consecutive single-dose treatment periods separated by a washout period of at least 14 days.
Interventions
DRUGBIA 9-1067 (clinical micronized, CM)
DRUGBIA 9-1067 (to-be-marketed, TBM)
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 before any study-specific screening procedure was performed; * Male or female subjects aged 18 to 45 years, inclusive; * Body mass index (BMI) between 18 and 30 kg/m2 inclusive; * 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 antibodies (HCV Ab) and anti-human immunodeficiency virus antibodies (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; * Able to participate, and willing to give written informed consent and comply with the study restrictions. * If female: * She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used 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 all the duration of the study; * She had a negative serum pregnancy test at screening and a negative urine pregnancy test at 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, or had a clinically relevant surgical history; * Had clinically relevant findings in laboratory tests, particularly any abnormality in the coagulation tests, or any abnormality in the liver function tests; * Had a history of relevant atopy or drug hypersensitivity; * Had a history of alcoholism and/or drug abuse; * Consumed more than 14 units of alcohol per week \[1 unit of alcohol = 280 mL beer (3-4°) = 100 mL wine (10-12°) = 30 mL spirits (40°)\]; * Had a significant infection or known inflammatory process on screening or admission to each treatment period; * Had 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 could affect the safety or other study assessments, in the Investigator's opinion; * Had previously received opicapone; * Had used any investigational drug or participated in any clinical trial within 90 days 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; * Were vegetarians, vegans or had medical dietary restrictions; * Could not communicate reliably with the Investigator; * Were unlikely to co-operate with the requirements of the study; * Were unwilling or unable to give written informed consent; If female: * She was pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax - Maximum Observed Plasma Concentration | before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose | Area Under the plasma concentration-time Curve from time 0 to the time of last quantifiable concentration |
| Tmax - Time of Occurrence of Cmax | before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 9-1067 5 mg Sequence 1 volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 15 |
| BIA 9-1067 25 mg Sequence 1 volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 14 |
| BIA 9-1067 50 mg Sequence 1 volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 14 |
| BIA 9-1067 5 mg Sequence 2 volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 14 |
| BIA 9-1067 25 mg Sequence 2 volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 14 |
| BIA 9-1067 50 mg Sequence 2 volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation
CM - clinical micronized TBM - to-be-marketed
BIA 9-1067 (clinical micronized, CM)
BIA 9-1067 (to-be-marketed, TBM) | 14 |
| Total | 85 |
Baseline characteristics
| Characteristic | BIA 9-1067 50 mg Sequence 1 | BIA 9-1067 5 mg Sequence 2 | BIA 9-1067 5 mg Sequence 1 | BIA 9-1067 25 mg Sequence 1 | BIA 9-1067 25 mg Sequence 2 | BIA 9-1067 50 mg Sequence 2 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 15 Participants | 14 Participants | 14 Participants | 14 Participants | 85 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 29 | 3 / 28 | 6 / 28 | 3 / 28 | 1 / 28 | 3 / 28 |
| serious Total, serious adverse events | 0 / 29 | 0 / 28 | 1 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Cmax - Maximum Observed Plasma Concentration
Time frame: before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 5 mg CM | Cmax - Maximum Observed Plasma Concentration | 107.3 ng/mL | Standard Deviation 55.7 |
| BIA 9-1067 5 mg TBM | Cmax - Maximum Observed Plasma Concentration | 95.5 ng/mL | Standard Deviation 37.8 |
| BIA 9-1067 25 mg CM | Cmax - Maximum Observed Plasma Concentration | 424.5 ng/mL | Standard Deviation 155.7 |
| BIA 9-1067 25 mg TBM | Cmax - Maximum Observed Plasma Concentration | 471.0 ng/mL | Standard Deviation 206.9 |
| BIA 9-1067 50 mg CM | Cmax - Maximum Observed Plasma Concentration | 756.2 ng/mL | Standard Deviation 302.4 |
| BIA 9-1067 50 mg TBM | Cmax - Maximum Observed Plasma Concentration | 802.9 ng/mL | Standard Deviation 363 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067
Area Under the plasma concentration-time Curve from time 0 to the time of last quantifiable concentration
Time frame: before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 5 mg CM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 196.8 ng.h/mL | Standard Deviation 128.5 |
| BIA 9-1067 5 mg TBM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 197.7 ng.h/mL | Standard Deviation 89.7 |
| BIA 9-1067 25 mg CM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 1137 ng.h/mL | Standard Deviation 413.8 |
| BIA 9-1067 25 mg TBM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 1270 ng.h/mL | Standard Deviation 515.5 |
| BIA 9-1067 50 mg CM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 2043 ng.h/mL | Standard Deviation 1032 |
| BIA 9-1067 50 mg TBM | AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 | 2161 ng.h/mL | Standard Deviation 1110 |
Secondary
Tmax - Time of Occurrence of Cmax
Time frame: before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIA 9-1067 5 mg CM | Tmax - Time of Occurrence of Cmax | 2.00 hours |
| BIA 9-1067 5 mg TBM | Tmax - Time of Occurrence of Cmax | 1.00 hours |
| BIA 9-1067 25 mg CM | Tmax - Time of Occurrence of Cmax | 2.00 hours |
| BIA 9-1067 25 mg TBM | Tmax - Time of Occurrence of Cmax | 2.00 hours |
| BIA 9-1067 50 mg CM | Tmax - Time of Occurrence of Cmax | 2.00 hours |
| BIA 9-1067 50 mg TBM | Tmax - Time of Occurrence of Cmax | 2.00 hours |