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

Study Overview
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Brief Summary
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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.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Filgotinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |