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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Tolcapone; Drug: Tolcapone Modified Release Prototype; Drug: Tolcapone Divided Dose; Drug: Tolcapone Modified Release Prototype

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Modified Release Prototypes of Tolcapone

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Corino Therapeutics, Inc.
• Collaborators: Quotient Sciences
• Investigators: Principal Investigator: Litza McKenzie, Quotient Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2018
• Primary Completion (Actual): October 22, 2018
• Study Completion (Actual): October 22, 2018

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Tolcapone
• Other Study ID Numbers: TOLC101MR; 2017-003070-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No