Effect of Paracetamol on Opicapone Pharmacokinetics in Healthy Volunteers

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

Detailed Description
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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.

Official Title
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Effect of Paracetamol on Opicapone Pharmacokinetics in Healthy Volunteers

Conditions
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Parkinson's Disease

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


Participation Criteria
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Eligibility Criteria
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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.

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

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |