Effect of Food on Opicapone

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of food on the catechol-O-Methyltransferase (COMT) activity after repeated doses of opicapone (OPC, development code BIA 9-1067) in healthy subjects and to characterize the effects of food on the pharmacokinetics (PK) and tolerability of OPC after repeated doses.

Detailed Description
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Single-centre, open-label, single-arm study in 28 healthy subjects. Subjects received a single-dose of 50 mg OPC once-daily (QD) in the evening for 12 days. On Day 1 (D1), 50 mg OPC was orally administered in the evening (reference hour for all other administrations) after a minimum of 6 hours fast. From D2 to D8 subjects were in ambulatory and received 50 mg OPC once-daily (evening administration after 2 hours fast). On D9, 50 mg OPC was orally administered in the evening after a minimum of 6 hours fast. On D10, 50 mg OPC was orally administered in the evening, thirty minutes after the start of a moderate meal (with a previous 6 hours fast). On D11 and D12 subjects received the last doses of 50 mg OPC (evening administration after 2 hours fast).

Official Title
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Effect of Food on Opicapone Bioavailability and Pharmacodynamics in Healthy Subjects

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Opicapone (OPC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent and to comply with the study restrictions. Male or female subjects aged between 18 and 45 years, inclusive. Body mass index (BMI) between 19 and 30 kg/m2, inclusive. Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. Negative tests for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab at screening. Clinical laboratory test results clinically acceptable at screening and admission. Negative screen for alcohol and drugs of abuse at screening and admission. Non-smokers or ex-smokers for at least 3 months. If female: 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. Negative serum pregnancy test at screening and a negative urine pregnancy test on admission. Exclusion Criteria: 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. Clinically relevant surgical history. Clinically relevant abnormality in the coagulation tests. Clinically relevant abnormality in the liver function tests. History of relevant atopy or drug hypersensitivity, particularly to any COMT inhibitor. History of alcoholism or drug abuse. Consume more than 14 units of alcohol a week. Significant infection or known inflammatory process at screening or admission. Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission. Used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion. Previously received OPC. Used any investigational drug or participated in any clinical trial within 90 days prior to screening. Participated in more than 2 clinical trials within the 12 months prior to screening. Donated or received any blood or blood products within the 3 months prior to screening. Vegetarians, vegans or have medical dietary restrictions. Cannot communicate reliably with the investigator. Unlikely to co-operate with the requirements of the study. If female: Pregnant or breast-feeding. Of childbearing potential and not used 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg OPC<br>Subjects received 50 mg OPC once-daily in the evening for 12 days. On D9 subjects were to receive 50 mg OPC in the evening after a minimum 6 hours fast. On D10 subjects were to receive the QD dose of 50 mg OPC thirty minutes after the start of moderate meal (with a previous 6 hours fast) | Drug: Opicapone (OPC)<br>* 50 mg OPC capsules; oral route<br>* Other names: BIA 9-1067;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed effect on COMT activity (Emax) - Day 9 (fasted state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Time to occurrence of Emax (tEmax) - Day 9 (fasted state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Area under the effect-time curve (AUEC) - Day 9 (fasted state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Maximum observed effect on COMT activity (Emax) - Day 10 (fed state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Time to occurrence of Emax (tEmax) - Day 10 (fed state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Area under the effect-time curve (AUEC) - Day 10 (fed state) | Pharmacodynamic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) - Day 9 (fasted state) | Pharmacokinetic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Time of occurrence of Cmax (tmax) - Day 9 (fasted state) | Pharmacokinetic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Maximum observed plasma concentration (Cmax) - Day 10 (fed state) | Pharmacokinetic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | 
| Time of occurrence of Cmax (tmax) - Day 10 (fed state) | Pharmacokinetic parameters for opicapone | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose |