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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: BIA 9-1067; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, F-35000
    • Biotrial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Principal Investigator: Nicolas Fauchoux, MD, Biotrial

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 18, 2012
• First Submitted That Met QC Criteria: January 26, 2012
• First Posted (Estimate): January 30, 2012

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: BIA 9-1067
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone; Entacapone
• Other Study ID Numbers: BIA-91067-101