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

A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of Filgotinib in Subjects With Impaired Hepatic Function

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Filgotinib

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

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81241
    • APEX GmbH
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Ltd.
• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Hepatic Impairment; Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.	Drug: Filgotinib; 100 mg tablet administered orally; Other Names: GS-6034; GLPG0634
Experimental: Severe Hepatic Impairment; Participants with severe hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.	Drug: Filgotinib; 100 mg tablet administered orally; Other Names: GS-6034; GLPG0634
Experimental: Mild Hepatic Impairment; Participants with mild hepatic impairment and matched healthy controls will receive a single dose of filgotinib on Day 1.	Drug: Filgotinib; 100 mg tablet administered orally; Other Names: GS-6034; GLPG0634

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events		Day 1 up to Day 31
Percentage of Participants Who Experienced Graded Laboratory Abnormalities	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.	Day 1 up to Day 31

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Galapagos NV

Publications and helpful links

General Publications

• Anderson K, Zheng H, Medzihradsky O, et al. THU0117 PHARMACOKINETICS AND SHORT-TERM SAFETY OF FILGOTINIB, A SELECTIVE JANUS KINASE 1 INHIBITOR, IN SUBJECTS WITH MODERATE HEPATIC IMPAIRMENT. Annals of the Rheumatic Diseases. 2019;78:331.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Actual): August 9, 2018
• Study Completion (Actual): August 9, 2018

Study Registration Dates

• First Submitted: January 25, 2018
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: GS-US-417-4048; 2017-000156-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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