Study to Evaluate the Pharmacokinetics of Tenofovir Alafenamide (TAF) in Adults With Normal Hepatic Function and Adults With Severe Hepatic Impairment

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the single-dose pharmacokinetics of tenofovir alafenamide (TAF) and its metabolite tenofovir (TFV) in participants with normal hepatic function and in participants with severe hepatic impairment.

Official Title
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A Phase 1, Open-Label, Parallel-Group, Single Dose Study to Evaluate the Pharmacokinetics of Tenofovir Alafenamide (TAF) in Subjects With Normal Hepatic Function and Subjects With Severe Hepatic Impairment

Conditions
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Hepatitis B Virus

Intervention / Treatment
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* Drug: TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Screening laboratory parameters within defined thresholds Creatinine clearance must be ≥ 60 mL/min Key Exclusion Criteria: Females who are pregnant or nursing or males who have a pregnant partner Infection with hepatitis B virus (HBV) or HIV History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with participant treatment and/or adherence to the protocol NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Severe Hepatic Impairment Group<br>Participants with severe hepatic impairment will receive a single oral dose of TAF 25 mg on Day 1. | Drug: TAF<br>* 25 mg tablet administered orally<br>|
| Active Comparator: Matched Normal Hepatic Function Group<br>Participants with normal hepatic function will receive a single oral dose of TAF 25 mg on Day 1. | Drug: TAF<br>* 25 mg tablet administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 | 
| PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF | Cmax is defined as the maximum concentration of drug. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 | 
| PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Predose (≤5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours postdose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs are events that meet one of the following criteria: any AEs with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. | Day 1 plus 30 days | 
| Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. These were graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening. The most severe graded abnormality from all tests was counted for each participant. | Day 1 plus 30 days | 

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