Study to Evaluate the Pharmacokinetics of Filgotinib in Participants With Impaired Hepatic Function

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Filgotinib

• Registration Number: NCT03417778
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to evaluate the pharmacokinetics (PK) of filgotinib and its metabolite, GS-829845, in participants with varying degrees of impaired hepatic function relative to matched, healthy controls.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-25
• Study First Submitted QC: 2018-01-25
• Study First Posted: 2018-01-31
• Study Start: 2018-04-03
• Primary Completion: 2018-08-09
• Study Completion: 2018-08-09
• Status Verified: 2020-12
• Results First Submitted: 2020-12-21
• Results First Submitted QC: 2020-12-21
• Last Update Submitted: 2020-12-21
• Results First Posted: 2021-01-15
• Last Update Posted: 2021-01-15

Recruitment & Eligibility

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

Inclusion Criteria

• Eligible individuals will be male and nonpregnant, nonlactating females, aged 18 to 70 years (inclusive), body mass index (BMI) between 18 and 36 kg/m^2 (inclusive), with either impaired hepatic function or normal hepatic function.

• Individuals will be current nonsmokers (no use of tobacco, nicotine-containing, or tetrahydrocannabinol [THC]-containing products within the last 14 days).

• Individuals with hepatic impairment will be categorized by the Child-Pugh-Turcotte (CPT) classification system indicating hepatic impairment as follows:

  • Class A (mild): CPT score 5-6
  • Class B (moderate): CPT score 7-9
  • Class C (severe): CPT score 10-15

• Hepatic impairment must have been stable during the 3 months (90 days) prior to study drug. Each individual in the control group will be matched to a individual with impaired hepatic function by age (± 10 years), gender, and body mass index (± 15%).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe Hepatic Impairment	Filgotinib	Participants with severe hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.
Mild Hepatic Impairment	Filgotinib	Participants with mild hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.
Moderate Hepatic Impairment	Filgotinib	Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: AUClast of Filgotinib	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	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUClast of GS-829845	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	AUClast is defined as the concentration of drug from time zero to the last observable concentration. GS-829845 is the primary metabolite of filgotinib.
PK Parameter: AUCinf of Filgotinib	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	AUCinf is defined as the concentration of drug extrapolated to infinite time.
PK Parameter: AUCinf of GS-829845	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	AUCinf is defined as the concentration of drug extrapolated to infinite time. GS-829845 is the primary metabolite of filgotinib.
PK Parameter: Cmax of Filgotinib	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	Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Cmax of GS-829845	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	Cmax is defined as the maximum observed concentration of drug. GS-829845 is the primary metabolite of filgotinib.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events	Day 1 up to Day 31
Percentage of Participants Who Experienced Graded Laboratory Abnormalities	Day 1 up to Day 31	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.

Trial Locations

Locations (4)

Auckland Clinical Studies Ltd.; 🇳🇿 Grafton, Auckland, New Zealand

Clinical Pharmacology of Miami; 🇺🇸 Miami, Florida, United States

APEX GmbH; 🇩🇪 Munich, Germany

American Research Corporation at the Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States