A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of Filgotinib in Subjects With Impaired Hepatic Function
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of 
Filgotinib in Subjects with Impaired Hepatic Function
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND No.:
EudraCT No.:
IND 115510
2017-000156-25
Indication:
Rheumatoid Arthritis
Protocol ID:
GS-US-417-4048
Gilead Medical Monitor
Name:
Telephone:
Fax:
Cell:
Protocol Version/Date:
Original:
19 December 2017
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol.
You will not disclose any of the information to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
PPD
PPD
PPD
PPD

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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEXT FIGURES ......................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................10
1.
INTRODUCTION ..............................................................................................................................................13
1.1.
Background ............................................................................................................................................13
1.2.
Filgotinib................................................................................................................................................13
1.2.1.
General Information .............................................................................................................13
1.2.2.
Preclinical Pharmacology, Pharmacokinetics and Toxicology.............................................14
1.2.3.
Additional Clinical Studies of Filgotinib .............................................................................15
1.3.
Rationale for This Study ........................................................................................................................15
1.4.
Rationale for the Dose Selection............................................................................................................16
1.5.
Risk/Benefit Assessment for the Study..................................................................................................17
1.6.
Compliance ............................................................................................................................................17
2.
OBJECTIVES.....................................................................................................................................................18
3.
STUDY DESIGN................................................................................................................................................19
3.1.
Study Design..........................................................................................................................................19
3.1.1.
Cohorts 1 – 3 ........................................................................................................................20
3.2.
Study Drug Administration ....................................................................................................................21
3.3.
Clinic Confinement ................................................................................................................................21
3.4.
Pharmacokinetic Assessments................................................................................................................21
3.4.1.
Plasma Pharmacokinetic Collection.....................................................................................21
3.5.
Samples for Optional Future Research...................................................................................................21
3.6.
Safety Assessments ................................................................................................................................22
3.7.
End of Study...........................................................................................................................................22
4.
SUBJECT POPULATION..................................................................................................................................23
4.1.
Number of Subjects and Subject Selection ............................................................................................23
4.2.
Inclusion Criteria....................................................................................................................................23
4.2.1.
All Subjects ..........................................................................................................................23
4.2.2.
Subjects with Impaired Hepatic Function ............................................................................24
4.2.3.
Healthy Matched Control Subjects.......................................................................................25
4.3.
Exclusion Criteria...................................................................................................................................26
4.3.1.
All Subjects ..........................................................................................................................26
4.3.2.
Subjects with Impaired Hepatic Function ............................................................................27
4.3.3.
Healthy Matched Control Subjects.......................................................................................29
5.
STUDY DRUGS.................................................................................................................................................30
5.1.
Enrollment..............................................................................................................................................30
5.2.
Description and Handling of Filgotinib..................................................................................................30
5.2.1.
Formulation..........................................................................................................................30
5.2.2.
Packaging and Labeling .......................................................................................................30
5.2.3.
Storage and Handling...........................................................................................................31
5.3.
Dosage and Administration of Study Drug ............................................................................................31
5.4.
Fasting and Meals ..................................................................................................................................31
5.5.
Dispensing, Accountability, and Disposal or Return of Study Drug......................................................31

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5.5.1.
Study Drug Return or Disposal ............................................................................................32
5.6.
Concomitant Medications and Other Protocol Restrictions ...................................................................32
5.6.1.
Concomitant Medications.....................................................................................................32
5.6.2.
Other Protocol Restrictions ..................................................................................................33
6.
STUDY ASSESSMENTS...................................................................................................................................35
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................35
6.2.
Pretreatment Assessments......................................................................................................................38
6.2.1.
Screening Visit .....................................................................................................................38
6.2.2.
Admission Assessments .......................................................................................................38
6.3.
Check-in Assessments............................................................................................................................39
6.4.
Treatment Assessments..........................................................................................................................39
6.5.
Posttreatment Assessments ....................................................................................................................39
6.6.
Assessments for Premature Discontinuation from Study.......................................................................39
6.7.
Study Stopping Criteria..........................................................................................................................39
6.8.
Pharmacokinetic Assessments................................................................................................................39
6.9.
Safety Assessments ................................................................................................................................40
6.9.1.
Electrocardiogram Assessment ............................................................................................40
6.9.2.
Physical Examination...........................................................................................................40
6.9.3.
Vital Signs............................................................................................................................40
6.9.4.
Body Mass Index..................................................................................................................41
6.9.5.
Clinical Laboratory Tests/Assessments................................................................................41
6.9.6.
Creatinine Clearance ............................................................................................................41
6.9.7.
Adverse Events/Concomitant Medications/Protocol Restrictions........................................42
6.10.
Sample Storage.......................................................................................................................................42
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................43
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................43
7.1.1.
Adverse Events.....................................................................................................................43
7.1.2.
Serious Adverse Events........................................................................................................43
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................44
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................44
7.2.2.
Assessment of Severity ........................................................................................................44
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................45
7.3.1.
Requirements for Collection Prior to Study Drug Initiation.................................................45
7.4.
Gilead Reporting Requirements.............................................................................................................47
7.5.
Clinical Laboratory Abnormalities.........................................................................................................47
7.6.
Toxicity Management ............................................................................................................................48
7.7.
Special Situations Reports......................................................................................................................48
7.7.1.
Definitions of Special Situations..........................................................................................48
7.7.2.
Instructions for Reporting Special Situations.......................................................................49
8.
STATISTICAL CONSIDERATIONS................................................................................................................51
8.1.
Analysis Objectives and Endpoints........................................................................................................51
8.1.1.
Analysis Objectives..............................................................................................................51
8.1.2.
Primary Endpoint .................................................................................................................51
8.1.3.
Secondary Endpoint .............................................................................................................51
8.2.
Analysis Conventions.............................................................................................................................51
8.2.1.
Analysis Sets ........................................................................................................................51
8.3.
Data Handling Conventions ...................................................................................................................52
8.4.
Demographic Data and Baseline Characteristics ...................................................................................52
8.5.
Interim Analysis.....................................................................................................................................52
8.6.
Safety Analysis.......................................................................................................................................52

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8.6.1.
Extent of Exposure...............................................................................................................52
8.6.2.
Adverse Events.....................................................................................................................52
8.6.3.
Laboratory Evaluations ........................................................................................................53
8.6.4.
Other Safety Evaluations......................................................................................................53
8.7.
Pharmacokinetic Analysis......................................................................................................................53
8.8.
Sample Size............................................................................................................................................53
9.
RESPONSIBILITIES..........................................................................................................................................54
9.1.
Investigator Responsibilities ..................................................................................................................54
9.1.1.
Good Clinical Practice..........................................................................................................54
9.1.2.
Institutional Review Board/Independent Ethics Committee Review and 
Approval...............................................................................................................................54
9.1.3.
Informed Consent.................................................................................................................55
9.1.4.
Confidentiality......................................................................................................................55
9.1.5.
Study Files and Retention of Records ..................................................................................55
9.1.6.
Case Report Forms...............................................................................................................56
9.1.7.
Study Drug Accountability and Return ................................................................................57
9.1.8.
Inspections............................................................................................................................57
9.1.9.
Protocol Compliance............................................................................................................57
9.2.
Sponsor Responsibilities ........................................................................................................................58
9.2.1.
Protocol Modifications.........................................................................................................58
9.2.2.
Study Report and Publications .............................................................................................58
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................58
9.3.1.
Payment Reporting...............................................................................................................58
9.3.2.
Access to Information for Monitoring..................................................................................59
9.3.3.
Access to Information for Auditing or Inspections ..............................................................59
9.3.4.
Study Discontinuation..........................................................................................................59
10.
REFERENCES ...................................................................................................................................................60
11.
APPENDICES ....................................................................................................................................................61
Appendix 1.
Investigator Signature Page....................................................................................................62
Appendix 2.
Management of Clinical and Laboratory Adverse Events......................................................63
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................64
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03....................................68
LIST OF IN-TEXT TABLES
Table 6-1.
Schedule of Assessments........................................................................................................36
Table 7-1.
Grading of Adverse Event Severity........................................................................................45
LIST OF IN-TEXT FIGURES
Figure 3-1.
High-Level Study Schema......................................................................................................20
Figure 3-2.
Study Schema.........................................................................................................................20

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title:
A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of 
Filgotinib in Subjects with Impaired Hepatic Function
IND Number:
EudraCT Number:
IND 115510
2017-000156-25
Study Centers 
Planned:
Multiple centers in the United States, Germany, and New Zealand
Objectives:
The primary objective of this study is as follows:

To evaluate the pharmacokinetics (PK) of filgotinib and its 
metabolite, GS-829845, in subjects with impaired hepatic 
function relative to matched, healthy controls
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of filgotinib in subjects 
with normal and impaired hepatic function
Study Design:
Phase 1, open-label, adaptive, single-dose study
Number of Subjects 
Planned:
Up to 60 subjects enrolled for up to 48 evaluable:

Cohort 1 (Moderate Hepatic Impairment): 20 subjects 
(10 subjects with moderate hepatic impairment and 10 healthy 
matched controls for 8 evaluable subjects per group).

Adaptive Cohort 2 (Severe Hepatic Impairment): 20 subjects 
(10 subjects with severe hepatic impairment and 10 healthy 
matched controls for 8 evaluable subjects per group).

Adaptive Cohort 3 (Mild Hepatic Impairment): 20 subjects 
(10 with mild hepatic impairment and 10 matched healthy 
controls for 8 evaluable subjects per group).
A subject with normal hepatic function may serve as a matched 
control across cohorts but may only serve as a matched control to 
one hepatically impaired subject within a cohort.
Subjects in adaptive Cohort 2 (Severe Hepatic Impairment) and 
Cohort 3 (Mild Hepatic Impairment) may be enrolled after the review 
by Sponsor of safety and PK data from subjects in Cohort 1
(Moderate Hepatic Impairment).

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Target Population:
Male and nonpregnant, nonlactating female subjects, aged 18 to 
70 years (inclusive), with varying degrees of hepatic impairment and 
matched healthy controls. 
Subjects with hepatic impairment will be enrolled based upon the 
Child-Pugh-Turcotte (CPT) classification system indicating moderate 
hepatic impairment (CPT Class B; Cohort 1), severe hepatic 
impairment (CPT Class C; Cohort 2), or mild hepatic impairment 
(CPT Class A; Cohort 3). The control group will consist of matched 
healthy subjects with normal hepatic function.
Duration of Dosing:
1 day
Study Duration:
Up to 15 days (not including screening window)
Diagnosis and Main 
Eligibility Criteria:
Eligible subjects will be male and nonpregnant, nonlactating female 
subjects, aged 18 to 70 years (inclusive), body mass index (BMI) 
between 18 and 36 kg/m2 (inclusive), with either impaired hepatic 
function or normal hepatic function. Subjects will be current 
nonsmokers (no use of tobacco, nicotine-containing, or 
tetrahydrocannabinol (THC)-containing products within the last 14 
days). 
Subjects with hepatic impairment will be categorized by the 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 subject in the control group will 
be matched to a subject with impaired hepatic function by age 
(± 10 years), gender, and body mass index (± 15%).
Study Procedures/
Frequency:
Following completion of Screening and Day -1 assessments, eligible 
subjects will receive a single oral dose of 100 mg filgotinib 
(1 x 100 mg tablet) on Day 1, in fasting state.
Dosing in subjects with normal hepatic function will begin after a 
matched subject with hepatic impairment has completed all Day 1 PK 
assessments.
Study Visits and Confinement
Following Screening and admission assessments, eligible subjects 
will be confined to the study center beginning Day -1 until the 
completion of assessments on Day 6. Subjects will return for an 
in-clinic follow-up (FU) visit on Day 15 (± 1 day).

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Study Drug Administration
Study drug will be administered on Day 1 with 240 mL of water 
following an overnight fast (no food or drinks except for water) for at 
least 10 hours. Subjects will continue to fast until after collection of 
the 4-hour blood sample, relative to study drug dosing. Additionally, 
subjects will be restricted from water consumption 1 hour before until 
2 hours after dosing, except for the 240 mL given with the study 
treatment. A standardized meal may be provided to subjects after 
collection of the 4-hour blood draw.
Pharmacokinetic Assessments
Intensive PK sampling will occur relative to dosing of filgotinib at the 
following time points:
Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 5, 6, 8, 
12, 18, 24, 36, 48, 72, 96, and 120 hours postdose
A blood sample for PK analysis will be collected at the Early 
Termination (ET) visit (if applicable) and may be analyzed.
Plasma concentrations of filgotinib and its metabolite (GS-829845) 
will be measured and PK parameters determined. Plasma 
concentrations of other metabolites may be determined and PK 
explored.
Protein binding of filgotinib and its major metabolite (GS-829845) 
will be assessed at their Tmax time point(s) as well as at another later 
time point.
Safety Assessments
Complete Physical Exam: Screening and the FU visit or the ET visit 
(if applicable)
Symptom-driven Physical Exam: Days -1, 1, and every day during 
confinement (as needed based on reported signs and symptoms)
Vital Signs (blood pressure, pulse, respiration rate, and 
temperature): Screening, Days -1, 1, 3, 6, and the FU or the ET visit 
(if applicable)
Height: Screening
Weight: Screening and Day -1
Clinical Laboratory Tests (hematology, blood chemistry including 
coagulation, and urinalysis): Screening, Days -1, 1, 6, and the FU or 
the ET visit (if applicable)
Urine Drug, Cotinine, and Alcohol Assessments: Screening, Day -1 
and the FU or the ET visit (if applicable)

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12-lead electrocardiogram (ECG): Screening, Days -1, 1 (2 hours 
post dose), 6, and the FU or ET visit (if applicable)
Serum Pregnancy Test (women of childbearing potential only): 
Screening, Days -1, 6 and the FU or the ET visit (if applicable)
Serology Test (HBV, HCV, HIV): Screening 
α-fetoprotein Test: Screening
Assessment of adverse events (AE) and concomitant medications will 
continue throughout the study.  All clinical AEs and clinically 
significant laboratory abnormalities will be managed according to 
uniform guidelines detailed in protocol Appendix 3
Protocol-Specific Stopping Rules
If ≥ 2 subjects in any cohort experience the same or similar Grade 3 
or Grade 4 treatment-emergent AE or confirmed laboratory 
abnormality that is not attributable to obvious alternative explanation 
(hematuria occurring in a menstruating female, creatine kinase [CK] 
elevation after strenuous exercise, or triglyceride elevation that is 
non-fasting, etc), a review of all safety data generated in subjects 
dosed to date will be initiated. The decision as to whether and how to 
proceed with further enrollment will be determined based on the 
safety review.
Test Product, Dose, 
and Mode of 
Administration:
A single dose of 100 mg filgotinib (1 x 100 mg tablet), in a fasted 
state.
Reference Therapy, 
Dose, and Mode of 
Administration:
Not applicable
Criteria for 
Evaluation:
Safety:
Safety will be assessed during the study through the reporting of AEs, 
and by clinical laboratory tests, physical examinations, vital signs, 
and ECGs at various time points during the study.
Efficacy:
Not applicable.
Pharmacokinetics:
The following plasma PK parameters of filgotinib and its metabolite 
(GS-829845) will be calculated, as appropriate: Cmax, Tmax, Clast, Tlast, 
λz, AUClast, AUCinf, %AUCexp, t½, CL/F, and Vz/F.

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Statistical Methods:
Pharmacokinetics:
Plasma PK parameters for filgotinib and GS-829845 will be listed and 
summarized by hepatic function group (normal or CPT Class A, B, or 
C) using descriptive statistics (eg, sample size, arithmetic mean, 
geometric mean, % coefficient of variation [CV], standard deviation
[SD], median, minimum, and maximum). 
An analysis of variance appropriate for a parallel design will be fit to 
the natural logarithm-transformed PK parameters (AUClast, AUCinf, 
and Cmax) for filgotinib and GS-829845. The 90% confidence 
intervals (CIs) will be constructed for the geometric least-squares 
mean (GLSM) ratio of PK parameters for filgotinib and GS-829845 
in groups of subjects with hepatic impairment versus matched 
controls.
Protein binding of filgotinib and GS-829845 at their Tmax and another 
later time point will be summarized by hepatic function group using 
descriptive statistics.
Safety:
Safety data will be listed by subject and summarized by hepatic
function group (normal or CPT Class A, B, or C) and frequency of 
event/abnormality or descriptive statistical summaries, as appropriate.
Sample Size:
With 16 (8 per group) evaluable subjects, the estimated two-sided 
90% CI of the geometric least-square mean (GLSM) ratio of test vs 
reference groups, with regards to PK parameters (AUC and Cmax) 
would be within (50%, 200%) with over 95% probability, if the 
estimated GLSM ratio were 1.0. This is assuming the SDs for PK 
parameters between subjects within each group is no more than 0.347
(or 0.203) for the natural logarithm-transformed PK parameters for 
filgotinib (or GS-829845). Such assumptions are supported by PK 
data from a prior Gilead study of filgotinib (GS-US-417-3900) with 
100 mg dose in healthy volunteers. 
An overage of 2 subjects per group will be enrolled in order to 
accommodate subject drop-outs, so a total sample size of 20 subjects 
(10 per group) for each cohort will be required.
This study will be conducted in accordance with the guidelines of Good Clinical Practices
(GCPs) including archiving of essential documents.

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
λz
terminal elimination rate constant, estimated by linear regression of the terminal 
elimination phase of the log concentration versus time curve of the drug
%AUCexp
percentage of AUC extrapolated between AUClast and AUCinf
C 
degrees Celsius
F
degrees Fahrenheit
AE
adverse event
ALT
alanine aminotransferase (previously serum glutamic pyruvic transaminase
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AUCinf
area under the concentration versus time curve extrapolated to infinite time, 
calculated as AUClast + (Clast/λz)
AUClast
area under the concentration versus time curve from time zero to the last quantifiable
concentration
BMI
body mass index
BUN
blood urea nitrogen
CBC
complete blood count
CD
Crohn’s disease
CES
carboxylesterases
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CL/F
apparent oral clearance after administration of the drug:
CL/F = Dose/AUCinf, where “Dose” is the dose of the drug
Clast
last observed quantifiable concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
CNS
central nervous system
CPK
creatine phosphokinase
CRF
case report form
CV
coefficient of variation
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EMA
European Medicines Agency
EudraCT
European Clinical Trials Database
ET
early termination
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
FU
follow-up

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GCP
Good Clinical Practice
GI
gastrointestinal
Gilead
Gilead Sciences, Inc.
GLP
Galapagos
GLSM
geometric least-squares mean
HBV
hepatitis B virus
HBcAb
hepatitis B virus core antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDL
high-density lipoprotein
HIV, HIV-1, HIV-2
human immunodeficiency virus, type 1, type 2
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
ICF
informed consent form
ICH
International Conference on Harmonization (of Technical Requirements for 
Registration of Pharmaceuticals for Human Use)
IEC
independent ethics committee
IND
investigational new drug (application)
IRB
institutional review board
IUD
intrauterine device
JAK
janus kinases
LDL
low-density lipoprotein
LLOQ
lower limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NDA
new drug application
PK
pharmacokinetic(s)
PT
prothrombin time
PTT
partial thromboplastin time
PVE
Pharmacovigilance & Epidemiology
QT
electrocardiographic interval between the beginning of the Q wave and termination of 
the T wave, representing the time for both ventricular depolarization and 
repolarization to occur
RA
rheumatoid arthritis
RBC
red blood cell
SADR
serious adverse drug reaction
SAE
serious adverse event 
SD
standard deviation
SOC
system organ class
SOP
standard operating procedure
STAT
signal transduction and activator of transcription

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SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
THC
tetrahydrocannabinol
Tlast
time (observed time point) of Clast
Tmax
the time (observed time point) of Cmax
TYK
tyrosine kinases
UC
ulcerative colitis
UGT
uridine disphosphate glucuronosyltransferases
ULN
upper limit of normal
US, USA
United States, United States of America
Vz/F
apparent volume of distribution of the drug

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1.
INTRODUCTION
1.1.
Background
Over the last decade, changes in rheumatoid arthritis (RA) treatment strategies, accompanied by 
advances in drug development and the addition of targeted biological therapies, have greatly 
improved the outcomes for subjects with RA. Despite these developments, therapeutic 
challenges remain. The current conventional and biological disease-modifying anti-rheumatic 
drugs are ineffective or produce only partial responses in some subjects and are associated with 
significant safety and tolerability concerns. There is an unmet medical need for simple, orally 
administered therapies with novel mechanisms of action that effectively improve the disease 
course while being safe and well tolerated.
Janus kinases (JAKs) are intracellular cytoplasmic tyrosine kinases (TYKs) that transduce 
cytokine signaling from membrane receptors to the nucleus of cells. JAK/ signal transduction 
and activator of transcription (STAT) signaling pathways are evolutionarily conserved and 
ubiquitous in animals and are activated by a variety of cytokines, growth factors, and other 
chemical messengers. Dysregulation of the JAK/STAT functionality is implicated in the 
pathogenesis of multiple diseases, including immuno-inflammatory diseases. Janus kinase 
inhibitors block the signaling of various cytokines, growth factors and hormones, including the 
pro-inflammatory cytokine interleukin (IL)-6. Four different types of JAKs are known which 
(co-)interact with different sets of membrane receptors: JAK1, JAK2, JAK3 and TYK2. Janus 
kinase plays a critical role in innate and adaptive immunity and hematopoiesis. The etiology of 
multiple inflammatory and autoimmune conditions may involve a combination of genetic 
predisposition, environmental factors, and ultimately a pathogenic inflammatory state.  This 
culminates in a loss of self-tolerance and expansion of T-cells that ultimately secrete 
pro-inflammatory cytokines, which activate and signal other cells of the immune system 
(eg, macrophages, natural killer cells, and neutrophils) that infiltrate targeted tissue {Clark 2014}. 
Inhibition of JAK/STAT signaling is a therapeutic option for a range of inflammatory conditions 
including RA and inflammatory bowel disease (IBD), two conditions with high and rising 
prevalence and significant unmet medical needs.
1.2.
Filgotinib
1.2.1.
General Information
Filgotinib (GS-6034, formerly GLPG0634) is a potent and selective oral inhibitor of JAK1 being 
developed by Gilead Sciences, Inc. (Gilead) and Galapagos (GLP) NV. Janus kinase 1 is 
believed to play an integral part in the pathogenesis of various autoimmune diseases, due its role 
in inflammatory cytokine signaling.  

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For further information on filgotinib refer to the Investigator’s Brochure (IB), including 
information on the following:

Nonclinical pharmacokinetic (PK) and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience
1.2.2.
Preclinical Pharmacology, Pharmacokinetics and Toxicology
Filgotinib is a highly selective, adenosine triphosphate -competitive inhibitor of JAK1. In 
cellular assays, it inhibits JAK/STAT-driven processes with half maximal inhibitory 
concentration (IC50) values from 179 nM upwards. In human whole blood assays, filgotinib 
exhibits approximately 30-fold selectivity over JAK2. Filgotinib demonstrated significant 
efficacy in the rat collagen-induced arthritis model as well as in the mouse dextran sulphate 
sodium -induced colitis model. Filgotinib’s metabolite, GS-829845, exhibits a similar JAK1 
selectivity profile, but is approximately 10 to 20-fold less potent than filgotinib.
Filgotinib demonstrates good oral bioavailability in all nonclinical species and plasma protein 
binding is low (< 70%). The PK of filgotinib is generally dose proportional without gender 
differences. The mean terminal half-life after oral administration is 4 and 5 hours in rats and 
dogs, respectively. In the rat, filgotinib showed a rapid and even distribution in most tissues 
throughout the body. High concentrations were observed only in the gastrointestinal (GI) tract 
and urinary bladder. Filgotinib does not penetrate into central nervous system (CNS) tissues. The 
distribution of filgotinib indicates some affinity for melanin-containing tissues. Excretion occurs 
primarily via the urine and feces in rat and dog and is nearly complete within 24 hours (rat) and 
48 hours (dog) post-dosing. The formation of the major metabolite, GS-829845, is mediated by 
carboxylesterases (CES) and is not dependent on cytochrome P450 (CYP); in vitro experiments 
have shown that drug-drug interactions with filgotinib and GS-829845 are unlikely. There is no 
inhibition or induction of CYPs or uridine disphosphate glucuronosyltransferases (UGTs), and 
no relevant inhibition of key drug transporters, by filgotinib or GS-829845.
In rats, filgotinib and GS-829845 had no effects on the respiratory system and CNS and no 
relevant effects on cardiovascular parameters (human ether-a-gogo related gene and dog 
telemetry studies), apart from a slight non-adverse increase in heart rate and arterial pressure 
with GS-829845, at exposures 14-fold that of the Cmax in human subjects dosed with filgotinib 
100 mg once daily. Administration of filgotinib did not affect female fertility but impaired male 
fertility was observed in rats at exposures approximately 30-fold the human exposure at 100 mg 
of filgotinib. The metabolite, GS-829845, did not have any effects on fertility parameters.
In repeat oral dose toxicity studies in both rats and dogs, the primary target tissues identified for 
filgotinib were the lymphoid tissues which are expected based on the pharmacology of JAK 
inhibition. Additional filgotinib-related findings were observed in the male reproductive organs 
of both species, and in the incisor teeth of rats. Effects on the lymphoid system were fully 
reversible. Testicular toxicity demonstrated partial reversibility, however sperm counts remained 

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low. A dose of 100 mg once daily of filgotinib results in an estimated mean clinical area under 
the curve (AUC) of 1.38 μg∙h/mL in subjects with RA, which represents an exposure margin of 
4.8, 3.7, and 6.9-fold when considering the mean AUC in male dogs at the 
no-observed-effect-levels in the 26-week and 39-week chronic toxicity studies, and the 39-week 
targeted exposure toxicity study, respectively. GS-829845-related findings in general repeat dose 
toxicity studies were similar to those of the parent filgotinib, however no testicular toxicity was 
noted following administration of GS-829845.
Filgotinib and GS-829845 are non-genotoxic. In embryofetal development studies, filgotinib and 
GS-829845 caused embryolethality and teratogenicity in rats and rabbits at exposures similar to 
the human exposure at 200 mg once daily of filgotinib in subjects with RA. Exposures 
comparable to the human exposure at 100 mg once daily have not been evaluated in rats or 
rabbits.  
1.2.3.
Additional Clinical Studies of Filgotinib
As of April 2017, filgotinib has been taken by more than 348 healthy volunteers or special 
populations (15 subjects with renal impairment), 959 subjects with RA, 153 subjects with 
Crohn’s disease (CD) and 2 subjects with ulcerative colitis (UC), and has been generally safe and 
well tolerated. A detailed description of all clinical studies can be found in the IB.
In eleven Phase 1 studies conducted in healthy subjects (Studies GPLG0634-CL-101, -102, -103, 
-104, -105, -106, -107, -110, GS-US-417-3900, GS-US-417-3911, and GS-US-417-3916), 
filgotinib administered at doses of up to 450 mg once daily for up to 10 days was safe and well 
tolerated.
In two Phase 2a studies in subjects with RA (Study GLPG0634-CL-201 and -202), dosing with 
filgotinib was well-tolerated and achieved maximal efficacy at a 200 mg daily dose 
(American College of Rheumatology 20% improvement [ACR20] response of 75-92% at 
Week 4).
In two Phase 2b studies, filgotinib at total daily doses of 50 mg, 100 mg, or 200 mg, 
administered in addition to background therapy with methotrexate (MTX) (GLPG0634-CL-203) 
or as monotherapy (GLPG0634-CL-204) was safe and effective in subjects with moderately to 
severely active RA who had an inadequate response to MTX alone.
Currently, Phase 3 studies are ongoing in subjects with RA, UC (Phase 2b/3), and CD, and Phase 
2 Proof of Concept studies are ongoing in Uveitis, Sjogren’s, Lupus, psoriatic arthritis and 
ankylosing spondylitis, small bowel CD and fistulizing CD.
1.3.
Rationale for This Study
Hepatic disease may alter absorption, disposition, and elimination of drugs resulting in PK and 
subsequent pharmacodynamic changes. Hence, the objective of this study is to investigate 
potential changes in the pharmacokinetics of a single-dose of filgotinib in subjects with hepatic 
impairment. Since both filgotinib and its major metabolite GS-829845 exhibit time-independent 

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PK, the administration of filgotinib as a single-dose is expected to predict steady-state PK and 
therefore is deemed satisfactory for this study. This is consistent with recommendations included 
in the FDA Guidance for Industry entitled “Pharmacokinetics in Patients with Impaired Hepatic 
Function:  Study Design, Data Analysis, and Impact on Dosing and Labeling”. 
This study will be conducted in an adaptive manner. Specifically, initial subjects to be enrolled 
will have moderate (CPT Class B) hepatic impairment (Cohort 1). Pharmacokinetic and safety 
data from these subjects will be compared to matched subjects with normal hepatic function. 
Review of Sponsor Safety and PK results obtained from Cohort 1 will indicate whether further 
evaluation in subjects with mild or severe hepatic impairment is needed. Dosing of subjects with 
mild or severe hepatic impairment will occur only after the review of safety and PK from 
subjects with moderate impairment in Cohort 1 (moderate hepatic impairment).
Based on PK properties of filgotinib, the “reduced PK study design” is considered appropriate 
following the FDA Guidance. In humans, filgotinib is highly metabolized to its active metabolite 
GS-829845, primarily by carboxylesterase isoform 2 (CES2) in the intestine and to a lesser 
extent by CES1 in the liver. Following a single dose of [14C]-filgotinib, a majority of the dose 
(86.9%) was recovered in urine, suggesting that renal clearance is the main pathway of 
elimination for filgotinib and its metabolites. GS-829845 (54.0% of the dose) and its 
N-glucuronide derivative (14.6% of the dose) were the major species excreted in urine, followed 
by the parent filgotinib (9.37% of the dose). Among the 15.4% radioactivity recovered in feces, 
GS-829845 and filgotinib accounted for 8.88% and 4.47% of dose, respectively. Based on these 
data, significant changes in plasma exposures of filgotinib or GS-829845 are not expected with 
impairment in hepatic function. Therefore, it is considered safe to evaluate a single dose of 
100 mg filgotinib in subjects with moderate hepatic impairment first, followed by subjects with 
mild or severe hepatic impairment in an adaptive manner, if indicated.
Finally, the data from this study will inform dosing recommendations for subjects with chronic 
inflammatory disease including RA, UC, or CD who have hepatic dysfunction.
1.4.
Rationale for the Dose Selection
A single-dose of 100 mg filgotinib will be tested in this study. This dose is expected to be well 
tolerated based on safety data from single and multiple dose studies in healthy volunteers and 
patients with RA or CD. As of April 2017, 1462 subjects (348 healthy subjects or special 
populations [15 subjects with renal impairment]), 153 subjects with CD, 2 subjects with UC, and 
more than 959 subjects with RA) have received single or multiple doses of filgotinib up to 
450mg for up to 60 weeks in duration in clinical studies. Filgotinib is considered well tolerated 
across these dosing regimens in these subjects. 
Evaluating the 100 mg filgotinib dose in subjects with hepatic impairment is clinically relevant. 
Filgotinib is being tested at 100 mg and 200 mg once daily in Phase 3 programs in subjects with 
RA, UC, or CD. The 100 mg single dose is also chosen to ensure clinically safe filgotinib / 
GS-829845 exposures in study subjects in case of unexpected alteration in filgotinib PK by 
hepatic impairment. Further, since filgotinib exhibits approximately dose-proportional PK, PK 
results from this study (ie, 100 mg single dose) can be extrapolated to other doses (ie, 200 mg) of 
filgotinib.

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1.5.
Risk/Benefit Assessment for the Study
Potential risks of a participant’s study involvement include unknown AEs, general risks 
associated with frequent clinic visits and laboratory blood draws, and the associated pain and 
discomfort of phlebotomy.  Strategies to mitigate these risks include close monitoring of lab 
values as well as AEs.  For this study, frequent assessments of hepatic function will also be 
performed from the collection of both blood and urine samples. Parameters for discontinuation of 
the study drug due to AEs will be well defined and closely followed.
There is no direct benefit to subjects participating in this study; however, data from this study 
will support the development of filgotinib for the treatment of RA and other chronic 
inflammatory conditions. Potential benefits may include the participant’s contribution to the 
sponsor’s understanding of the PK, safety, and tolerability of filgotinib in subjects with hepatic 
insufficiency.
Considering the above, the benefit-risk balance for this study is considered positive.
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2.
OBJECTIVES
The primary objective of this study is as follows:

To evaluate the PK of filgotinib and its metabolite, GS-829845 , in subjects with impaired 
hepatic function relative to matched, healthy controls
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of filgotinib in subjects with normal and impaired 
hepatic function

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3.
STUDY DESIGN
3.1.
Study Design
This protocol describes a Phase 1, open-label, adaptive, single-dose study to evaluate the PK of 
filgotinib and its metabolite, GS-829845, in subjects with impaired hepatic function relative to 
matched, healthy controls. Up to 60 subjects will be enrolled (for up to 48 evaluable). 
Cohort 1 (Moderate Hepatic Impairment): 20 subjects (10 with moderate hepatic impairment 
and 10 matched healthy controls for 8 evaluable subjects per group).
Adaptive Cohort 2 (Severe Hepatic Impairment): 20 subjects (10 subjects with severe hepatic 
impairment and 10 healthy matched controls for 8 evaluable subjects per group).
Adaptive Cohort 3 (Mild Hepatic Impairment): 20 subjects (10 subjects with mild hepatic 
impairment and 10 healthy matched controls for 8 evaluable subjects per group).
Male and nonpregnant, nonlactating female subjects aged 18 through 70 years, inclusive, with 
severely impaired, moderately impaired, mildly impaired, and normal hepatic function will be 
enrolled into the study.  Subjects will be current nonsmokers (no use of tobacco, 
nicotine-containing or THC-containing products within the last 14 days). Each subject in the 
control group will be matched to a subject with impaired hepatic function by age (± 10 years), 
gender, and body mass index (± 15%). A subject with normal hepatic function may serve as a 
matched control across cohorts but may only serve as a matched control to one hepatic impaired 
subject within a cohort.
Subjects in adaptive Cohort 2 (Severe Hepatic Impairment) and Cohort 3 (Mild Hepatic 
Impairment) may be enrolled after the review by Sponsor of safety and PK data from subjects in 
Cohort 1 (Moderate Hepatic Impairment).
An overview of the study design is described below and shown in Figure 3-1.

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Figure 3-1.
High-Level Study Schema
3.1.1.
Cohorts 1 – 3
An overview of the study design is described below and shown in Figure 3-2.
Figure 3-2.
Study Schema 

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3.2.
Study Drug Administration
Study drug will be administered on Day 1 with 240 mL of water following an overnight fast 
(no food or drinks except for water) for at least 10 hours. Subjects will continue to fast until after 
collection of the 4-hour blood sample, relative to study drug dosing. Additionally, subjects will 
be restricted from water consumption 1 hour before until 2 hours after dosing, except for the 
240 mL given with the study treatment. A standardized meal may be provided to subjects after 
collection of the 4-hour blood draw.
Please refer to Section 5.3 for additional information for study drug dosage and administration.
3.3.
Clinic Confinement
Following Screening and admission assessments, eligible subjects will be confined to the study 
center beginning Day -1 until the completion of assessments on Day 6. Subjects will return for 
an in-clinic follow-up (FU) visit on Day 15 (± 1 day).
3.4.
Pharmacokinetic Assessments
Pharmacokinetic assessments will occur on assigned study days as outlined in Table 6-1 and 
Section 6.8.
3.4.1.
Plasma Pharmacokinetic Collection
Plasma concentrations of filgotinib and its metabolite (GS-829845) will be measured and PK 
parameters determined. Plasma concentrations of other metabolites may be determined and PK 
explored.
Protein binding of filgotinib and its major metabolite (GS-829845) will be assessed at their Tmax
time point(s) as well as at another later time point.
3.5.
Samples for Optional Future Research
 
 
 
PPD

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3.6.
Safety Assessments
Safety assessments will be performed through the study as outlined in Table 6-1 and in 
Section 6.9.
3.7.
End of Study
The end of this study will be the last subject’s last observation (or visit).

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Up to 60 unique subjects will be enrolled in the study. Eligible subjects include male and 
nonpregnant, nonlactating female subjects of 18 through 70 years of age, inclusive, with varying 
degrees of hepatic impairment and matched healthy controls. If necessary, replacement subjects 
may be enrolled if subjects do not complete all intensive PK procedures with sponsor approval. 
Replacement subjects will not be enrolled for subjects who discontinue the study due to study 
drug-related AEs.
Those subjects with hepatic impairment will be categorized based upon the CPT classification 
system indicating hepatic impairment as recommended by the United States FDA and European 
Medicines Agency(EMA) and international guidance documents {U.S. Department of Health 
and Human Services Food and Drug Administration Center for Drug Evaluation and Research 
(CDER); Center for Biologics Evaluation and Research (CBER) 2003}. Within the CPT system, 
subjects will be assigned to Class A, B, or C (CPT Class A, B, or C) based on a cumulative score 
evaluating the presence and severity of hyperbilirubinemia, hypoalbuminemia, prolongation of 
INR for coagulation time, ascites, and hepatic encephalopathy. Classification of hepatic 
impairment will be assigned as follows:

Mild: Class A, CPT score of 5-6

Moderate: Class B, CPT score of 7-9

Severe: Class C, CPT score of 10-15
Based on CPT classification, subjects with hepatic impairment and healthy matched controls will 
be enrolled as described in Section 5.1. The control group will consist of matched healthy 
subjects with normal hepatic function. Each subject in the control group will be matched to a 
subject with impaired hepatic function by age (± 10 years), gender, and body mass index 
(± 15%).
4.2.
Inclusion Criteria
4.2.1.
All Subjects
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Have the ability to understand and sign a written informed consent form (ICF), which must 
be obtained prior to initiation of study procedures
2) Be aged 18 through 70 years of age, inclusive at screening
3) Be a nonsmoker. No use of tobacco, nicotine or nicotine-containing or THC-containing 
products within the last 14 days of Day 1

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4) Have a calculated body mass index (BMI) of 18.0 and 36.0 kg/m2 at screening
5) Have a creatinine clearance (CLcr) 60 mL/min (using the Cockcroft-Gault method 
{Cockcroft 1976}) based on serum creatinine and actual body weight as measured at 
screening, ie,
Male:
(140 – Age [years]) (Weight [kg]) CLcr (mL/min)
72 (Serum Creatinine [mg/dL])
Female:
(140 – Age [years]) (Weight [kg]) 0.85 CLcr (mL/min)
72 (Serum Creatinine [mg/dL])
6) Females of childbearing potential (as defined in Appendix 3) must have a negative serum 
pregnancy test at screening and Day -1
7) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described in
Appendix 3
8) Female subjects must refrain from egg donation or harvest from clinic admission 
(eg, Day -1), through the study period, and continuing for at least 35 days after the last dose 
of study drug
9) Male subjects must refrain from sperm donation from clinic admission (eg, Day -1), 
throughout the study period, and continuing for at least 90 days following the last dose of 
study drug
10) Subjects have not donated blood within 56 days of study entry or plasma within 7 days of 
study entry and must refrain from blood donation from clinic admission, throughout the study 
period, and continuing for at least 30 days following the last dose of study drug.
11) Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are 
considered clinically insignificant by the investigator
12) Must be willing and able to comply with all study requirements
4.2.2.
Subjects with Impaired Hepatic Function
Subjects with mild, moderate, or severe hepatic impairment must also meet the following 
additional inclusion criteria to be eligible for participation in the study:
13) Aside from hepatic insufficiency, the subject must, in the opinion of the investigator, be 
sufficiently healthy for study participation based upon medical history, physical examination, 
vital signs, and screening laboratory evaluations
14) Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no clinically 
significant changes within 3 months (or 90 days) prior to study drug administration (Day 1)

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15) Must meet all of the following laboratory parameters at Screening:

ALT value ≤ 10 × ULN

AST value ≤ 10 × ULN

Total bilirubin ≤ 10 x ULN

Albumin ≥ 2.0 g/dL

Absolute neutrophil count ≥ 1,000/mm3

Platelets ≥ 25,000/mm3

Hemoglobin ≥ 8 g/dL

INR ≤ 2.3 (without the use of anticoagulants)

α-fetoprotein < 50 ng/mL
16) Subjects with mild hepatic impairment must have a score on the CPT scale of 5-6 at 
Screening. If a subject’s score changes during the course of the study, the score at Screening 
will be used for classification
17) Subjects with moderate hepatic impairment must have a score on the CPT scale of 7-9 at 
Screening. If a subject’s score changes during the course of the study, the score at Screening 
will be used for classification
18) Subjects with severe hepatic impairment must have a score on the CPT scale of 10-15 at 
Screening. If a subject’s score changes during the course of the study, the score at Screening 
will be used for classification.
19) Subjects with hepatic impairment with comorbid diseases not associated with hepatic 
impairment requiring medication(s) must be taking the medication(s) without a change in 
dose for at least 2 weeks (or 5 half-lives, whichever is longer) prior to dosing. Any change in 
the dosage during this timeframe should be reviewed and approved by the Sponsor.
4.2.3.
Healthy Matched Control Subjects
Healthy matched control subjects must also meet the following additional inclusion criteria to be 
eligible for participation in this study:  
20) Must meet all of the following laboratory parameters at Screening:

INR ≤ 1 × ULN

Albumin ≥ 1 × LLN

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
Total bilirubin ≤ 1 × ULN

AST value ≤ 1 × ULN

ALT value ≤ 1 × ULN

Alkaline phosphatase ≤ 1 × ULN

α-fetoprotein ≤ 1 × ULN
21) Must match in age (± 10 years), gender, and BMI (± 15%) with the respective subject in the 
hepatic impairment group.
22) Must, in the opinion of the investigator, be in good health based upon medical history and 
physical examination, including vital signs.
4.3.
Exclusion Criteria
4.3.1.
All Subjects
Subjects who meet any of the following exclusion criteria will not be enrolled in this study:
1) Pregnant or lactating subjects
2) Participation in any clinical study of an investigational drug/device within 4 weeks or 
5 half-lives (whichever is longer) of the drug prior to Day -1. Exposure to investigational 
biologics should be discussed with the sponsor.
3) Have current alcohol or substance abuse judged by the investigator to potentially interfere 
with subject compliance or subject safety
4) Have a positive test result for human immunodeficiency virus type 1 or type 2 (HIV-1/2) 
antibody or antigen
5) Have poor venous access that limits phlebotomy
6) Receipt of a live attenuated vaccine within 4 weeks prior to Day 1, or planned administration 
of a live attenuated vaccine in the 6 weeks following Day 1
7) Have been treated with systemic (parenteral or oral) corticosteroids, immunosuppressant 
therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to 
receive these agents during the study (eg, corticosteroids, immunoglobulins, and other 
immune- or cytokine-based therapies). Specific exception will be made for orally 
administered systemic corticosteroids, which are allowed until 28 days prior to Day 1. 
Beginning 28 days prior to Day 1, subjects with any systemic corticosteroid treatment 
(parenteral or oral) will be excluded.

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8) Have a history of any of the following:
a) Significant serious skin disease, such as but not limited to rash, food allergy, eczema, 
psoriasis, or urticaria
b) Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatotoxicity)
c) Known hypersensitivity to filgotinib, its metabolites, or to formulation excipients 
(see Section 5)
d) Significant cardiac disease (including history of myocardial infarction based on ECG 
and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or 
dilated cardiomyopathy with left ventricular ejection fraction < 40%), or a family history 
of long QT syndrome or unexplained death in an otherwise healthy individual between 
the ages of 1 and 30 years
e) Primary varicella zoster virus (VZV) infection in the 4 weeks prior to Day 1; or history of 
herpes zoster (HZ) within the 4 weeks prior to Day 1; or any prior history of disseminated 
herpes zoster infection, herpes zoster ophthalmicus, or complication of varicella virus 
infection involving the central nervous system (CNS)
f)
History of syncope, recurrent palpitations, or unexplained dizziness
g) Severe peptic ulcer disease, severe gastroesophageal reflux disease, or other gastric acid 
hypersecretory conditions
h) Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or 
intestinal surgery). A history of cholecystectomy is not exclusionary
i)
Implanted defibrillator or pacemaker
j)
Prior allogeneic bone marrow progenitor cell or solid organ transplantation or currently 
registered on an organ transplantation list
k) Prior placement of a portosystemic shunt (such as TIPS), unless vascular imaging 
indicates the shunt has no current blood flow.
9) Are unable to comply with study requirements or are otherwise believed, by the study 
investigator, to be inappropriate for study participation for any reason.
4.3.2.
Subjects with Impaired Hepatic Function
Subjects with mild, moderate, or severe hepatic impairment meeting any of the following 
additional exclusion criteria are not to be enrolled in this study:
10) Aside from hepatic insufficiency, any serious or active medical or psychiatric illness that, in 
the opinion of the Investigator, would interfere with subject treatment, assessment, or 
compliance with the protocol. This would include any renal, cardiac, hematological, unstable 
hepatic, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, 

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gastrointestinal (including an ulcer), vascular, metabolic (eg, thyroid, or adrenal), or 
infectious disorders, as well as any immunodeficiency, malignancy, or 
spontaneous/unprovoked bleeding, that are clinically significant.
11) Positivity for serum hepatitis B virus surface antigen (HBsAg) at Screening or positivity for 
serum hepatitis B virus core antibody (HBcAb) at Screening
12) Positivity for serum hepatitis C virus (HCV) antibody (Ab) at Screening if accompanied by 
detectable HCV viremia. Subjects with positive serum HCV Ab at screening will undergo 
reflex plasma HCV RNA testing, and subjects with HCV RNA positivity will be excluded. 
Eligibility of those subjects with positive HCV Ab and negative HCV RNA at Screening will 
be allowed based on the investigator’s judgment
13) Positive test for drugs of abuse, including alcohol at Screening or admission, with the 
exception of opioids and tetrahydrocannabinol (THC, marijuana) under prescription and 
Investigator verification for pain management. Subjects who screen positive for 
benzodiazepines may be allowed if prescribed under the care of a physician and after review 
by Investigator and Sponsor.
14) Requires paracentesis > 1 time per month during the past 3 months.
15) Changes in concomitant medications or dosage used to treat symptoms of hepatic impairment 
or associated comorbid conditions within 28 days prior to Day 1. This could lead to clinically 
significant changes in medical conditions during the course of the study that would affect the
ability to interpret potential drug-drug interactions.
16) Any current signs or symptoms of severe hepatic encephalopathy, that in the opinion of the 
Investigator may affect the ability of the subject to provide initial and continuing informed 
consent to participate
17) History of gastric or esophageal variceal bleeding in which varices have not been adequately 
medically or surgically treated, or any history of variceal bleeding in the last 6 months unless 
banded
18) History of hepatorenal or hepatopulmonary syndrome
19) Current signs or symptoms consistent with spontaneous bacterial peritonitis, known active 
spontaneous bacterial peritonitis, or a history of spontaneous bacterial peritonitis within the 
last 6 months
20) Recent hospitalization (within the last 2 months) related to cirrhosis or its complications
21) Confirmed hypotension (defined as < 80 mmHg systolic and/or <50 mmHg diastolic) at 
screening, as measured in the supine position after resting for at least 5 minutes

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22) Suspicion of hepatocellular carcinoma, ie, if α-fetoprotein > 50 ng/mL at Screening, 
enrollment is only allowed if results of appropriate diagnostic studies (eg CT scan or hepatic 
ultrasound) are inconsistent with a diagnosis of hepatocellular carcinoma
All concomitant medications including over-the-counter and herbal products must be 
approved by the Investigator and Medical Monitor prior to study enrollment and study 
drug administration.
4.3.3.
Healthy Matched Control Subjects
Healthy matched controlled subjects meeting any of the following additional exclusion criteria 
are not to be enrolled in this study:
23) A positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) 
antibody
24) Positive test for drugs of abuse, including alcohol at Screening or admission.
25) Have any serious or active medical or psychiatric illness (including depression) that, in the 
opinion of the investigator, would interfere with subject treatment, assessment, or compliance 
with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary 
(including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal 
(including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), 
immunodeficiency disorders, active infection, or malignancy that are clinically significant or 
requiring treatment.
26) History of liver disease
27) Have taken any prescription medications or over-the-counter medications, including herbal 
products, within 28 days prior to start of study drug dosing, with the exception of vitamins 
and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications.

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5.
STUDY DRUGS
5.1.
Enrollment
It is the responsibility of the investigator to ensure that the subject is eligible for the study prior 
to enrollment. Subjects will be assigned a screening number at the time of consent.
At screening, study participants will be assigned to a cohort. Once eligibility has been confirmed 
following completion of the admission study procedures, eligible subjects will be assigned a 
subject number on Day 1 and will receive the study treatments as described in Section 5.3. 
All screening and admission (Day -1) tests and procedures must be completed and reviewed by 
the Investigator prior to the administration of the first dose of study drug on Day 1. Once a 
subject number has been assigned to a subject, it will not be reassigned to another subject. If 
necessary, replacement subjects may be enrolled after discussion and approval from sponsor. A 
new unique subject number will be assigned to the replacement subject. 
A subject number list will be provided to the study center by the sponsor.
5.2.
Description and Handling of Filgotinib
5.2.1.
Formulation
Filgotinib tablets, 100 mg, are beige, capsule-shaped,  film-coated tablets debossed with “GSI” 
on one side and “100” on the other. Each tablet contains the equivalent of 100 mg filgotinib free 
base in the form of filgotinib maleate. In addition to the active ingredient, filgotinib tablets 
contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, 
fumaric acid, pregelatinized starch, silicon dioxide, magnesium stearate, macrogol/PEG 3350, 
polyvinyl alcohol, talc, titanium dioxide, iron oxide yellow, and iron oxide red.
5.2.2.
Packaging and Labeling
Filgotinib tablets, 100 mg, are packaged in white, high density polyethylene bottles (HDPE). 
Each bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap fitted with an 
induction-sealed, aluminum-faced liner. 
Study drugs to be distributed to participating centers  shall be labeled to meet applicable 
requirements of the United States Food and Drug Administration (FDA), EU Guideline to Good 
Manufacturing Practice - Annex 13 (Investigational Medicinal Products) and/or other local 
regulations, as applicable.

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5.2.3.
Storage and Handling
Filgotinib tablets should be stored at controlled room temperature of 25 °C (77 F); excursions 
are permitted between 15 C and 30 C (59 F to 86 F). Storage conditions are specified on the 
label.
Until dispensed to the subjects, all drug products should be stored in a securely locked area, 
accessible only to authorized site personnel. To ensure the stability of the study drug and to 
ensure proper product identification, the drug product should not be stored in a container other 
than the container in which they are supplied.  Consideration should be given to handling, 
preparation, and disposal through measures that minimize drug contact with the body. 
Appropriate precautions should be followed to avoid direct eye contact or exposure when 
handling.
5.3.
Dosage and Administration of Study Drug
Following completion of Screening and Day -1 assessments, eligible subjects will receive a 
single oral dose of 100 mg filgotinib (1 100 mg tablet) on Day 1, in fasting state. Dosing in 
subjects with normal hepatic function will begin after a matched subject with hepatic impairment 
has completed all Day 1 PK assessments.
5.4.
Fasting and Meals
Study drug will be administered on Day 1 with 240 mL of water following an overnight fast 
(no food or drinks except for water) for at least 10 hours. Subjects will continue to fast until after 
collection of the 4-hour blood sample, relative to study drug dosing. Additionally, subjects will 
be restricted from water consumption 1 hour before until 2 hours after dosing, except for the 
240 mL given with the study treatment. A standardized meal may be provided to subjects after 
collection of the 4-hour blood draw.
All meals and/or snacks given to subjects during their stay in the clinical study facility will be 
standardized for all subjects and should be similar in calorie and fat content and taken at 
approximately the same time each day. All meals provided must be approved by the sponsor. 
Components of meals (eg, margarine, jelly, bread) should be given to subjects in individual 
portions (eg, 1 tablespoon) per the approved meal schedule. The provision of meal components 
in bulk (eg, a jar of jelly for subjects to share) should not be practiced. All meals should be given 
at approximately the same time each day (eg, 07:30, 12:00, and 18:00).
5.5.
Dispensing, Accountability, and Disposal or Return of Study Drug
The investigator (or designee, eg, study center pharmacist) will acknowledge receipt of the study 
drug (after reviewing the shipment’s content and condition) from Gilead (or designee). The 
investigator will maintain an accurate inventory of all study drug(s). Each dose of the study 
drug(s) administered at the study center will be administered by qualified study center staff. The 
dose of study drug(s) administered to subjects in the clinic under the supervision of staff will be 

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accurately recorded on the Study Drug Accountability form provided by Gilead (or on equivalent 
documentation maintained by the study center), which indicates the date and quantity of each 
dosage formulation dispensed to individual subjects.
5.5.1.
Study Drug Return or Disposal
Please refer to Section 9.1.7.
5.6.
Concomitant Medications and Other Protocol Restrictions
5.6.1.
Concomitant Medications 
5.6.1.1.
Hepatic Impairment Groups
Concomitant use of certain medications or herbal/natural supplements with study drug may result 
in PK interactions resulting in increases or decreases in exposure of study drug or these 
medications. 
Concomitant medications taken within 30 days of Screening through the FU visit need to be 
recorded in the source documents and Case Report Form (CRF)/electronic Case Report Forms 
(eCRFs).
Subjects with hepatic impairment with comorbid diseases not associated with hepatic impairment 
requiring medication(s) must be taking the medication(s) without a change in dose for at least 
2 weeks (or 5 half-lives, whichever is longer) prior to dosing. Any change in the dosage during 
this timeframe should be reviewed and approved by the Sponsor.
Subjects with hepatic impairment with co-morbid diseases requiring medication(s) must be 
taking the medication(s) without a change in dose within 28 days of Day 1.
All concomitant medications including over-the-counter and herbal products must be approved 
by the Investigator and Medical Monitor prior to study enrollment and study drug administration.
The following medications are prohibited from 28 days prior to Day 1 through discharge:

Any and all illegal or illicit drug use, including use of prescription drugs outside the care of 
the prescribing physician.

Hematologic stimulating agents (eg, erythropoiesis-stimulating agents [ESAs]; granulocyte 
colony stimulating factor [GCSF]; thrombopoietin [TPO] mimetics)

Chronic systemic immunosuppressants including, but not limited to, corticosteroids  
azathioprine, or monoclonal antibodies (eg, infliximab). 

Investigational agents or devices for any indication

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
Filgotinib is a P-gp substrate. Concomitant use of P-gp inducers or inhibitors with filgotinib
may result in changes in exposure of filgotinib or its metabolite GS-829845 and are 
prohibited from 21 days prior to Day 1 through discharge.  Example P-gp inducers and 
inhibitors are listed below:
P-gp inducers: phenobarbital, phenytoin, carbamazepine, rifabutin, rifapentine, rifampin, 
St. John’s wort, and danshen (salvia miltiorrhiza)
P-gp inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, 
conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, 
ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor, and 
verapamil.
Medications for disease conditions excluded from the protocol (eg, HIV-1 or HIV-2, HBV, or 
HCV infection; active cancer; transplantation) are not listed under this Concomitant Medication 
section and are disallowed in the study.
5.6.1.2.
Subjects with Normal Hepatic Function
The following medications are excluded while subjects with normal hepatic function are 
participating in the study:

Any prescription medications or over-the-counter medications including herbal products and 
antacids within 28 days of commencing study drug dosing (Day 1) with the exception of 
vitamins, acetaminophen, ibuprofen and/or hormonal contraceptives. However, the short 
term use of topical hydrocortisone cream or non-corticosteriod ointment to treat minor skin 
irritation due to ECG leads will be allowed. If a subject requires use of a disallowed 
medication, a request for such use must be reviewed by the Sponsor and if approved, subjects 
may continue to participate in the study.  

Any and all illegal or illicit drug use, including use of prescription drugs outside the care of 
the prescribing physician.
5.6.2.
Other Protocol Restrictions

Subjects will be required to refrain from the consumption of food and beverages containing 
alcohol products 72 hours prior to the first dose of study drug and during the course of the 
study through the FU visit.

Subjects will be required to refrain from the use of nicotine or nicotine-containing or 
THC-containing products 14 days prior to first dose of study drug and during the course of 
the study through the FU visit. 

Subjects will be required to refrain from consumption of grapefruit juice, grapefruits, and 
Seville orange juice 72 hours prior to the first dose of study drug and during the course of the 
study through the FU visit.

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
While confined at the study center, tea, coffee, chocolate, and other foods and beverages 
containing caffeine and other methylxanthines will be prohibited on dosing day. At all other 
times, caffeine-containing beverages and foodstuffs may be served or withheld in accordance 
with normal study center practice. Caffeine-containing beverages and foodstuffs will not be 
restricted while subjects are outside of the clinic.

Subjects will be encouraged to avoid strenuous or prolonged exercise, as well as saunas, 
steambaths, and sunbathing or other prolonged ultraviolet exposure, eg, in a tanning salon, 
from the screening evaluation until completion of the FU visit, as these activities are known 
to affect certain clinical laboratory test parameters, (eg, creatine kinase) and will provide 
false indicators of a potentially treatment-related toxicity. 
Upon every admission to the clinic, each subject will be questioned as to their compliance with 
the above protocol restrictions. If a subject is unable to comply with any of the restrictions 
described above, the subject’s continued participation in the study will be reevaluated by the 
investigator in consultation with the sponsor.

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6.
STUDY ASSESSMENTS
The study procedures to be conducted for each subject enrolled in the study are detailed below.
Any deviation from protocol procedures should be noted in the subject’s clinical chart and 
appropriate CRFs/eCRFs. In addition, the sponsor should be promptly notified of any protocol 
deviations. 
The study center will not initiate dosing until the following have all been met:

The institutional review board (IRB)/ethics committee (EC)/other applicable regulatory 
agencies have reviewed and approved the study and the informed consent document.

All requested regulatory documents have been submitted to and approved by Gilead.

A master services agreement and/or study agreement is executed.

The study initiation meeting has been conducted by the Gilead (or designee).
The initiation meeting will include but is not limited to a review of the protocol, the IB, study 
drugs, and investigator responsibilities.
Documentation of the personally signed and dated ICF for each subject, using the study-specific,
IRB/EC-approved ICF, is required before initiating the screening process. 
6.1.
Subject Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
trial enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or trial-wide at any time.
It is the responsibility of the investigator to ensure that subjects are eligible to participate in the 
study prior to enrollment and continue to remain eligible throughout the study.
Once the ICF has been obtained, all screening and admission tests and assessments have been 
assessed, and study eligibility has been confirmed, subjects will be enrolled to receive study drug 
on Day 1.
Subjects will receive the study treatments as described in Section 5.3.

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Table 6-1.
Schedule of Assessments
Study Procedure
Screena
Day -1
Day 1
Days 2-5
Day 6b
Day 15 (± 1 day)c
ETd
Written Informed Consent
X
Medical History 
X
Complete Physical Exam
X
X
X
Symptom-Driven Physical Examinatione
X
X
X
X
Height
X
Weight, BMI
X
X
Vital Signsf
X
X
X
Xg
X
X
X
HIV-1/2, HBV, and HCV Testing
X
Hematologyh
X
Xi
X
X
X
X
Chemistryh
X
Xi
X
X
X
X
Coagulationh
X
Xi
X
X
X
X
α-fetoprotein
X
Urinalysis 
X
Xi
X
X
X
X
Serum Pregnancy Testj
X
Xi
X
X
X
FSHk
X
Urine Drug, Cotinine, and Alcohol Screen 
X
Xi
X
X
12-Lead ECG
X
X
Xl
X
X
X
Enrollmentm
X
Study Drug Administration
X
PK Assessmentsn
X
X
Review Study Restrictions
X
X
X
X
X
Clinic Confinement
X
Review AEs & Concomitant Medicationso
X
a
Prospective subjects should be screened no more than 28 days prior to administration of the first dose of study drug.
b
Subjects will be discharged from the clinic on Day 6, following all morning assessments.
c
Subjects will return for a FU visit on Day 15 (± 1 day).

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d
Assessments will be performed within 72 hours of early termination (ET) from the study.
e
Symptom-driven PEs will be performed during confinement as needed, based on reported signs and symptoms.
f
Vital signs include blood pressure, heart rate, respiration rate, and body temperature.
g
Day 3 only.
h
Hematology, Chemistry, Coagulation: See Section 6.9.5.1for specifics.
i
Two sets of safety labs will be collected upon clinic admission; one will be sent to the central lab and another will be sent to the sites' local lab to obtain results in time for 
enrollment on Day 1.
j
Females of child-bearing potential only.
k
Female subjects < 54 years old with amenorrhea ≥12 months as outlined in Appendix 3
l
2 hours postdose.
m
On Day 1, subjects will be enrolled immediately prior to dosing.
n
Intensive PK sampling will occur relative to dosing of filgotinib on Day 1 at the following time points for each cohort: Day 1: 0 (predose, ≤ 5 min before dose), 0.5, 1, 2, 3, 4, 
5, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose. A blood sample for PK analysis will be collected at the ET visit (if applicable) and may be analyzed.
o
From the time of obtaining informed consent through the first administration of study drug, record all SAEs, as well as any nonserious AEs related to protocol-mandated 
procedures on the AE eCRF.  All other untoward medical occurrences observed during the screening period, including exacerbation or changes in medical history, are to be 
captured on the medical history eCRF. See Section 7, Adverse Events and Toxicity Management for additional details.

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6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Prospective subjects should be screened no more than 28 days prior to administration of the 
first dose of study drug. If a subject does not begin the treatment phase within this 28-day 
window, all screening evaluation procedures must be repeated. Screening laboratory assessments 
may be repeated once within 28 days prior to administration of study drug to rule out laboratory 
error.
A sufficient number of subjects will be screened to identify up to 60 subjects for enrollment. 
Subjects should be instructed to fast (no food or drink, except water), starting from 
midnight (00:00) or earlier, as appropriate, on the evening prior to the screening visit to ensure 
an approximate 8-hour fast prior to the fasted blood sample collection the next morning.
Written informed consent must be obtained from each subject before initiation of any screening 
procedure. After a subject has provided informed consent, the investigator and other study 
personnel will determine if the subject is eligible for participation in the study. This assessment 
will include a review of the inclusion/exclusion criteria and completion of all screening 
procedures as outlined in Table 6-1 and described in the following text. 
Eligible subjects meeting all of the inclusion criteria and none of the exclusion criteria will be 
instructed on all protocol requirements, including the restrictions on concomitant medication 
usage and other substances as well as consumption of food or beverages containing alcohol, 
caffeine, or xanthine. Subjects will be asked to arrive at the study center on Day -1 for admission 
assessments.
From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs, as well as any AE related to protocol-mandated procedures on the AE 
CRF/eCRF. All other untoward medical occurrences observed during the screening period, 
including exacerbation or changes in medical history are to be captured on the medical history 
CRF/eCRF. See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Admission Assessments
6.2.2.1.
Admission
Subjects should be instructed to fast (no food or drink, except water), starting from 
midnight (00:00) or earlier, as appropriate, on the evening prior to the screening visit to ensure 
an approximate 8-hour fast prior to the fasted blood sample collection.
Subjects meeting all eligibility criteria following the screening evaluation will return to the clinic 
for admission assessments on Day -1. The admission evaluations and/or procedures are outlined 
in Table 6-1.

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Prior to dosing on Day 1, the results of the clinical and laboratory evaluations (as described in 
Table 6-1) must be reviewed by the investigator to confirm the continued eligibility of each 
subject to participate in the study. At the time of enrollment, subjects will be assigned a 
sequential subject number as described in Section 5.1. Subjects will remain confined to the study 
clinic for the duration as described in Section 6.2.2.2 and Table 6-1.
6.2.2.2.
Clinic Confinement
Following Screening and admission assessments, eligible subjects will be confined to the study 
center beginning Day -1 until the completion of assessments on Day 6. Subjects will return for 
an in-clinic FU visit on Day 15 (± 1 day).
6.3.
Check-in Assessments
Following completion of screening and Day -1 assessments, eligible subjects will be assigned a 
subject number and receive study treatments as shown in Section 5.3.
6.4.
Treatment Assessments
Study procedures and assessments are outlined in Table 6-1.
6.5.
Posttreatment Assessments
Subjects will return for an in-clinic FU visit on Day 15 (± 1 day).  Study procedures and 
assessments are outlined in Table 6-1.
6.6.
Assessments for Premature Discontinuation from Study
If the subject withdraws from the study, the ET evaluations and/or procedures outlined in 
Table 6-1 should be performed within 72 hours of permanently discontinuing the study drug.
6.7.
Study Stopping Criteria
If ≥ 2 subjects in any cohort experience the same or similar Grade 3 or Grade 4 
treatment-emergent AE or confirmed laboratory abnormality that is not attributable to obvious 
alternative explanation (eg, hematuria occurring in a menstruating female, creatine kinase [CK] 
elevation after strenuous exercise, or triglyceride elevation that is non-fasting, etc), a review of 
all safety data generated in subjects dosed to date will be initiated. The decision as to whether 
and how to proceed with further enrollment will be determined based on the safety review.
6.8.
Pharmacokinetic Assessments
Intensive PK sampling will occur relative to dosing of filgotinib at the following time points:

Day 1: 0 (predose, ≤ 5 minutes prior to dosing), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 
96, and 120 hours postdose

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A blood sample for PK analysis will be collected at the ET visit (if applicable) and may be 
analyzed.
Plasma concentrations of filgotinib and its metabolite (GS-829845) will be measured and PK 
parameters determined. Plasma concentrations of other metabolites may be determined and PK 
explored.
Protein binding of filgotinib and its major metabolite (GS-829845) will be assessed at their Tmax
time point(s) as well as at another later time point.
6.9.
Safety Assessments
Safety will be evaluated throughout the study. Refer to Table 6-1 for a schedule of assessments.
6.9.1.
Electrocardiogram Assessment
Subjects should rest quietly in the supine position for a minimum of 10 minutes prior to each 
scheduled ECG acquisition and should remain in that position until the recording is complete.
There should be no environmental distractions (including TV, radio, video games, and 
conversation) while the subjects are resting prior to and during the recordings. 
Electrocardiograms will be recorded using the site’s standard ECG equipment. All ECGs will be 
obtained using instruments that analyze data using the same algorithms and produce the same 
data for interpretation. Electrode placement will be performed according to the method of 
Wilson, Goldberger, and Einthoven with a check to confirm that the aVR lead is not inverted.
The investigator or other qualified individuals at the study center will review ECGs to assess for 
changes in ECG intervals and morphology as compared with pretreatment ECGs. ECG interval 
measurements output by the machine will be used for bedside safety monitoring.
Collection of additional ECGs for routine safety monitoring at additional time points or days is at 
the discretion of the investigator based on GCP.
6.9.2.
Physical Examination
Physical examinations conducted throughout the study will be a complete physical examination 
or a symptom-directed physical examination, as outlined in Table 6-1. The complete physical 
examination conducted at screening will also include the following assessments:

Review medical history, including history of allergies, prior and current use of nicotine or 
nicotine-containing products, or THC-containing products, alcohol and illegal drug use, and 
prior (within 30 days) and current medication use
6.9.3.
Vital Signs
Vital sign measurements include blood pressure, heart rate, respiration rate, and temperature and 
should be taken once subjects have been seated or in the supine position. Subject position for 
measurement should be kept consistent throughout the study. Refer to Table 6-1 for vital signs 
collection time points.

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6.9.4.
Body Mass Index
Height and weight will be collected at screening for calculation of BMI for inclusion criteria.
6.9.5.
Clinical Laboratory Tests/Assessments
Blood and urine samples for safety evaluations will be collected throughout the study as outlined 
in Table 6-1.
6.9.5.1.
Blood Sampling
Blood samples will be collected for the following laboratory analyses:

Hematology: CBC with differential

Chemistry (fasting): alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), 
triglycerides, total protein, albumin, lactic acid dehydrogenase (LDH), creatine kinase (CK), 
bicarbonate, blood urea nitrogen (BUN), calcium, chloride, creatinine (see below), glucose, 
phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing is 
performed in subjects with total amylase > 1.5 × upper limit of normal [ULN]

Coagulation: PT, PTT, INR

α-fetoprotein

HIV-1 and HIV- 2, HBV(sAg, cAb), and HCV (Ab; if positive, then reflex HCV RNA)
testing

Serum pregnancy test (females of childbearing potential only)

Follicle-stimulating hormone (FSH) testing (female subjects < 54 years old with amenorrhea 
≥12 months)
6.9.5.2.
Urine Samples
Urine samples will be collected for urinalysis and alcohol, drug, and cotinine screen assessments.
6.9.6.
Creatinine Clearance
Weight will be collected at screening to calculate creatinine clearance (CLcr) for inclusion 
criteria.

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6.9.7.
Adverse Events/Concomitant Medications/Protocol Restrictions
Evaluation for AEs, review of concomitant medications, and review of protocol restrictions will 
occur at the times shown in Table 6-1. See Section 7 for more information regarding AEs and 
Sections 4.3 and 5.6.1 for more information about concomitant medications.
6.10.
Sample Storage
 
 
 
PPD

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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject administered a study drug, 
which does not necessarily have a causal relationship with the treatment. An AE can, therefore,
be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the 
use of a study drug, whether or not considered related to the study drug. Adverse events may also 
include pre- or posttreatment complications that occur as a result of protocol-specified 
procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. 
Preexisting events that increase in severity or change in nature during or as a consequence of 
participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an AE and must be reported.

Preexisting diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.6)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and that is not related to a protocol-associated procedure is 
not an AE. It is considered to be preexisting and should be documented on the medical 
history eCRF.
7.1.2.
Serious Adverse Events
A SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

Inpatient hospitalization or prolongation of existing hospitalization

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction; such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
drug using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study drug. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity 
The severity of AEs will be graded using the modified Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.03. For each episode, the highest grade attained should be 
reported.

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If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: Grade 1 
(mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening) or Grade 5 (fatal) to 
describe the maximum intensity of the adverse event. For purposes of consistency with the 
modified CTCAE, these intensity grades are defined in Table 7-1 and Appendix 4.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated
Grade 2
Moderate
Local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL*
Grade 3
Severe
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**
Grade 4
Life-threatening
Urgent intervention indicated
Grade 5
Death
Death related AE
*
Activities of Daily Living (ADL) Instrumental ADL refer to opening preparing meals, shopping for groceries or clothes,
using the telephone, managing money, etc.
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not
bedridden.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
7.3.1.
Requirements for Collection Prior to Study Drug Initiation
After obtaining informed consent, but prior to initiation of study drug, all SAEs and AEs related 
to protocol-mandated procedures should be reported on the eCRF.
7.3.1.1.
Adverse Events
Following initiation of study treatment, collect all AEs, regardless of cause or relationship, until 
30 days after last administration of study drug must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined FU period.
7.3.1.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment FU period, must be reported to the eCRF 
database and Pharmacovigilance & Epidemiology (PVE) as instructed. This also includes any 
SAEs resulting from protocol-associated procedures performed after informed consent is signed.

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Any SAEs and deaths that occur after the posttreatment FU visit but within 30 days of the 
last dose of study drug, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after days of the last dose of study drug; 
however, if an investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of study drug, the investigator should promptly 
document and report the event to Gilead PVE

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
7.3.1.3.
Electronic Serious Adverse Event Reporting Process 

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead PVE within 24 hours of an investigator’s knowledge of the event. 
Detailed instructions may be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically (eg, the eCRF 
database is not functioning), record the SAE on the paper SAE reporting form and submit 
within 24 hours as described above.
Gilead PVE
Fax: 
Email: 

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
PPD
PPD

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7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable United States 
(US) FDA Code of Federal Regulations, the European Union Clinical Trials Directive 
(2001/20/EC) and relevant updates, and other country-specific legislation or regulations, Gilead 
may be required to expedite to worldwide regulatory agencies reports of SAEs, serious adverse 
drug reactions (SADRs), or SUSARs. In accordance with the EU Clinical Trials Directive 
(2001/20/EC), Gilead or a specified designee will notify worldwide regulatory agencies and the 
relevant independent ethics committee (IEC) in concerned member states of applicable SUSARs
as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Clinical Laboratory Abnormalities
Laboratory abnormalities are usually not recorded as AEs or SAEs.  However, laboratory 
abnormalities (eg, clinical chemistry, hematology, and urinalysis) independent of the underlying 
medical condition that require medical or surgical intervention or lead to interventional 
medicinal product interruption or discontinuation must be recorded as an AE, as well as an SAE, 
if applicable.  In addition, laboratory or other abnormal assessments (eg, ECG, X-rays, vital 
signs) that are associated with signs and/or symptoms must be recorded as an AE or SAE if they 
meet the definition of an AE (or SAE) as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia) not the 
laboratory result (eg, decreased hemoglobin).
Adverse events will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA). Severity should be recorded and graded according to the
modified CTCAE, version 4.03 (Appendix 4).
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3.
For study specific stopping criteria, please refer to Section 6.7.

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7.6.
Toxicity Management 
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead medical monitor, who will have a discussion with the investigator and decide the 
appropriate course of action.  Whether or not considered treatment-related, all subjects 
experiencing AEs must be monitored periodically, when feasible, until symptoms subside, any 
abnormal laboratory values have resolved or returned to baseline levels or they are considered 
irreversible, or until there is a satisfactory explanation for the changes observed.
Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing as soon as practical to do so, and preferably within 3 calendar days after receipt of the 
original test results and followed until resolution or until stable, if possible. Refer to Appendix 2
for additional details on toxicity management.
Any questions regarding toxicity management should be directed to the Gilead medical monitor.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include: all reports of medication error, abuse, misuse, overdose;
occupational exposure with an AE; AEs in an infant following exposure from breastfeeding;
reports of AEs associated with product complaints; and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively that is above the maximum recommended dose 
as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
Occupational exposure is the exposure to a medicinal product as a result of one's professional or 
non-professional occupation.

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7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug FU period, to 
Gilead PVE using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy. 
Refer to Section 7.3and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead PVE using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead PVE by emailing
 or
faxing
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of pregnancy should 
continue until its conclusion. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead PVE by 
faxing
 or emailing
Refer to Appendix 3, Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study drug and/or Gilead concomitant 
medications but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
PPD
PPD
PPD
PPD

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Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.

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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is as follows:

To evaluate the PK of filgotinib and its metabolite GS-829845 in subjects with impaired 
hepatic function relative to matched, healthy controls
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of filgotinib in subjects with normal and impaired 
hepatic function
8.1.2.
Primary Endpoint
The primary endpoints are PK parameters (e.g., AUClast, AUCinf, and Cmax) for filgotinib and
GS-829845.
8.1.3.
Secondary Endpoint
The secondary endpoints include incidences of AEs, laboratory abnormalities, abnormal findings 
in vital signs and safety ECG monitoring.
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Enrolled
The All Enrolled Analysis Set will include all subjects enrolled into the study after screening. 
This is primary analysis set for listings.
8.2.1.2.
Safety
The Safety Analysis Set will include all enrolled subjects who received 1 dose of filgotinib. 
8.2.1.3.
Pharmacokinetics
The PK Analysis Set will include all enrolled subjects who received 1 dose of filgotinib and had 
at least 1 nonmissing PK concentration datum of filgotinib or its metabolite GS-829845 reported 
by PK lab.  

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8.3.
Data Handling Conventions
For summary statistics, PK concentration values below the limit of quantitation will be treated as 
zero at predose and 1-half of the lower limit of quantitation (LLOQ) for postdose time points.
Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation will be imputed to the value of the lower or upper limit minus or plus 
1 significant digit, respectively (eg, if the result of a continuous laboratory test is < 20, a value of 
19 will be assigned; if the result of a continuous laboratory test is < 20.0, a value of 19.9 will be 
assigned).
Missing data can have an impact upon the interpretation of the study data. As this study is of 
short duration, it is anticipated that missing data will be minimal. In general, values for missing 
data will not be imputed. However, a missing pretreatment laboratory result would be treated as 
normal (ie, no toxicity grade) for the laboratory abnormality summary.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements, such as height, weight and BMI, will be summarized 
and descriptive statistics will be provided. 
Demographic summaries will include sex, race/ethnicity, enrollment, and age.
8.5.
Interim Analysis
Review of available safety and PK data will be conducted by the sponsor to facilitate the 
decision on whether or not to conduct the adaptive cohorts.
8.6.
Safety Analysis
All safety data collected on or after the date that study drug was first administered up to the date 
of last dose of study drug plus 30 days will be summarized by hepatic function group using 
Safety Analysis Set. 
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug
administration page in eCRF. Exposure data will be listed.
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term, high-level term, preferred term (PT), and lower-level term 
will be attached to the clinical database.
Adverse event data will be listed by subject. Treatment-emergent AEs (TEAEs), serious TEAEs, 
and TEAEs leading to discontinuation of study will be summarized by hepatic function group, 
SOC, and PT using the current version of MedDRA. 

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8.6.3.
Laboratory Evaluations
Listings of individual subject laboratory results will be provided. Laboratory results and change 
from predose values for selected lab tests will be summarized by hepatic function group at 
scheduled visits. The incidence of treatment-emergent graded laboratory abnormalities will be 
summarized by hepatic function group.
8.6.4.
Other Safety Evaluations
Vital signs and ECG data will be summarized by hepatic function group.
8.7.
Pharmacokinetic Analysis
Plasma concentrations over sampling time and PK parameters (Cmax, Tmax, Clast, Tlast, λz, AUClast, 
AUCinf, %AUCexp, t½, CL/F, and Vz/F, as appropriate)for filgotinib and GS-829845 will be listed 
and summarized by hepatic function group using descriptive statistics (eg, sample size, mean, 
SD, %CV, median, first quartile, third quartile, minimum, and maximum).
An analysis of variance appropriate for a parallel design will be fitted to the natural logarithmic 
transformation of PK parameters (AUClast, AUCinf, and Cmax) for filgotinib and GS-829845. 
Two-sided 90% CIs will be calculated for the GLSM ratios of PK parameters between hepatic 
impairment group versus the matched control (normal hepatic function) group. If the 2-sided 
90% CIs of the GLSM ratio for AUClast, AUCinf, and Cmax of filgotinib or GS-829845 falls within 
the [50%, 200%] bound, the null hypothesis that subjects with hepatic impairment exhibit PK 
parameter change of at least 2-fold for filgotinib or GS-829845 compared with subjects with 
normal liver function will be rejected.
Protein binding of filgotinib and GS-829845 at their Tmax and another later time point will be 
summarized by hepatic function group using descriptive statistics. Unbound PK parameters such 
as CLu/F, and Vzu/F will be calculated as appropriate and summarized by hepatic function 
group. Relationships between measures of hepatic function (ie, CPT score, serum albumin, total 
bilirubin, prothrombin time, and International Normalized Ratio [INR]) and primary 
filgotinib/GS-829845 PK parameters will be evaluated.
8.8.
Sample Size
With 16 (8 per group) evaluable subjects, the estimated two-sided 90% CI of the geometric 
least-square mean (GLSM) ratio of test vs reference groups, with regards to PK parameters 
(AUC and Cmax) would be within (50%, 200%) with over 95% probability, if the estimated 
GLSM ratio were 1.0. This is assuming the SDs for PK parameters between subjects within each 
group is no more than 0.347 (or 0.203) for the natural logarithm-transformed PK parameters for 
filgotinib (or GS-829845). Such assumptions are supported by PK data from a prior Gilead study 
of filgotinib (GS-US-417-3900) with 100 mg dose in healthy volunteers. An overage of 
2 subjects per group will be enrolled in order to accommodate subject drop-outs, so a total 
sample size of 20 subjects (10 per group) for each cohort will be required.

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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonization (ICH) guidelines, or with the laws 
and regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the EU Clinical Trials 
Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of GCP, as outlined in 21 Code of 
Federal Regulations (CFR) 312, Subpart D, “Responsibilities of Sponsors and Investigators,” 
21 CFR, Part 50, "Protection of Human Subjects," and 21 CFR, Part 56, "Institutional Review 
Boards."
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 
"Financial Disclosure by Clinical Investigators," providing documentation of their financial 
interest or arrangements with Gilead, or proprietary interests in the study drug under study. This 
documentation must be provided prior to the investigator’s (and any subinvestigator’s) 
participation in the study. The investigator and subinvestigator agree to notify Gilead of any 
change in reportable interests during the study and for 1 year following completion of the study. 
Study completion is defined as the date when the last subject completes the protocol-defined 
activities.
9.1.2.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) to an IRB/EC. The investigator will not begin any study subject activities until approval 
from the IRB/EC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/EC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/EC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.

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9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB/EC-approved ICF for documenting written informed 
consent. Each ICF will be appropriately signed and dated by the subject or the subject’s legally 
authorized representative and the person conducting the consent discussion, and also by an 
impartial witness if required by IRB/EC local requirements.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law), and an identification code will be recorded on any 
form or biological sample submitted to the sponsor, IRB/EC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions or in accordance 
with local regulations. NOTE: The investigator must keep a screening log showing codes, names, 
and addresses for all subjects screened and for all subjects enrolled in the study. Subject data will 
be processed in accordance with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
IB, this protocol, eCRF, the study drug, and any other study information, remain the sole and 
exclusive property of Gilead during the conduct of the study and thereafter. This information is 
not to be disclosed to any third party (except employees or agents directly involved in the 
conduct of the study or as required by law) without prior written consent from Gilead. The 
investigator further agrees to take all reasonable precautions to prevent the disclosure by any 
employee or agent of the study site to any third party or otherwise into the public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator’s study file and (2) subject 
clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF, IRB/EC and 
governmental approval with correspondence, ICF, drug records, staff curriculum vitae and 
authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender)

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria)

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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end dates (including dose regimen) of study drug, including dates of dispensing and 
return

Record of all AEs and other safety parameters (start and end dates, and including causality 
and severity)

Concomitant medication (including start and end dates, dose if relevant, and dose changes)

Date of study completion and reason for early discontinuation, if it occurs
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject enrolled, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. The eCRF should 
be completed on the day of the subject visit to enable the sponsor to perform central monitoring 
of safety data, whenever possible. The Eligibility Criteria eCRF should be completed only after 

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all data related to eligibility have been received and the subject has been enrolled. Subsequent to 
data entry, a study monitor will perform source data verification within the electronic data 
capture system. Original entries as well as any changes to data fields will be stored in the audit 
trail of the system. Prior to database lock (or any interim time points as described in the clinical 
data management plan), the investigator will use his/her login credentials to confirm that the 
forms have been reviewed, and that the entries accurately reflect the information in the source 
documents. The eCRF captures the data required per the protocol schedule of events and 
procedures. System-generated or manual queries will be issued to the investigative site staff as 
data discrepancies are identified by the monitor or internal Gilead staff who routinely review the 
data for completeness, correctness, and consistency. The site coordinator is responsible for 
responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update (eg, data entry 
error). At the conclusion of the study, Gilead will provide the site with a read-only archive copy 
of the data entered by that site. This archive must be stored in accordance with the records 
retention requirements outlined in Section 9.1.5.
9.1.7.
Study Drug Accountability and Return
Where possible, IMP should be destroyed at the site. At the start of the study, the study monitor 
will evaluate each study center’s IMP disposal procedures and provide appropriate instruction for 
disposal or return of IMP supplies. If the site has an appropriate standard operating procedure
(SOP) for drug destruction as determined by Gilead Sciences, the site may destroy used 
(empty or partially empty) and unused IMP supplies as long as performed in accordance with the 
site’s SOP. This can occur only after the study monitor has performed drug accountability during 
an on-site monitoring visit.
A copy of the site’s IMP Disposal SOP or written procedure (signed and dated by the 
investigator or designee) will be obtained for Gilead site files. If the site does not have 
acceptable procedures in place, arrangements will be made between the site and Gilead
(or Gilead’s representative) for return of unused study drug supplies. If IMP is destroyed on site, 
the investigator must maintain accurate records for all IMPs destroyed. Upon study completion, 
copies of the IMP accountability records must be filed at the site. Another copy will be returned 
to Gilead.
The study monitor will review study drug supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRB/EC, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.

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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to IRB/EC in 
accordance with local requirements and receive documented IRB/EC approval before 
modifications may be implemented.
9.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency(ies). Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases. 
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly 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.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator's meetings). If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.

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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both Gilead and the investigator reserve the right to terminate the study at any time. Should this 
be necessary, both parties will arrange discontinuation procedures and notify the subjects, 
appropriate regulatory authority(ies), IRBs, and ECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.

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10.
REFERENCES
Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors 
for inflammatory diseases. J Med Chem 2014;57 (12):5023-38.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER); Center for Biologics Evaluation and Research 
(CBER). Guidance for Industry. Pharmacokinetics in Patients with Impaired 
Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and 
Labeling.  May, 2003.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Management of Clinical and Laboratory Adverse Events
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03

PPD
PPD

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Appendix 2.
Management of Clinical and Laboratory Adverse Events

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Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
The administration of filgotinib in embryo-fetal animal development studies resulted in 
decreased numbers of viable rat fetuses, increased resorptions, and visceral and skeletal 
malformations. Similar effects were noted in the rabbit. A safety margin relative to human 
exposure has not been identified. Filgotininb is contraindicated during pregnancy.
For participation in this study, all subjects of childbearing potential must agree to the use of
highly effective contraception as outlined below.
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming postmenopausal unless the 
subject is permanently sterile or has medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of < 54 years of age with amenorrhea of ≥ 12 months may also be considered 
postmenopausal if their FSH level is in the postmenopausal range and they are not using 
hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age. Bilateral tubal ligation is not considered 
permanent sterilization.
b) Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless the subject is permanently sterile by bilateral orchidectomy or medical 
documentation. Vasectomy is not considered permanent sterilization.
2) Contraception Requirements for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Filgotinib is contraindicated in pregnancy as there is a possibility of human 
teratogenicity/fetotoxicity in early pregnancy based on non-clinical data. Data from a drug-drug 
interaction study of filgotinib and hormonal contraceptives (GS-US-417-3916) demonstrated that 
filgotinib does not alter the pharmacokinetics of a representative hormonal contraceptive
levonorgestrel/ethinyl estradiol.

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For female subjects, hormonal contraceptives will be permitted as a form of contraception when 
used a conjunction with a barrier method (preferably a male condom). For male subjects, male 
condom should be used; for their female partners of childbearing potential, an accepted 
contraceptive method should also be considered. Details are outlined below.
Please refer to the latest version of the filgotinib IB for additional information.
b) Contraception Requirements for Female Subjects
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. Women must have a negative serum pregnancy test at Screening and on 
Day -1 prior to study drug treatment. Pregnancy tests will be performed throughout the study 
period (refer to Table 6-1).
Female subjects must agree to use one of the following methods (where permitted and used per 
local prescribing label) from Screening until 35 days following the last dose of study drug.

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below.
Intrauterine device (IUD) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success at least 3 months after procedure, with 
documentation of sperm-free ejaculate)
These above described methods are considered preferred methods of highly effective 
contraception in this protocol.
Female subjects who wish to use a hormonally based method must agree to use it in conjunction 
with a barrier method (used either by the female subject or by her male partner). Female subjects 
who utilize a hormonal contraceptive as one of their birth control methods must have 
consistently used the same method for at least three months prior to study dosing.

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Hormonally-based contraceptives and barrier methods permitted for use in this protocol are as 
follows:

Hormonal methods (subject must agree to use with a barrier method, preferably, with a male 
condom)
Oral contraceptives (either combined estrogen/progestin or progesterone only)
Injectable progesterone
subdermal contraceptive implant
Transdermal contraceptive patch
Contraceptive vaginal ring

Barrier methods (subject must agree to use with a hormonal method)
Male or female condom, with or without spermicide
Diaphragm with spermicide
Cervical cap with spermicide
Sponge with spermicide

All female subjects must also agree to refrain from egg donation and in vitro fertilization 
during study participation and for at least 35 days after the last study drug dose.
3) Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure to the male subject’s seminal fluid. Therefore, male subjects with female 
partners of childbearing potential must agree to use condoms during study participation and for 
90 days after the last study drug dose. Female partners of male study subjects should consider 
using one of the above methods of contraception as well. Male subjects must also agree to refrain 
from sperm donation during treatment and until at least 90 days after the end of dosing.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.

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5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 35 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant within 90 days of the last dose of study drug
must report the information to the investigator. 
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in
Section 7.7.2.1.

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Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Please refer to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, 
which can be found at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
The only modification to the CTCAE criteria is the addition of a Grade 1 upper respiratory 
infection as follows:
CTCAE 
v4.0 Term
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
CTCAE v4.03 
AE Term 
Definition
Upper 
respiratory 
infection
Mild 
symptoms; 
symptomatic 
relief 
(eg, cough 
suppressant, 
decongestant)
Moderate 
symptoms; 
oral 
intervention 
indicated 
(eg, antibiotic, 
antifungal, 
antiviral)
IV antibiotic, 
antifungal, or 
antiviral 
intervention 
indicated; 
radiologic, 
endoscopic, or 
operative 
intervention 
indicated
Life-
threatening 
consequences; 
urgent 
intervention 
indicated
Death
A disorder 
characterized by 
an infectious 
process involving 
the upper 
respiratory tract 
(nose, paranasal 
sinuses, pharynx, 
larynx, or 
trachea).