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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03417778
• Other study ID #: GS-US-417-4048
• Secondary ID: 2017-000156-25
• Status: Completed
• Phase: Phase 1
• Start date: April 3, 2018
• Est. completion date: August 9, 2018

Study information

• Verified date: December 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 9, 2018
• Est. primary completion date: August 9, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Filgotinib
100 mg tablet administered orally

Locations

Country	Name	City	State
Germany	APEX GmbH	Munich
New Zealand	Auckland Clinical Studies Ltd.	Grafton	Auckland
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Galapagos NV

Countries where clinical trial is conducted

United States,  Germany,  New Zealand, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Percentage of Participants Who Experienced Treatment-Emergent Adverse Events		Day 1 up to Day 31
Secondary	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