Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Tozadenant

A Two-Part, Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Tozadenant

This is a two-part, open label, single-dose study that will evaluate the PK of tozadenant in subjects with different degrees of hepatic impairment to the PK of a single-dose of tozadenant in healthy subjects.

Study Overview

• Status: Terminated
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Tozadenant

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32809-3017
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects must fulfill the following to participate:

• Subject has given his/her written informed consent on an IEC or IRB approved consent form.
• Subject understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol.
• Be either male or female 18 years old
• Have a BMI ≥ 18.5 and ≤ 40.0 kg/m2 at screening
• Is a continuous non-smoker or a smoker who will consume up to 10 cigarettes/day
• Child bearing females should be sexually inactive (abstinent) prior to dosing
• Females subjects of non childbearing potential must have undergone one of the following sterilization or be postmenopausal

Subjects with mild, moderate, or severe hepatic impairment must:

• Have a medical history consistent with a diagnosis of hepatic impairment.
• Have a diagnosis of chronic (> 6 months), stable hepatic insufficiency

Healthy subjects must be:

• Medically healthy with no significant medical history

Exclusion Criteria:

Subjects must not be enrolled in the study if they:

• Previously participated in any study with tozadenant
• Has orthostatic hypotension, history or symptoms of cardiovascular disease, or hypertensive crisis.
• Currently participating in or has participated in another study and received drug (active or placebo)
• Have a known diagnosis of malignant melanoma
• Have a current episode of major depression
• Has a recent history of suicide attempt
• Has any other condition or clinically significant abnormal findings on the physical or neurological examination, psychiatric and medical history
• Had surgery or any medical condition within 6 months
• Unable to refrain from or anticipates the use of any drugs, vitamins, natural or herbal supplements
• Subject is currently lactating or pregnant or planning to become pregnant.
• Recent donation of blood, plasma or significant blood loss
• Has positive test for ethanol or drugs of abuse or a history of chronic alcohol or drug abuse
• Clinically significant medical history
• Positive results hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) for Healthy Volunteers only.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Subjects; Study dose of 120 mg	Drug: Tozadenant; Two 60 mg tablets for a total single study dose of 120 mg
Experimental: Mild Hepatic Impairment; Study dose of 120 mg	Drug: Tozadenant; Two 60 mg tablets for a total single study dose of 120 mg
Experimental: Moderate Hepatic Impairment; Study dose of 120 mg	Drug: Tozadenant; Two 60 mg tablets for a total single study dose of 120 mg
Experimental: Severe Hepatic Impairment; Up to a maximum study dose of 120 mg	Drug: Tozadenant; Two 60 mg tablets for a total single study dose of 120 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the pharmacokinetics (PK) [area under the time-concentration curve] of a single-dose of tozadenant in subjects with hepatic impairment to healthy subjects.	To evaluate the pharmacokinetics (PK) [area under the time-concentration curve] of a single-dose of tozadenant in subjects with hepatic impairment compared to the PK of a single-dose of tozadenant in healthy subjects.	up to 12 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects with hepatic impairment will be evaluated for safety assessments (adverse events and treatment-related adverse events) by physical examinations.	To evaluate the safety and tolerability of a single-dose of tozadenant in subjects with hepatic impairment by physical examinations, vital sign measurements and Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire.	up to 12 days

Collaborators and Investigators

• Sponsor: Biotie Therapies Inc.
• Collaborators: Acorda Therapeutics
• Investigators: Principal Investigator: Richard Preston, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: June 30, 2017
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: January 2, 2018
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Adults; Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: TOZ-CL11

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: Yes
• Studies a U.S. FDA-regulated device product: No