PK Study of T-817 in Subjects With Hepatic Impairment

Study Overview
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Brief Summary
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The primary objective is to determine the single-dose pharmacokinetics (PK) of T-817 and T-817M5 (metabolite of T-817) in subjects with mild, moderate or severe hepatic impairment compared to matched healthy control subjects. The secondary objective is to determine the safety and tolerability of single-dose T -817MA (Maleate salt of T-817) in subjects with mild, moderate or severe hepatic impairment.

Official Title
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A Phase 1, Two-Part, Open-Label, Parallel-Cohort, Single-Dose Study to Determine the Pharmacokinetics of T-817MA in Adult Subjects With Hepatic Impairment and in Healthy Adult Subjects

Conditions
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Healthy, Hepatic Impairment

Intervention / Treatment
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* Drug: T-817MA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For subjects with mild, moderate or severe hepatic impairment Adult male or female, 18 - 75 years of age Must weigh at least 50 kg and have a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m2 Have mild, moderate or severe defined by Child-Pugh classification hepatic impairment For Matched Healthy Control Subjects Healthy adult male or female subjects will be matched 1:1 to a specific subject in the mild, moderate, or severe hepatic impairment cohort based upon age, weight, gender, and smoking status Exclusion Criteria: Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI. History or presence of hypersensitivity or idiosyncratic reaction to the study drug, related compounds, or inactive ingredients. Female subjects who are pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1:T-817MA<br>Mild hepatic impairment subjects | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|
| Experimental: Cohort 2:T-817MA<br>Healthy subjects matched to subjects in Cohort 1 | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|
| Experimental: Cohort 3:T-817MA<br>Moderate hepatic impairment subjects | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|
| Experimental: Cohort 4:T-817MA<br>Healthy subjects matched to subjects in Cohort 3 | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|
| Experimental: Cohort 5 :T-817MA<br>Severe hepatic impairment subjects | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|
| Experimental: Cohort 6:T-817MA<br>Healthy subjects matched to subjects in Cohort 5 | Drug: T-817MA<br>* A single oral dose of 448 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations |  | 8 days | 
| Area under the plasma concentration time curve (AUC) |  | 8 days | 
| Maximum observed plasma concentration (Cmax) |  | 8 days | 
| Time to reach the maximum observed plasma concentration (tmax) |  | 8 days | 
| Apparent terminal elimination rate constant |  | 8 days | 
| Apparent terminal elimination half-life (t½) |  | 8 days | 
| Apparent total plasma clearance of unbound drug after oral (extravascular) administration (CL/F) |  | 8 days | 
| Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vd/F) |  | 8 days | 
| Metabolite to parent ratio (MPR) |  | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events |  | 8days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment