PK Study of T-817 in Subjects With Hepatic Impairment

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: T-817MA

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States
      • University of Miami
    • Orlando, Florida, United States
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For subjects with mild, moderate or severe hepatic impairment

1. Adult male or female, 18 - 75 years of age
2. Must weigh at least 50 kg and have a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m2
3. 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:

1. 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.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
3. History or presence of hypersensitivity or idiosyncratic reaction to the study drug, related compounds, or inactive ingredients.
4. Female subjects who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: FUJIFILM Toyama Chemical Co., Ltd.
• Collaborators: Celerion
• Investigators: Principal Investigator: Richard Preston, M.D., University of Miami; Principal Investigator: Thomas Marbury, M.D., Orlando Clinical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): November 24, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Hepatic Impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: T817MAUS113

Drug and device information, study documents

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