A Single Oral Ascending Dose Study of BIA 9-1067 in Healthy Male Subjects

Study Overview
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Brief Summary
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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
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Single centre, randomised, double-blind, placebo-controlled study of single ascending doses in up to 8 sequential groups of 8 healthy young male subjects.

Official Title
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A Single Oral Ascending Dose Study to Investigate the Safety, Pharmacokinetics and Catechol-O-methyltransferase (COMT) Inhibition Profiles of BIA 9-1067 in Healthy Male Subjects

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: BIA 9-1067
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIA 9-1067 10 mg<br>BIA 9-1067 (Opicapone, OPC) - 10 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 25 mg<br>BIA 9-1067 (Opicapone, OPC) - 25 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 50 mg<br>BIA 9-1067 (Opicapone, OPC) - 50 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 100 mg<br>BIA 9-1067 (Opicapone, OPC) - 100 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 200 mg<br>BIA 9-1067 (Opicapone, OPC) - 200 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 400 mg<br>BIA 9-1067 (Opicapone, OPC) - 400 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 800 mg<br>BIA 9-1067 (Opicapone, OPC) - 800 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Experimental: BIA 9-1067 1200 mg<br>BIA 9-1067 (Opicapone, OPC) - 1200 mg | Drug: BIA 9-1067<br>* single ascending doses in up to 8 sequential groups of 8 healthy young male subjects<br>* Other names: Entacapone;|
| Placebo Comparator: Placebo<br>Placebo (PLC): single-dose | Drug: Placebo<br>* single-dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Safety was evaluated from the number of reported adverse events (AEs) | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - BIA 9-1067 | Cmax - maximum plasma concentration | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BIA 9-1067