Clinical trial NCT03633591: A Study Assessing the Safety and Pharmacokinetic Profile of Modified Release Formulations of Tolcapone
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Corino Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2018-08-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic Assessment: Time to maximum concentration (Tmax)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment: Maximum observed concentration (Cmax)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment: Area under the curve (AUC)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment: Plasma half-life (t1/2)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment: Relative bioavailability (Frel)
timeFrame: Pre-dose to 24 hours post-dose
Secondary outcomes:
measure: Pharmacokinetic Assessment of 3-O-Methyltolcapone: Time to maximum concentration (Tmax)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment of 3-O-Methyltolcapone: Maximum observed concentration (Cmax)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment of 3-O-Methyltolcapone: Area under the curve (AUC)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment of 3-O-Methyltolcapone: Plasma half-life (t1/2)
timeFrame: Pre-dose to 24 hours post-dose
measure: Pharmacokinetic Assessment of 3-O-Methyltolcapone: Relative Bioavailability (Frel)
timeFrame: Pre-dose to 24 hours post-dose
measure: Number of subjects reporting treatment-related Adverse Events (AEs)
timeFrame: Screening to 10 days following last dose
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Sciences
state: Nottingham
Study officials:
affiliation: Quotient Sciences
name: Litza McKenzie
role: PRINCIPAL_INVESTIGATOR
References: