Parkinson Disease
Conditions
Keywords
BIA 9-1067
Brief summary
The purpose of this study was to investigate the safety, tolerability, pharmacokinetics and catechol-O-methyltransferase (COMT) activity of BIA 9-1067 in healthy male subjects after single oral ascending doses.
Detailed description
Single centre, randomised, double-blind, placebo-controlled study of single ascending doses in up to 8 sequential groups of 8 healthy young male subjects.
Interventions
DRUGBIA 9-1067
single ascending doses in up to 8 sequential groups of 8 healthy young male subjects
DRUGPlacebo
single-dose
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
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. * Aged between 18 and 45 years, inclusive. * Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead ECG. * Non-smoker or smoker of fewer than 10 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
Exclusion criteria
* Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease. * Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day 1. * History of drug abuse within 1 year before study day 1. * History of alcoholism within 1 year before day 1. Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g * Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies. * Positive findings of urine drug screen (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA \[3,4-methylenedioxy-methamphetamine; ecstasy\]). * History of any clinically important drug allergy. * Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration. * Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study day 1. * Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen \[paracetamol\], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before IMP administration. * Donation of blood (i.e. 450 mL) within 60 days before study day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | 7 weeks | Safety was evaluated from the number of reported adverse events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - BIA 9-1067 | pre-dose then post-dose. Hour 0.25, 0.5, 0,75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 , 60 and 72 hours post dose | Cmax - maximum plasma concentration |
| Time to Cmax (Tmax) | pre-dose then post-dose. Hour 0.25, 0.5, 0,75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 , 60 and 72 hours post dose | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 9-1067 10 mg BIA 9-1067 (Opicapone, OPC) - 10 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 25 mg BIA 9-1067 (Opicapone, OPC) - 25 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 50 mg BIA 9-1067 (Opicapone, OPC) - 50 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 100 mg BIA 9-1067 (Opicapone, OPC) - 100 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 200 mg BIA 9-1067 (Opicapone, OPC) - 200 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 400 mg BIA 9-1067 (Opicapone, OPC) - 400 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 800 mg BIA 9-1067 (Opicapone, OPC) - 800 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| BIA 9-1067 1200 mg BIA 9-1067 (Opicapone, OPC) - 1200 mg
BIA 9-1067: single ascending doses in up to 8 sequential groups of 8 healthy young male subjects | 6 |
| Placebo Placebo (PLC): single-dose
Placebo: single-dose | 16 |
| Total | 64 |
Baseline characteristics
| Characteristic | BIA 9-1067 10 mg | BIA 9-1067 25 mg | BIA 9-1067 50 mg | BIA 9-1067 100 mg | BIA 9-1067 200 mg | BIA 9-1067 400 mg | BIA 9-1067 800 mg | BIA 9-1067 1200 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 16 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 16 Participants | 64 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 2 / 6 | 0 / 6 | 1 / 6 | 1 / 6 | 0 / 6 | 1 / 6 | 2 / 16 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 16 |
Outcome results
Primary
Adverse Events (AEs)
Safety was evaluated from the number of reported adverse events (AEs)
Time frame: 7 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIA 9-1067 10 mg | Adverse Events (AEs) | 0 Number of Adverse Events |
| BIA 9-1067 25 mg | Adverse Events (AEs) | 0 Number of Adverse Events |
| BIA 9-1067 50 mg | Adverse Events (AEs) | 2 Number of Adverse Events |
| BIA 9-1067 100 mg | Adverse Events (AEs) | 0 Number of Adverse Events |
| BIA 9-1067 200 mg | Adverse Events (AEs) | 1 Number of Adverse Events |
| BIA 9-1067 400 mg | Adverse Events (AEs) | 1 Number of Adverse Events |
| BIA 9-1067 800 mg | Adverse Events (AEs) | 0 Number of Adverse Events |
| BIA 9-1067 1200 mg | Adverse Events (AEs) | 1 Number of Adverse Events |
| Placebo | Adverse Events (AEs) | 4 Number of Adverse Events |
Secondary
Cmax - BIA 9-1067
Cmax - maximum plasma concentration
Time frame: pre-dose then post-dose. Hour 0.25, 0.5, 0,75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 , 60 and 72 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 10 mg | Cmax - BIA 9-1067 | 130.7 ng/mL | Standard Deviation 68 |
| BIA 9-1067 25 mg | Cmax - BIA 9-1067 | 308.5 ng/mL | Standard Deviation 128.1 |
| BIA 9-1067 50 mg | Cmax - BIA 9-1067 | 522.2 ng/mL | Standard Deviation 186.7 |
| BIA 9-1067 100 mg | Cmax - BIA 9-1067 | 927.2 ng/mL | Standard Deviation 378.9 |
| BIA 9-1067 200 mg | Cmax - BIA 9-1067 | 1287.5 ng/mL | Standard Deviation 585.6 |
| BIA 9-1067 400 mg | Cmax - BIA 9-1067 | 2013.3 ng/mL | Standard Deviation 608.7 |
| BIA 9-1067 800 mg | Cmax - BIA 9-1067 | 2786.7 ng/mL | Standard Deviation 1335.9 |
| BIA 9-1067 1200 mg | Cmax - BIA 9-1067 | 4883.3 ng/mL | Standard Deviation 1501.5 |
Secondary
Time to Cmax (Tmax)
Time frame: pre-dose then post-dose. Hour 0.25, 0.5, 0,75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 , 60 and 72 hours post dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIA 9-1067 10 mg | Time to Cmax (Tmax) | 2.5 hours |
| BIA 9-1067 25 mg | Time to Cmax (Tmax) | 1.5 hours |
| BIA 9-1067 50 mg | Time to Cmax (Tmax) | 3.5 hours |
| BIA 9-1067 100 mg | Time to Cmax (Tmax) | 1.8 hours |
| BIA 9-1067 200 mg | Time to Cmax (Tmax) | 2.0 hours |
| BIA 9-1067 400 mg | Time to Cmax (Tmax) | 2.0 hours |
| BIA 9-1067 800 mg | Time to Cmax (Tmax) | 2.5 hours |
| BIA 9-1067 1200 mg | Time to Cmax (Tmax) | 1.5 hours |