Effect of Paracetamol on Opicapone Pharmacokinetics in Healthy Volunteers

Single-centre, open-label, randomised, two-way cross-over study consisting of 2 periods separated by a washout period of 14 days or more.

Study Overview

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

Detailed Description

Single-centre, open-label, randomised, two-way cross-over study consisting of 2 periods separated by a washout period of 14 days or more. In one period, subjects received three single-doses of 1 g paracetamol separated by 6 hours and 1.5 hours after the last paracetamol dose a single-dose of 50 mg OPC was administered.In the other period, a single-dose of 50 mg OPC was administered alone.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects who are able and willing to give written informed consent.
• Male or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19.0 and 30.0 kg/m2, inclusive.
• Subjects who are healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Subjects who have negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
• Subjects who have clinical laboratory test results clinically acceptable at screening and admission to each treatment period.
• Subjects who have a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.
• Subjects who are non-smokers or ex-smokers for at least 3 months.
• (If female) She is not of childbearing potential by reason of surgery or, if of childbearing potential, she 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 is the sole partner of that subject) for all the duration of the study.
• (If female) She has a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 of each treatment period.

Exclusion Criteria:

• Subjects who have 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.
• Subjects who have a clinically relevant surgical history.
• Subjects who have any clinically relevant abnormality in the coagulation tests.
• Subjects who have any clinically relevant abnormality in the liver function tests (a case-by-case decision for any abnormality must be discussed with the Sponsor before inclusion).
• Subjects who have a history of relevant atopy or drug hypersensitivity, particularly to paracetamol or any COMT inhibitor.
• Subjects who have a history of alcoholism or drug abuse.
• Subjects who consume more than 14 units of alcohol a week.
• Subjects who have a significant infection or known inflammatory process at screening or admission to each treatment period.
• Subjects who have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period.
• Subjects who have received paracetamol within 2 weeks of admission to the first period.
• Subjects who have used any other medicines within 2 weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion.
• Subjects who have previously received OPC.
• Subjects who have used any investigational drug or participated in any clinical trial within 90 days prior to screening.
• Subjects who have participated in more than 2 clinical trials within the 12 months prior to screening.
• Subjects who have donated or received any blood or blood products within the 3 months prior to screening.
• Subjects who are vegetarians, vegans or have medical dietary restrictions.
• Subjects who cannot communicate reliably with the investigator.
• Subjects who are unlikely to co-operate with the requirements of the study.
• Subjects who are unwilling or unable to give written informed consent.
• (If female) She is pregnant or breast-feeding.
• (If female) She is of childbearing potential and she does not use an approved effective contraceptive method or she uses oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1 OPC + Paracetamol; Period 2 OPC; Period 1 BIA 9-1067 (Opicapone, OPC) + Paracetamol; Period 2 BIA 9-1067 (Opicapone, OPC)	Drug: BIA 9-1067; BIA 9-1067 50 mg; Other Names: OPC, Opicapone; Drug: Paracetamol; Paracetamol 1g; Other Names: acetaminophen
Experimental: Period 1 OPC; Period 2 OPC+ Paracetamol; Period 1 BIA 9-1067 (Opicapone, OPC) Period 2 BIA 9-1067 (Opicapone, OPC) + Paracetamol;	Drug: BIA 9-1067; BIA 9-1067 50 mg; Other Names: OPC, Opicapone; Drug: Paracetamol; Paracetamol 1g; Other Names: acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Plasma Concentration	Cmax - Maximum plasma concentration of opicapone on Day 12 following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration	before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax - Time of Occurrence of Cmax	Tmax - time of occurrence of Cmax following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration.	before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification	AUC0-t - area under the plasma concentration-time curve (AUC) from time zero to the last sampling time following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration	before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity.	AUC0-∞ - AUC from time 0 to infinity following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration.	before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 28, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 2, 2014

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Acetaminophen; Opicapone
• Other Study ID Numbers: BIA-91067-125