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

Phase 1

Completed

• Conditions: Hepatitis B Virus
• Interventions: Drug: TAF

• Registration Number: NCT02296853
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-18
• Study First Submitted QC: 2014-11-19
• Study First Posted: 2014-11-20
• Study Start: 2014-12-22
• Primary Completion: 2015-04-17
• Study Completion: 2015-04-17
• Status Verified: 2020-11
• Results First Submitted: 2020-11-12
• Results First Submitted QC: 2020-11-12
• Last Update Submitted: 2020-11-12
• Results First Posted: 2020-12-09
• Last Update Posted: 2020-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe Hepatic Impairment Group	TAF	Participants with severe hepatic impairment will receive a single oral dose of TAF 25 mg on Day 1.
Matched Normal Hepatic Function Group	TAF	Participants with normal hepatic function will receive a single oral dose of TAF 25 mg on Day 1.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF	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	AUCinf is defined as the concentration of drug extrapolated to infinite time.
PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF	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	Cmax is defined as the maximum concentration of drug.
PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF	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	AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Day 1 plus 30 days	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.
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities	Day 1 plus 30 days	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.