Bioavailability and Bioequivalence Study of Two Different Sources of Opicapone

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the bioavailability and the bioequivalence between two active pharmaceutical ingredient (API) sources of opicapone (OPC) at two different dosage strengths (25 mg and 50 mg) after a single oral dose administration under fasting conditions in healthy male and female subjects.

Detailed Description
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Single-center, fasted, open-label, randomized, gender-balanced, single-dose, laboratory blinded, two-periods, two-sequence, crossover study in 2 groups of subjects. In Group 1, subjects will receive randomly in Period 1 and 2, either a single 25 mg dose of OPC approved formulation [AF] or a single 25 mg dose of OPC formulation to be submitted for approval [NF]. In Group 2, subjects will receive randomly on Period 1 and 2, either a single 50 mg dose of OPC (AF), or a single 50 mg dose of OPC (NF

Official Title
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A Comparative, Randomized, Open-label, Fasted, Single-dose, 2-way Crossover Bioavailability and Bioequivalence Study of Two Different Sources of Opicapone 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: Subjects signed and dated the ICF before any study-specific screening procedure. Male and female subjects, between 18 and 55 years of age (inclusive). BMI between 18 and 30 kg/m² inclusive. Subjects have a supine blood pressure (after at least 5 minutes rest in supine position) of: systolic blood pressure ≥90 and <140 mmHg, diastolic blood pressure ≥50 and <90 mmHg and a pulse rate ≥50 and ≤90 bpm (beats per minute). Subjects have no clinically relevant abnormal ECG parameters: heart rate ≥50 and ≤90 bpm, PR interval ≤ 220 milliseconds (ms), QRS duration ≤120 ms, QTcB interval ≤450 ms. No clinically relevant pathological findings in the 12-lead ECG. Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (HCVab) and anti-HIV antibodies (HIV-1 and HIV-2 Ab) at screening. Clinical laboratory test results clinically acceptable at screening and admission to each treatment period. Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period. Non-smokers or ex-smokers for at least 3 months. If female, the pregnancy test at screening and at admission to each treatment period must be negative. Female subjects are of non-childbearing potential (postmenopausal [no menses for at least 1 year] or surgically sterile [tubal ligation, hysterectomy or bilateral oophorectomy]). Female subjects of childbearing potential must use an acceptable method of non-hormonal method of contraception and should be informed of the potential risks associated with becoming pregnant while enrolled within a clinical investigation. Acceptable methods for this study are: intrauterine device, condom or occlusive cap (diaphragm or cervical or vault caps) with spermicide, true abstinence or vasectomized male partner, provided that he is the sole partner of that subject). Able to participate, and willing to give written ICF and comply with the study restrictions. Exclusion Criteria: Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders, or have a clinically relevant surgical history. Subjects with clinically relevant neurologic or psychiatric illness. Subjects with a history of symptomatic orthostatic hypotension. Subjects with clinically relevant allergy (except for untreated, asymptomatic, seasonal allergies at time of dosing) as judged by the Principal investigator. Subjects with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption Subjects with clinically significant findings in laboratory tests, particularly any abnormality in the coagulation tests, or any abnormality in the kidney function tests especially creatinine above 1.2 x upper limit of normal (ULN) and/or liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST],) above 1.25 x ULN confirmed by two repeated measurements, when it is checked during the screening laboratory tests. Subjects with a history of relevant atopy or drug hypersensitivity. Subjects with a history of alcoholism and/or drug abuse. Consumption of more than 14 units of alcohol per week [1 unit of alcohol = 280 ml beer (3-4°) = 100 ml wine (10-12°) = 30 ml spirits (40°)]. Subjects with a significant infection or known inflammatory process at screening or admission to each treatment period. Subjects with acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or admission to each treatment period. Use of medicines within 2 weeks prior to the planned first drug administration that may affect the safety or other study assessments, in the investigator's opinion (excluding single use of up to 1000 mg paracetamol). Use of any investigational drug or participation in any clinical trial within 30 days or 10 half-life, whatever is longer, prior to the planned first drug administration. Donation or receipt of any blood or blood products within the 2 months prior to the planned first drug administration. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Group 1 - 25 mg OPC<br>In Group 1, subjects will receive randomly in Period 1 and 2, either a single 25 mg dose of OPC [AF] or a single 25 mg dose of OPC [NF]. Treatments will be administered in the fasting state, the subjects having fasted for at least 10 hours | Drug: Opicapone (OPC)<br>* Test treatment: 25 mg or 50 mg of OPC hard capsule (new API source NF) Reference treatment: Ongentys® 25 mg or 50 mg of OPC hard capsule (current API source - AF).<br>* Other names: BIA 9-1067;|
| Experimental: Group 2 - 50 mg OPC<br>In Group 2, subjects will receive randomly on Period 1 and 2, either a single 50 mg dose of OPC [AF], or a single 50 mg dose of OPC [NF]. Treatments will be administered in the fasting state, the subjects having fasted for at least 10 hours | Drug: Opicapone (OPC)<br>* Test treatment: 25 mg or 50 mg of OPC hard capsule (new API source NF) Reference treatment: Ongentys® 25 mg or 50 mg of OPC hard capsule (current API source - AF).<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 drug concentration. (Cmax) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Time of the maximum drug concentration (tmax) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Area under the plasma concentration-time curve calculated from time zero (time of drug administration) to the latest time point with a quantifiable plasma concentration (AUC0-t) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent terminal elimination rate constant - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent terminal elimination half-life (t1/2) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent total body clearance (CL/F) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent volume of distribution (V/F) - Period 1 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Maximum observed drug concentration (Cmax) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Time of the maximum drug concentration (tmax) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Area under the plasma concentration-time curve calculated from time zero (time of drug administration) to the latest time point with a quantifiable plasma concentration (AUC0-t) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent terminal elimination rate constant - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent terminal elimination half-life (t1/2) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent total body clearance (CL/F) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose | 
| Apparent volume of distribution (V/F) - Period 2 | Pharmacokinetic variables | pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose |