A Study Assessing the Safety and Pharmacokinetic Profile of Modified Release Formulations of Tolcapone

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetic profiles of tolcapone in healthy subjects after administration of one or two oral doses of multiple modified release prototype formulations.

Official Title
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A Phase 1, Single-Part, 6-Period, Sequential, Non-Randomized, Open-Label Study Designed to Evaluate the Pharmacokinetic Profile of Tolcapone Following Administration of Modified Release Prototype Formulations and an Experimental Divided Dose Regimen in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Tolcapone
* Drug: Tolcapone Modified Release Prototype
* Drug: Tolcapone Divided Dose
* Drug: Tolcapone Modified Release Prototype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or non-pregnant, non-lactating healthy females Age 18 to 65 years of age at the time of signing informed consent Body mass index (BMI) of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator Must be willing and able to communicate and participate in the whole study Must provide written informed consent Must agree to use an adequate method of contraception Exclusion Criteria: Subjects who have received any IMP in a clinical research study within the previous 3 months prior to first dose. Subjects who are study site employees, or immediate family members of a study site or sponsor employee. Subjects who have previously been enrolled in this study. History of any drug or alcohol abuse in the past 2 years. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Females of childbearing potential who are pregnant or lactating Subjects who do not have suitable veins for multiple venepunctures / cannulation as assessed by the investigator at screening Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator Hemoglobin below the lower limit of normal ALT or AST outside the normal reference range at screening or admission. Confirmed positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of clinically significant cardiovascular, neurological, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder, as judged by the investigator Subjects with a history of cholecystectomy or gall stones Serious adverse reaction or serious hypersensitivity to any drug, the formulation excipients, or lactose intolerance Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Donation or loss of greater than 400 mL of blood within the previous 3 months Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days before IMP administration. Contraindication for Tasmar® Failure to satisfy the investigator of fitness to participate for any other reason NOTE: Other inclusion/exclusion criteria may apply, per protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modified Release Prototypes of Tolcapone<br> | Drug: Tolcapone<br>* Multiple doses of tolcapone tablets in the fasted state<br>* Other names: Tasmar;Drug: Tolcapone Modified Release Prototype<br>* A single dose of tolcapone modified release prototype in the fasted state<br>Drug: Tolcapone Divided Dose<br>* Tolcapone (suspension) in equal divided doses in the fasted state<br>Drug: Tolcapone Modified Release Prototype<br>* A single dose of tolcapone modified release prototype (optionally two doses or fed state of prior MR prototype)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessment: Time to maximum concentration (Tmax) | Time to maximum concentration (Tmax) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment: Maximum observed concentration (Cmax) | Maximum observed concentration (Cmax) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment: Area under the curve (AUC) | Area under the curve (AUC) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment: Plasma half-life (t1/2) | Plasma half-life (t1/2) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment: Relative bioavailability (Frel) | Relative bioavailability (Frel) | Pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessment of 3-O-Methyltolcapone: Time to maximum concentration (Tmax) | Time to maximum concentration (Tmax) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment of 3-O-Methyltolcapone: Maximum observed concentration (Cmax) | Maximum observed concentration (Cmax) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment of 3-O-Methyltolcapone: Area under the curve (AUC) | Area under the curve (AUC) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment of 3-O-Methyltolcapone: Plasma half-life (t1/2) | Plasma half-life (t1/2) | Pre-dose to 24 hours post-dose | 
| Pharmacokinetic Assessment of 3-O-Methyltolcapone: Relative Bioavailability (Frel) | Relative Bioavailability (Frel) | Pre-dose to 24 hours post-dose | 
| Number of subjects reporting treatment-related Adverse Events (AEs) | Abnormalities in safety laboratory tests, vital signs, electrocardiogram, physical examination that meet the protocol definition will be captured as AEs | Screening to 10 days following last dose |