Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Filgotinib in Participants With Impaired Hepatic Function (NCT NCT03417778)
NCT ID: NCT03417778
Last Updated: 2021-01-15
Results Overview
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1
Results posted on
2021-01-15
Participant Flow
Participants were enrolled at study sites in Germany, New Zealand, and United States. The first participant was screened on 03 April 2018. The last study visit occurred on 09 August 2018.
38 participants were screened. Per protocol, participants in adaptive Cohort 2 (severe hepatic impairment) and Cohort 3 (mild hepatic impairment) were not enrolled following review of safety and pharmacokinetic (PK) data from participants in Cohort 1 (moderate hepatic impairment).
Participant milestones
| Measure |
Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
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 Filgotinib in Participants With Impaired Hepatic Function
Baseline characteristics by cohort
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
62 years
STANDARD_DEVIATION 5.3 • n=7 Participants
|
61 years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 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
New Zealand
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1Population: The PK Analysis Set included all enrolled participants who received at least 1 dose of filgotinib and had at least 1 nonmissing postdose concentration value of filgotinib or its primary metabolite GS-829845 reported by the PK laboratory.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: AUClast of Filgotinib
|
2389.3 h*ng/mL
Standard Deviation 530.85
|
1981.9 h*ng/mL
Standard Deviation 995.78
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 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. GS-829845 is the primary metabolite of filgotinib.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
PK Parameter: AUClast of GS-829845
|
32466.8 h*ng/mL
Standard Deviation 10898.85
|
31412.6 h*ng/mL
Standard Deviation 13758.34
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
PK Parameter: AUCinf of Filgotinib
|
2417.0 h*ng/mL
Standard Deviation 533.74
|
1995.9 h*ng/mL
Standard Deviation 997.88
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
AUCinf is defined as the concentration of drug extrapolated to infinite time. GS-829845 is the primary metabolite of filgotinib.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
PK Parameter: AUCinf of GS-829845
|
33296.5 h*ng/mL
Standard Deviation 11568.33
|
32060.0 h*ng/mL
Standard Deviation 14329.57
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Cmax is defined as the maximum observed concentration of drug.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
PK Parameter: Cmax of Filgotinib
|
722.6 ng/mL
Standard Deviation 293.24
|
802.2 ng/mL
Standard Deviation 485.98
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Cmax is defined as the maximum observed concentration of drug. GS-829845 is the primary metabolite of filgotinib.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
PK Parameter: Cmax of GS-829845
|
972.5 ng/mL
Standard Deviation 256.09
|
1122.6 ng/mL
Standard Deviation 447.45
|
SECONDARY outcome
Timeframe: Day 1 up to Day 31Population: The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
|
30.0 percentage of participants
|
10.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 31Population: 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. The most severe graded abnormality from all tests was counted for each participant.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 Participants
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Any Laboratory Abnormality
|
90.0 percentage of participants
|
70.0 percentage of participants
|
|
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Grade 3 or 4 Laboratory Abnormalities
|
60.0 percentage of participants
|
0.0 percentage of participants
|
Adverse Events
Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Healthy Control
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate Hepatic Impairment
n=10 participants at risk
Participants with moderate hepatic impairment received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
Healthy Control
n=10 participants at risk
Matched healthy control participants received a single dose of filgotinib 100 mg administered orally on Day 1, in a fasted state.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
General disorders
Chest discomfort
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Day 1 up to Day 31
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 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
10.0%
1/10 • Day 1 up to Day 31
The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 31
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