Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Tenofovir Alafenamide (TAF) in Adults With Normal Hepatic Function and Adults With Severe Hepatic Impairment (NCT NCT02296853)
NCT ID: NCT02296853
Last Updated: 2020-12-09
Results Overview
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
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
Results posted on
2020-12-09
Participant Flow
Participants were enrolled at study sites in Germany, New Zealand, and the United States. The first participant was screened on 22 December 2014. The last study visit occurred on 17 April 2015.
28 participants were screened.
Participant milestones
| Measure |
Severe Hepatic Impairment Group
Participants with severe hepatic impairment received a single oral dose of tenofovir alafenamide (TAF) 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Pharmacokinetics of Tenofovir Alafenamide (TAF) in Adults With Normal Hepatic Function and Adults With Severe Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
55 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
56 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 1Population: Participants in the PK Analysis Set (consisted of all enrolled participants who received at least 1 dose of the study drug and had at least 1 non-missing PK concentration data for each respective analyte) with available data were analyzed.
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Outcome measures
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF
TAF
|
120.6 h*ng/mL
Standard Deviation 33.96
|
228.2 h*ng/mL
Standard Deviation 85.30
|
|
Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF
TFV
|
219.9 h*ng/mL
Standard Deviation 118.70
|
304.0 h*ng/mL
Standard Deviation 72.45
|
|
Pharmacokinetic (PK) Parameter: AUCinf of Tenofovir Alafenamide (TAF), Its Metabolite Tenofovir (TFV) and Free (Unbound) TAF
Free (unbound) TAF
|
42.8 h*ng/mL
Standard Deviation 11.76
|
46.5 h*ng/mL
Standard Deviation 17.78
|
PRIMARY outcome
Timeframe: 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 1Population: Participants in the PK Analysis Set were analyzed.
Cmax is defined as the maximum concentration of drug.
Outcome measures
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF
Free (unbound) TAF
|
29.9 ng/mL
Standard Deviation 17.36
|
36.2 ng/mL
Standard Deviation 18.38
|
|
PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF
TAF
|
79.6 ng/mL
Standard Deviation 39.31
|
176.0 ng/mL
Standard Deviation 79.77
|
|
PK Parameter: Cmax of TAF, Its Metabolite TFV and Free (Unbound) TAF
TFV
|
7.5 ng/mL
Standard Deviation 3.95
|
7.6 ng/mL
Standard Deviation 1.83
|
PRIMARY outcome
Timeframe: 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 1Population: Participants in the PK Analysis Set were analyzed.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Outcome measures
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF
TAF
|
113.1 h*ng/mL
Standard Deviation 30.85
|
225.7 h*ng/mL
Standard Deviation 85.09
|
|
PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF
TFV
|
184.2 h*ng/mL
Standard Deviation 99.86
|
256.7 h*ng/mL
Standard Deviation 59.91
|
|
PK Parameter: AUClast of TAF, Its Metabolite TFV and Free (Unbound) TAF
Free (unbound) TAF
|
41.7 h*ng/mL
Standard Deviation 11.17
|
46 h*ng/mL
Standard Deviation 17.75
|
SECONDARY outcome
Timeframe: Day 1 plus 30 daysPopulation: The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
|
40.0 percentage of participants
|
30.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 plus 30 daysPopulation: Participants in the Safety Analysis Set were analyzed.
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.
Outcome measures
| Measure |
Severe Hepatic Impairment Group
n=10 Participants
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 Participants
Participants with normal hepatic function received a single oral dose of TAF 25 mg on Day 1.
|
|---|---|---|
|
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
Grade 1
|
40.0 percentage of participants
|
30.0 percentage of participants
|
|
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
Grade 2
|
40.0 percentage of participants
|
30.0 percentage of participants
|
|
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
Grade 3
|
20.0 percentage of participants
|
10.0 percentage of participants
|
|
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
Grade 4
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
Severe Hepatic Impairment Group
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Matched Normal Hepatic Function Group
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Severe Hepatic Impairment Group
n=10 participants at risk
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 participants at risk
Participants with normal hepatic function received a single oral dose of TAF 25 mg of on Day 1.
|
|---|---|---|
|
Hepatobiliary disorders
Hepatic failure
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Severe Hepatic Impairment Group
n=10 participants at risk
Participants with severe hepatic impairment received a single oral dose of TAF 25 mg on Day 1.
|
Matched Normal Hepatic Function Group
n=10 participants at risk
Participants with normal hepatic function received a single oral dose of TAF 25 mg of on Day 1.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
20.0%
2/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
General disorders
Fatigue
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
20.0%
2/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
1/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 plus 30 days
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
Additional Information
Gilead Clinical Study Information Center
Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER