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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Tozadenant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults, Liver Disease