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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B Virus
• Intervention / Treatment: Drug: TAF

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, D-81241
• New Zealand
  • Auckland
    • Gratton, Auckland, New Zealand, 1142
• United States
  • Florida
    • Miami, Florida, United States, 33014
    • Orlando, Florida, United States, 32809
  • Texas
    • San Antonio, Texas, United States, 78215

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2014
• Primary Completion (Actual): April 17, 2015
• Study Completion (Actual): April 17, 2015

Study Registration Dates

• First Submitted: November 18, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): December 9, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Severe Hepatic Impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: GS-US-320-1615; 2014-004426-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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