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

• Tolcapone (Drug), also known as Tasmar: Multiple doses of tolcapone tablets in the fasted state
• Tolcapone Modified Release Prototype (Drug): A single dose of tolcapone modified release prototype in the fasted state
• Tolcapone Divided Dose (Drug): Tolcapone (suspension) in equal divided doses in the fasted state
• Tolcapone Modified Release Prototype (Drug): A single dose of tolcapone modified release prototype (optionally two doses or fed state of prior MR prototype)

Primary outcomes

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

Secondary outcomes

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

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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

• Litza McKenzie, Principal investigator, Quotient Sciences

NIH grants: 2017