A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Avacopan in Subjects With Normal Renal Function and Subjects With End-Stage Renal Disease (ESRD) Requiring Hemodialysis
Phase: PHASE1
Conditions: End-Stage Renal Disease (ESRD)
Sponsor: Amgen

Protocol 
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AMG 569 20230265 
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Protocol 
A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, 
Safety, and Tolerability of Avacopan in Subjects with Normal Renal Function 
and Subjects with End-Stage Renal Disease (ESRD) Requiring Hemodialysis 
Protocol Amendment 1 Status: Final 
Original Protocol Date: 26 April 2024 
Protocol Amendment 1 Date: 24 June 2024 
Investigational Product: Avacopan 
Amgen Protocol Reference Number: 20230265 
Fortrea Study Number: 8530204 
  
 
 
Sponsor: 
Amgen, Inc. 
One Amgen Center Drive 
Thousand Oaks, California 91320 
 
 
This protocol was developed, reviewed, and approved in accordance with Fortrea’s 
standard operating procedures. This format and content of this protocol is aligned with 
Good Clinical Practice: Consolidated Guidance (ICH E6). 
 

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Confidentiality Notice 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staffs and 
members of the Institutional Review Board/Independent Ethics Committee/Institutional 
Scientific Review Board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number: US sites, 1-800-77-AMGEN; Amgen’s general 
number in the US, 1-805-447-1000. 

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INVESTIGATOR AGREEMENT 
I have read the attached protocol entitled “A Phase 1, Open-label, Single-dose Study to Evaluate 
the Pharmacokinetics, Safety, and Tolerability of Avacopan in Subjects with Normal Renal 
Function and Subjects with End-Stage Renal Disease (ESRD) Requiring Hemodialysis” dated 24 
June 2024 and agree to abide by all provisions set forth therein. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite Guideline 
on Good Clinical Practice (GCP), Declaration of Helsinki, and applicable national or regional 
regulations/guidelines.  
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of Amgen Inc. 
I agree not to share the confidential information contained in this document without the prior 
written consent of Amgen Inc. 
 
_______________________________ 
Signature 
 
 
_______________________________ 
____________________________ 
Name of Investigator  
Date (DD Month YYYY) 
 
_______________________________ 
Title and Role of Investigator 
 
_______________________________ 
Institution Name 
 
_______________________________ 

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Address and Telephone Number of Institution 
 
_______________________________________ 
 
 
 
 
 
                                  

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SYNOPSIS 
Title of study: A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, 
Safety, and Tolerability of Avacopan in Subjects with Normal Renal Function and Subjects 
with End-Stage Renal Disease (ESRD) Requiring Hemodialysis 
Objectives:  
The primary objective of the study is: 
 
to evaluate the pharmacokinetics (PK) of avacopan and metabolite (M1) after a single 
dose of avacopan in subjects with normal renal function and subjects with ESRD 
requiring hemodialysis (HD). 
The secondary objective of the study is: 
 
to evaluate the safety and tolerability of a single dose of avacopan in subjects with 
normal renal function and subjects with ESRD requiring HD. 
Study design: 
This will be a Phase 1, open-label, single-dose, parallel group study to evaluate the PK, safety, 
and tolerability of avacopan in subjects with normal renal function (Group 1) and subjects with 
ESRD requiring HD (Group 2). After informed consent is obtained, potential subjects will be 
screened to assess their eligibility to enter the study within 28 days prior to the first dose 
administration. 
Subjects in Group 1 (normal renal function) will be admitted into the Clinical Research Unit 
(CRU) on Day -1 and will be confined to the CRU until discharge on Day 8.  
Subjects in Group 1 will receive a single 
 dose of avacopan on Day 1 under fed 
conditions. Following discharge on Day 8, subjects will return to the CRU on Days 12, 15, and 
18 (end of study [EOS] visit) for outpatient visits.  
Subjects in Group 2 (ESRD requiring HD) will receive a single dose of 
 avacopan under 
fed conditions on Day 1 in each of the 2 treatment periods (Period 1/on HD and Period 2/off 
HD). Subjects in Group 2 will be admitted into the CRU on Period 1 Day -1. Subjects in Group 
2 Period 1 (on HD) will receive a single 
 dose of avacopan on Period 1 Day 1, 4 hours 
prior to the start of HD. Subjects will continue to receive HD on Days 3, 5, and 8 (prior to 
discharge). Following discharge on Day 8, subjects will return to the CRU on Period 1 Days 
12, 15, and 18 for outpatient visits. Subjects in Group 2 will be re-admitted into the CRU for 
Period 2 Day -1 on the day of their HD. Period 1 Day 18 may occur on the same day as Period 
2 Day -1. Subjects will receive a single 
 dose of avacopan on Period 2 Day 1 on an off-
HD day (one day after the HD session on Period 2 Day -1). Subjects will continue to receive 
HD on Days 3, 5, and 7. Subjects will be confined to the CRU until discharge on Period 2 Day 
8. Following discharge on Period 2 Day 8, subjects in Group 2 will return to the CRU on 
Period 2 Days 12, 15, and 18 (EOS) for outpatient visits. There will be no washout between 
Day 18 of Period 1 and Check-in for Period 2 for subjects in Group 2.  
Number of subjects: 
Approximately 12 subjects will be enrolled in 2 groups (Groups 1 and 2). Approximately 
6 subjects will be enrolled in each group. 
Diagnosis and main criteria for inclusion: 
Male subjects or female subjects, 18 to 75 years of age (inclusive), and body mass index of 18 
to 40 kg/m2 with normal renal function or ESRD requiring HD. 
Investigational products, dose, and mode of administration: 
Investigational Medicinal Product: 
 avacopan oral dose under fed conditions 
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Duration of subject participation in the study: 
Planned Screening duration: 4 weeks. 
Planned study duration (Screening to EOS): Group 1: approximately 7 weeks,  
Group 2: approximately 9 weeks.  
Primary Endpoints: 
The primary endpoints for this study are avacopan and M1 PK parameters: maximum observed 
plasma concentration (Cmax); area under the plasma concentration-time curve (AUC) from time 
zero to time of last quantifiable concentration (AUClast); area under the plasma 
concentration-time curve from time zero to infinity (AUCinf); area under the plasma 
concentration time curve from time zero to 48 hours (AUC0-48), or other partial area 
comparisons, as appropriate; and HD clearance of drug (and metabolite) from plasma (CLD). 
Secondary Endpoints: 
Secondary endpoints for this study are: treatment-emergent adverse events and serious adverse 
events. 
Statistical methods: 
The primary PK parameters are Cmax and AUC. All other PK parameters will be regarded as 
secondary and will not be subject to inferential statistical analysis. To determine the effect of 
renal impairment on the PK of avacopan and M1, the ratios (test/reference) for the model-
estimated Cmax, AUC0-48, and AUCinf for the ESRD group (test) relative to the group with 
normal renal function (reference) will be generated, along with 90 confidence intervals. 
Applicable PK parameters in the ESRD group on-HD days and off-HD days may also be 
compared. 
 
The final safety analysis for the study will be performed at EOS. Adverse events will be 
summarized using descriptive methodology. Each adverse event will be coded using the 
Medical Dictionary for Regulatory Activities. Endpoints for clinical laboratory tests, 
electrocardiogram, and vital signs will be summarized. 
 
Additional details will be included in the Statistical Analysis Plan. 

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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................5 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS ...........................................................................................................8 
LIST OF TABLES AND FIGURES........................................................................................11 
LIST OF ABBREVIATIONS ..................................................................................................12 
1. 
INTRODUCTION ...........................................................................................................14 
1.1. 
Background ............................................................................................................14 
1.2. 
Pharmacokinetics ...................................................................................................14 
1.3. 
Study Rationale ......................................................................................................15 
1.4. 
Benefit-risk Assessment.........................................................................................15 
1.4.1. 
Therapeutic Context .....................................................................................15 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................16 
2.1. 
Objectives ..............................................................................................................16 
2.2. 
Endpoints ...............................................................................................................17 
2.2.1. 
Primary Endpoints .......................................................................................17 
2.2.2. 
Secondary Endpoints ...................................................................................17 
3. 
INVESTIGATIONAL PLAN ..........................................................................................17 
3.1. 
Overall Study Design and Plan ..............................................................................17 
3.2. 
Discussion of Study Design ...................................................................................22 
3.3. 
Selection of Doses in the Study .............................................................................22 
4. 
SELECTION OF STUDY POPULATION .....................................................................22 
4.1. 
Inclusion Criteria ...................................................................................................22 
4.2. 
Exclusion Criteria ..................................................................................................23 
4.3. 
Screen Failures and Rescreening ...........................................................................27 
4.4. 
 ........................................................................28 
4.5. 
Subject Withdrawal and Replacement ...................................................................28 
4.6. 
Study Termination .................................................................................................28 
4.7. 
Discontinuation of Study Treatment (Group 2 only) .............................................29 
5. 
STUDY TREATMENTS .................................................................................................30 
5.1. 
Investigational Product ..........................................................................................30 
5.2. 
Investigational Product Administration .................................................................31 
5.3. 
Treatment of Overdose ..........................................................................................31 
5.3.1. 
Medical Devices...........................................................................................31 
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5.3.2. 
Product Complaints ......................................................................................31 
5.4. 
Randomization .......................................................................................................31 
5.5. 
Blinding..................................................................................................................32 
5.6. 
Treatment Compliance ...........................................................................................32 
5.7. 
Drug Accountability...............................................................................................32 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................32 
6.1. 
Concomitant Therapies ..........................................................................................32 
6.2. 
Diet .........................................................................................................................33 
6.3. 
Smoking .................................................................................................................33 
6.4. 
Exercise ..................................................................................................................34 
6.5. 
Blood Donation ......................................................................................................34 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................34 
7.1. 
Pharmacokinetic Assessments ...............................................................................34 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................34 
7.1.2. 
Analytical Methodology ..............................................................................35 
7.2. 
Safety and Tolerability Assessments .....................................................................35 
7.2.1. 
Adverse Events and Serious Adverse Events: Time period and Frequency 
for Collecting and Reporting Safety Event Information ..............................35 
7.2.2. 
Clinical Laboratory Evaluations ..................................................................39 
7.2.3. 
Vital Signs ....................................................................................................39 
7.2.4. 
12-lead Electrocardiogram ...........................................................................40 
7.2.5. 
Physical Examination...................................................................................40 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................40 
8.1. 
Determination of Sample Size ...............................................................................40 
8.2. 
Analysis Populations ..............................................................................................41 
8.2.1. 
Pharmacokinetic Population ........................................................................41 
8.2.2. 
Safety Population .........................................................................................41 
8.3. 
Pharmacokinetic Analyses .....................................................................................41 
8.4. 
Safety Analysis ......................................................................................................42 
8.5. 
Interim Analysis .....................................................................................................42 
9. 
REFERENCES ................................................................................................................42 
10. APPENDICES .................................................................................................................43 
Appendix 1: Safety Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting of Adverse Events and Serious Adverse Events ..........44 
Definition of Adverse Event ........................................................................................44 
Definition of Serious Adverse Event ...........................................................................45 

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Recording Adverse Events and Serious Adverse Events .............................................47 
Evaluating Adverse Events and Serious Adverse Events ............................................49 
Reporting of Serious Adverse Event............................................................................50 
Appendix 2: Clinical Laboratory Evaluations ...................................................................54 
Appendix 3: Contraception Requirements .........................................................................55 
Appendix 4: Collection of Pregnancy and Lactation Information .....................................58 
Appendix 5: Sample Storage and Destruction ...................................................................62 
Appendix 6: Regulatory, Ethical, and Study Oversight Considerations ............................63 
Appendix 7: Hepatotoxicity: Suggested Actions and Follow-up Assessments (Group 1 
only) .......................................................................................................................68 
Appendix 8: Hepatotoxicity Stopping Rules: Suggested Actions and Follow-up 
Assessments (Group 2 only) ..................................................................................71 
Appendix 9: Schedule of Assessments ..............................................................................76 
 

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LIST OF TABLES AND FIGURES 
Table 1: 
Classification of Renal Function Study Groups.........................................19 
Table 2: 
Investigational Product ..............................................................................30 
Table 3: 
Conditions for Permanent Discontinuation of Amgen Investigational 
Product and Other Protocol-required Therapies Due to Potential Hepatotoxicity .......72 
Table 4: 
Conditions for Withholding Amgen Investigational Product and Other 
Protocol-required Therapies Due to Potential Hepatotoxicity .....................................73 
  
Figure 1:  
Study Schema – Group 1 (Normal Renal Function) ..................................19 
Figure 2:  
Study Schema – Group 2 (ESRD Requiring Hemodialysis) .....................20 
Figure 3: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 1 – On 
Hemodialysis ................................................................................................................21 
Figure 4: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 2 – Off 
Hemodialysis ................................................................................................................21 
Figure 5:  
Sample Serious Adverse Event Report Form ............................................51 
Figure 6:  
Pregnancy Notification Form .....................................................................60 
Figure 7:  
Lactation Notification Form ......................................................................61 
 

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LIST OF ABBREVIATIONS 
Abbreviation Definition 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCA 
anti-neutrophil cytoplasmic autoantibody 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
AUCinf 
area under the plasma concentration-time curve from time zero to 
infinity 
AUClast 
area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration 
AUC0-48 
area under the plasma concentration-time curve from time zero to 
48 hours postdose 
BIL 
bilirubin 
BP 
blood pressure 
C5a 
complement component C5a 
C5aR 
complement 5a receptor 
CFR 
Code of Federal Regulations 
CLD 
hemodialysis clearance of drug (and metabolite) from plasma 
Cmax 
maximum observed plasma concentration 
CRF 
Case Report Form 
CRU 
Clinical Research Unit 
CTCAE 
Common Terminology Criteria for Adverse Events  
CV 
coefficient of variation 
CYP3A4 
cytochrome P450 3A4 
DILI 
drug-induced liver injury 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
ESRD 
end-stage renal disease 
FSH 
follicle-stimulating hormone 
fu 
fraction of unbound drug; reported as the arithmetic mean where 
measured at two time points 

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GCP 
Good Clinical Practice 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HD 
hemodialysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
MDRD 
Modification of Diet in Renal Disease 
OSF 
Other Safety Finding 
PK 
pharmacokinetic(s) 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
SS 
Special Situation 
TBL 
total bilirubin 
tmax 
time of the maximum observed concentration 
ULN 
upper limit of normal 

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1. INTRODUCTION 
Refer to the Investigator’s Brochure (IB)1, Prescribing Information2, and Summary of Product 
Characteristics3 for detailed information concerning the available pharmacology, toxicology, 
drug metabolism, clinical studies, and adverse event profile of the investigational medicinal 
product (IMP). 
1.1. 
Background 
Investigational Medicinal Product 
In the United States, TAVNEOS (formerly CCX168), hereafter referred to as avacopan, is 
currently approved as an adjunctive treatment of adult patients with severe active anti-neutrophil 
cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis and 
microscopic polyangiitis) in combination with standard therapy including glucocorticoids. 
Avacopan does not eliminate glucocorticoid use. Avacopan is also approved in the European 
Union for use in combination with a rituximab or cyclophosphamide regimen and is indicated for 
the treatment of adult patients with severe, active granulomatosis with polyangiitis or 
microscopic polyangiitis. Avacopan has also been approved in Canada, Great Britain, 
Switzerland, Japan, and the United Arab Emirates, and is under review in several other countries 
for marketing authorization.  
Avacopan is a highly potent and selective antagonist of the human complement 5a (C5a) receptor 
(C5aR), acting through competitive inhibition of the interaction between human C5aR and the 
anaphylatoxin complement component C5a; the latter is produced through activation of the 
complement cascade. As a result of its mechanism of action, avacopan reduces neutrophil 
activation, chemoattraction, and integrin expression. Avacopan inhibits vascular endothelial cell 
retraction and permeability, ameliorating the necrotizing vasculitis associated with 
ANCA-associated vasculitis.  
A summary of completed clinical studies for avacopan is provided in the IB (Table 6).1 
1.2. 
Pharmacokinetics 
The pharmacokinetics (PK) of avacopan has been evaluated in nine Phase 1 studies, two Phase 2 
studies, and one Phase 3 study in patients with ANCA-associated vasculitis.  
Following single oral administration in healthy subjects at doses ranging from 1 to 100 mg, 
avacopan was absorbed rapidly with maximum observed plasma concentration (Cmax) occurring 
approximately 1 to 2.5 hours postdose. Avacopan is primarily eliminated via extensive 
metabolism mediated through cytochrome P450 3A4 (CYP3A4) oxidation in the liver which 
results in the formation of and clearance of the major circulating metabolite, M1, a 
mono-hydroxylated product of avacopan. Following metabolism, the metabolites are primarily 
excreted into feces via bile. In the Phase 1 food-effect study, following a single oral dose of 
30 mg in the presence of a high-fat, high-calorie meal, avacopan exposures, area under the 

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plasma concentration-time curve (AUC), and Cmax, increased by approximately 72 and 8, 
respectively, and delayed the time of the maximum observed concentration (tmax) by 
approximately 4 hours (from 2.0 hours to 6.0 hours). The elimination half-lives of avacopan and 
M1 were 97.6 hours and 55.6 hours, respectively, under fed conditions. Following oral 
administration of avacopan 100 mg/400 Ci, about 77 and 10 of the radioactive dose was 
recovered in feces and urine, respectively, and 7 and 0.1 of the radioactive dose was 
recovered as unchanged avacopan in feces and urine, respectively. Avacopan and metabolite M1 
are more than 99.9 plasma-protein bound, primarily to albumin and 1-acid glycoprotein. A 
Phase 1 study in subjects with hepatic impairment evaluated the PK of avacopan and metabolite 
M1 following a single 
 dose for up to 18 days. Results from this study showed that plasma 
avacopan levels appeared to decline with a triphasic profile with a rapid early phase, followed by 
a longer phase, and finally a terminal phase with a half-life of about 200 to 400 hours in most 
subjects. Metabolite M1 appeared to decline in a biphasic manner with an elimination half-life of 
about 68 to 73 hours.2 
Previously, the impact of moderate renal impairment (estimated glomerular filtration rate [eGFR] 
between 30 and less than 60 mL/min/1.73 m2) and severe renal impairment (less than 
30 mL/min/1.73 m2) from patients with ANCA-associated vasculitis from Phase 2 and Phase 3 
studies relative to subjects with normal renal function (eGFR 90 mL/min/1.73 m2) from Phase 1 
studies were evaluated using population PK analysis. Results from population PK analyses 
demonstrated that avacopan and M1 exposures as assessed by Cmax and AUC were similar 
(20) across the different categories. Therefore, no dose adjustment for avacopan is needed 
based on renal function.1 
1.3. 
Study Rationale 
This study will be conducted to evaluate the PK of a single dose of avacopan in subjects with 
normal renal function and in subjects with end-stage renal disease (ESRD) requiring 
hemodialysis (HD). 
Results from this study will provide information on the safety, tolerability, and PK of avacopan 
and potentially guide dosing in patients with ESRD requiring HD. 
1.4. 
Benefit-risk Assessment 
The following benefit-risk assessment supports the conduct of this clinical study. Refer to the IB1 
for more information. 
1.4.1. 
Therapeutic Context 
1.4.1.1. 
Key Benefits 
Healthy and ESRD subjects in the current study will not receive any health benefit (beyond that 
of an assessment of their medical status) from participating in the study.  
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The secondary objective of the study is: 
 to evaluate the safety and tolerability of a single dose of avacopan in subjects with 
normal renal function and subjects with ESRD requiring HD. 
2.2. 
Endpoints 
2.2.1. 
Primary Endpoints 
The primary endpoints of the study are: 
 Cmax 
 area under the plasma concentration-time curve from time zero to time of last 
quantifiable concentration (AUClast) 
 area under the plasma concentration-time curve from time zero to infinity (AUCinf) 
 area under the plasma concentration-time curve from time zero to 48 hours (AUC0-48), or 
other partial area comparisons, as appropriate 
 HD clearance of drug (and metabolite) from plasma (CLD). 
2.2.2. 
Secondary Endpoints 
The secondary endpoints of the study are: 
 treatment-emergent adverse events 
 serious adverse events. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase 1, open-label, single-dose, parallel group study to evaluate the PK, safety, 
and tolerability of avacopan in subjects with normal renal function (Group 1) and subjects with 
ESRD requiring HD (Group 2). After informed consent is obtained, potential subjects will be 
screened to assess their eligibility to enter the study within 28 days prior to the first dose 
administration. 
Subjects in Group 1 (normal renal function) will be admitted into the Clinical Research Unit 
(CRU) on Day -1 and will be confined to the CRU until discharge on Day 8. Subjects in Group 1 
will receive a single 
dose of avacopan on Day 1 under fed conditions. Following 
discharge on Day 8, subjects will return to the CRU on Days 12, 15, and 18 (end of study [EOS] 
visit) for outpatient visits. An overview of the study schema for Group 1 is shown in Figure 1. 
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Subjects in Group 2 (ESRD requiring HD) will receive a single dose of 
 avacopan under 
fed conditions on Day 1 in each of the 2 treatment periods (Period 1/on HD and Period 2/off 
HD). An overview of the study schema for Group 2 is shown in Figure 2. 
Subjects in Group 2 will be admitted into the CRU on Period 1 Day -1 and will be confined to 
the CRU until discharge on Period 1 Day 8. Subjects in Group 2 Period 1 (on HD) will receive a 
single 
 dose of avacopan on Period 1 Day 1, 4 hours prior to the start of HD. Subjects will 
continue to receive HD on Days 3, 5, and 8 (prior to discharge). Following discharge on Day 8, 
subjects will return to the CRU on Period 1 Days 12, 15, and 18 for outpatient visits. The 
Group 2 Period 1 (on HD) schema is shown in Figure 3. 
Subjects in Group 2 will be re-admitted into the CRU for Period 2 Day -1 on the day of their HD. 
Period 1 Day 18 may occur on the same day as Period 2 Day -1. Subjects will receive a single 
 dose of avacopan on Period 2 Day 1 on an off-HD day (one day after the HD session on 
Period 2 Day -1). Subjects will continue to receive HD on Days 3, 5, and 7. Subjects will be 
confined to the CRU until discharge on Period 2 Day 8. Following discharge on Period 2 Day 8, 
subjects in Group 2 will return to the CRU on Period 2 Days 12, 15, and 18 (EOS) for outpatient 
visits. The Group 2 Period 2 (off-HD) schema is shown in Figure 4. There will be no washout 
between Day 18 of Period 1 and Check-in for Period 2 for subjects in Group 2. 
Additional plasma samples will be collected for estimation of plasma protein binding.  
The eGFR will be determined by the Modification of Diet in Renal Disease (MDRD) formula4: 
MDRD formula (mL/min/1.73m2)  175 x (serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) 
x (1.212 if African American) 
The renal function groups and eGFR values used to assign each subject to a renal function group 
are shown in Table 1. 
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Figure 3: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 1 – On 
Hemodialysis 
 
Abbreviations: HD  hemodialysis. 
Notes: Subjects will receive a single oral dose of avacopan 4 hours prior to start of HD session, under fed 
conditions. See Appendix 9 (Schedule of Assessments) for details on plasma pharmacokinetics, plasma protein 
binding sampling, and dialysate pharmacokinetics sampling. 
Figure 4: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 2 – Off 
Hemodialysis 
 
Abbreviations: EOS  end of study; ET  early termination; HD  hemodialysis. 
Notes: Subjects will receive a single oral dose of avacopan 1 day after the HD session. See Appendix 9 (Schedule of 
Assessments) for details on plasma pharmacokinetics and plasma protein binding sampling. 

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The total duration of study participation for each subject (from Screening through EOS visit) is 
anticipated to be approximately 7 weeks for Group 1 (normal renal function) and approximately 
9 weeks for Group 2 (ESRD requiring HD). 
The start of the study is defined as the date the first enrolled subject signs an Informed Consent 
Form (ICF). The point of enrollment occurs at the time of subject number allocation. The end of 
the study is defined as the date of the last subject’s last assessment (scheduled or unscheduled).  
A Schedule of Assessments is presented in Appendix 9. 
3.2. 
Discussion of Study Design 
This study will be open label because the study endpoints are not considered subjective. 
The PK results from prior Phase 1 studies demonstrated relatively linear and dose-proportional 
PK, suggesting that a single-dose study in subjects with renal impairment should adequately 
describe the PK of the drug. The safety and PK assessments are standard parameters for clinical 
studies in drug development. 
Plasma sampling is timed to sufficiently estimate PK parameters of avacopan exposure, based on 
characteristics of the concentration-time profile. 
This study will be conducted in subjects with normal renal function and in subjects with stable 
end-stage renal function who require HD. These subjects may have acceptable comorbid 
conditions in terms of safety and stability that are not anticipated to confound the study results. 
The subjects will be selected such that the mean and distribution of Group 1 is similar to the 
mean and distribution of subjects enrolled in Group 2 for age, sex, and body mass index, as far as 
possible. 
3.3. 
Selection of Doses in the Study 
Avacopan has been approved as an adjunctive treatment of adult subjects with severe active 
ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in 
combination with standard therapy including glucocorticoids. The recommended dosage is 
) twice daily, with food. 
For this study, a single dose of 
 is considered adequate to evaluate the pharmacokinetics 
and safety in subjects with normal renal function and in subjects with ESRD requiring HD. 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria prior to enrollment unless otherwise stated. 
Check-in with regards to inclusion criteria applies to Check-in on Period 1 Day -1 only. 
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1. Subject has provided informed consent before initiation of any study-specific 
activities or procedures. 
2. Male or female subjects, between 18 and 75 years of age (inclusive) at the time of 
Screening. 
3. Body mass index between 18 and 40 kg/m2 at the time of Screening. 
4. Subjects eligible for Group 1 (normal renal function) should be in good health, 
determined by no clinically significant findings from medical history, physical 
examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) as assessed by the 
Investigator (or designee). 
5. For subjects in Group 1 (normal renal function), systolic blood pressure (BP) 90 and 
150 mmHg and diastolic BP 50 and 100 mmHg, and pulse rate 40 and 110 
bpm at Screening. One repeat BP measurement will be allowed at Screening and 
Check-in. 
6. For subjects in Group 2 (ESRD requiring HD), vital signs, physical examinations, and 
12-lead ECGs (reporting heart rate, PR, QRS, QT, and QT interval corrected for heart 
rate using Fridericia’s method [QTcF]), including waveform, are normal or clinically 
acceptable to the Investigator, if outside the normal range. 
7. For subjects in Group 2 (ESRD requiring HD), laboratory test values (clinical 
chemistry and hematology) are consistent with the level of renal impairment and 
clinically acceptable to the Investigator. 
8. For subjects in Group 2 (ESRD requiring HD), nonhypertensive subjects or subjects 
with treated, stable hypertension, as defined by systolic BP not exceeding 170 mmHg 
and diastolic BP not exceeding 100 mmHg at Screening and Check-in. 
9. Eligible subjects will be classified based on established need for renal replacement 
therapy and eGFR, calculated using the MDRD formula. Assignment will be based on 
eGFR at Screening. 
a. Group 1 (normal renal function): eGFR 90 mL/min and no history of renal 
disease. 
b. Group 2 (ESRD requiring HD): eGFR 15 mL/min and receiving HD. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria prior to 
enrollment unless otherwise stated. Check-in with regards to exclusion criteria applies to 
Check-in on Period 1 Day -1 only. 

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All Subjects: 
10. History of uncontrolled or unstable cardiovascular, respiratory, hepatic, 
gastrointestinal, endocrine, hematopoietic, psychiatric, or neurological disease, 
defined as having been hospitalized within 28 days before Check-in, major surgery 
within 6 months before Check-in, or otherwise unstable in the judgment of the 
Investigator and/or Medical Monitor (e.g., risk of complications or adverse events 
unrelated to study participation), or evidence of rapidly deteriorating renal function. 
11. History or evidence, at Screening or Check-in, of clinically significant disorder, 
condition, or disease not otherwise excluded that, in the opinion of the Investigator 
(or designee), would pose a risk to subject safety or interfere with the study 
evaluation, procedures, or completion. 
12. Total white blood cell count is below the lower limit of normal at Screening or 
Check-in. 
13. Significant infection (in the judgment of the Investigator and/or Medical Monitor) 
within 28 days before Check-in. 
14. Prior infection with or exposure to tuberculosis, or travel to areas of endemic 
tuberculosis or endemic mycoses within the past 6 months. 
15. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase or 
alanine aminotransferase  the upper limit of normal for Group 1 (normal renal 
function) and 2 times the upper limit of normal for Group 2 (ESRD requiring HD). 
16. History or evidence, at Screening or Check-in, of poorly controlled diabetes 
(regardless of type), based on hemoglobin A1C of 10. 
17. Second-degree atrioventricular block or third-degree atrioventricular block at 
Screening or Check-in. 
18. Clinically significant hyperkalemia (defined by serum potassium concentration as 
5.5 mEq/L for Group 1 [normal renal function], 6 mEq/L for Group 2 [ESRD 
requiring HD]) at Screening or Check-in. Repeat testing and rescreening for screen 
failures will be permitted. 
19. Subjects who have a current, functioning organ transplant and/or are on 
immunosuppressants. 
20. Subjects on the national transplant list (United Network for Organ Sharing) at 
Screening who anticipate receiving an organ transplant within 4 months. 
21. Positive human immunodeficiency virus test. 
22. Positive hepatitis B or hepatitis C panel (including positive HBsAg and/or positive 
hepatitis C antibody) at Screening. Subjects whose results are compatible with prior 
hepatitis B infection (positive hepatitis B surface antibody, positive hepatitis B core 
antibody, or negative HBsAg) will be excluded. Subjects whose results are 

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compatible with prior hepatitis B vaccination (positive hepatitis B surface antibody, 
negative hepatitis B core antibody, negative HBsAg) may be included. 
23. History or evidence of clinically significant arrhythmia at Screening, including any 
clinically significant findings on the ECG taken at Check-in. 
24. History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, 
or duodenal ulceration, or bowel disease (including but not limited to peptic 
ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn’s disease, or irritable 
bowel syndrome); or a history of gastrointestinal surgery, other than uncomplicated 
appendectomy. 
25. History of hypersensitivity, intolerance, or allergy to avacopan or any of the 
excipients. 
26. Poor peripheral venous access. 
27. Currently taking a moderate or strong inducer of the CYP3A4 enzyme (e.g., 
carbamazepine, phenobarbital, phenytoin, or rifampin), or use of a strong CYP3A4 
inducer, within 5 half-lives or 14 days prior to Check-in (whichever is longer) and 
through EOS, unless deemed acceptable by the Investigator, Medical Monitor, and/or 
the Sponsor. 
28. Currently taking a moderate or strong inhibitor of the CYP3A4 enzyme (e.g., 
boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, 
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, 
saquinavir, telaprevir, telithromycin, or voriconazole), or use of a strong CYP3A4 
inhibitor, within 5 half-lives or 14 days prior to Check-in (whichever is longer) and 
through EOS, unless deemed acceptable by the Investigator, Medical Monitor, and/or 
the Sponsor. 
29. Use of any over-the-counter or prescription medications within 30 days or 5 half-lives 
(whichever is longer) before enrollment, with the below exceptions: 
a. Acetaminophen (paracetamol; up to 2 g/day) for analgesia will be allowed. 
b. Hormone replacement therapy (e.g., estrogen, thyroid treatments including 
levothyroxine [Synthroid, Levothroid, Levoxyl, and Unithroid], liothyronine 
[Cytomel], liotrix [Thyrolar], and natural thyroid [Armour Thyroid, Nature-throid, 
Westhroid]) will be allowed. 
c. Hormonal contraception will be allowed. 
d. Aside from strong inducers or inhibitors of CYP3A4, therapies for renal disease 
and treatments of comorbidities, such as hypertension, that have been stable for at 
least 3 months prior to study drug administration and deemed acceptable by the 
Investigator (or designee) and Medical Monitor to be given concurrently with 
avacopan during the study period are permitted. Minor adjustments in dose or 
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without significant change in clinical condition within the past 3 months are 
permitted. 
30. Consumption of foods and beverages containing poppy seeds, pomelos, or Seville 
oranges within 7 days prior to Check-in and consumption of foods and beverages 
containing grapefruit within 14 days prior to Check-in. 
31. All herbal medicines (e.g., St. John’s wort), vitamins, and supplements consumed by 
the subject within the 30 days prior to enrollment, unless deemed acceptable by the 
Investigator (or designee) and in consultation with the Sponsor. 
32. History of alcoholism or drug/chemical abuse within 1 year prior to Check-in. 
33. Alcohol consumption from 48 hours prior to Check-in. 
34. Regular alcohol consumption of 14 units per week for males and 7 units for 
females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 
5 oz (150 mL) wine. 
35. Significant use of tobacco- or nicotine-containing products (e.g., ½ pack of 
cigarettes per day) within 3 months prior to Check-in through EOS. 
36. Positive alcohol test at Check-in or positive drug screen (confirmed by repeat) at 
Screening or Check-in, that is not otherwise explained by permitted concomitant or 
prescription medications. Group 2 (ESRD requiring HD) subjects will be permitted 
on study if drug screen is positive for opiates or benzodiazepines. Subjects who 
screen positive for tetrahydrocannabinol/cannabinoids will be excluded. At Check-in, 
a positive alcohol test may not be repeated.  
37. Consumption of caffeine-containing foods and beverages within 48 hours prior to 
Check-in. 
38. Female subjects with a positive pregnancy test at Screening or Check-in. 
39. Female subjects lactating/breastfeeding or who plan to breastfeed during the study 
through 60 days after administration of investigational product. 
40. Unwilling to adhere to contraceptive requirements through 60 days after 
administration of investigational product. 
41. Unwilling to abstain from sperm donation and ovum donation through 60 days after 
administration of investigational product. 
42. Male subjects with a female partner of childbearing potential and not willing to 
inform his partner of his participation in this clinical study. 
43. Male subjects with a pregnant partner or partner planning to become pregnant who 
are unwilling to practice sexual abstinence or use contraception while the subject is 
participating in the study from Check-in until 60 days after administration of 
investigational product. 

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44. Subject has received a dose of an investigational drug within the past 30 days or 
5 half-lives, whichever is longer, prior to Check-in. 
45. Have previously completed or withdrawn from this study or any other study 
investigating avacopan, or have previously received the investigational product.  
46. Donation of blood from 90 days prior to Check-in, plasma from 2 weeks prior to 
Check-in, or platelets from 6 weeks prior to Check-in. 
47. Unwilling to abide with study restrictions. 
48. Subjects who, in the opinion of the Investigator (or designee), should not participate 
in this study. 
Subjects in Group 1 (normal renal function) are excluded if: 
49. History of malignancy of any type, with the exception of the following: in situ 
cervical cancer or surgically excised non-melanomatous skin cancers more than 
5 years before receiving avacopan. 
50. A QTcF 450 msec in males or 470 msec in females or history/evidence of long QT 
syndrome at Screening or Check-in. 
51. A history of renal disease or renal injury as indicated by medical history or an 
abnormal renal function profile at Screening or Check-in. 
Subjects in Group 2 (ESRD requiring HD) are excluded if: 
52. Child-Pugh Class C, indicating severe hepatic impairment assessed at Screening and 
Check-in (Appendix 10). Child-Pugh will only be evaluated for subjects deemed to 
have active liver disease by the Investigator (or designee). 
53. Active malignancy of any type. Subjects with a history of malignancy that has been 
eradicated with supporting medical documentation indicating that there is no residual 
malignancy detected in the past 2 years will be allowed.  
54. A change in disease status within 30 days of Screening, as documented by the 
subject’s medical history, deemed clinically significant by the Investigator. 
55. A QTcF 470 msec in males or 480 msec in females. 
4.3. 
Screen Failures and Rescreening 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently enrolled in the study because they do not meet eligibility requirements. A minimal 
set of screen failure information may be collected that includes demography, screen failure 
details, eligibility criteria, medical history, prior therapies, and any serious adverse events. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened only once.  

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terminate the Investigator's participation in the study according to the Clinical Trial Agreement. 
The Investigator is to notify the Institutional Review Board (IRB) in writing of the study's 
completion or early termination and send a copy of the notification to the Sponsor. The Sponsor 
reserves the unilateral right, at its sole discretion, to determine whether to supply investigational 
product and by what mechanism, after termination of the study. 
In addition, the study may be terminated by the Sponsor at any time and for any reason. If the 
Sponsor decides to terminate the study, they will inform the Investigator as soon as possible. 
4.7. 
Discontinuation of Study Treatment (Group 2 only) 
Subjects (or a legally acceptable representative) can decline to continue receiving investigational 
product and/or other protocol-required therapies or study procedures at any time during the study 
but continue participation in the study. If this occurs, the Investigator is to discuss with the 
subject the appropriate processes for discontinuation from investigational product or other 
protocol-required therapies and must discuss with the subject the possibilities for continuation of 
the Schedule of Assessments (Appendix 9) including different options of follow-up (e.g., in 
person, by phone/mail, through family/friends, in correspondence/communication with other 
treating physicians, from the review of medical records) and collection of data, including 
endpoints, Adverse Events, Serious Adverse Events and must document this decision in the 
subject’s medical records. Subjects who have discontinued investigational product and/or other 
protocol-required therapies or study procedures should not be automatically removed from the 
study. Whenever safe and feasible, it is imperative that subjects remain on study to ensure safety 
surveillance and/or collection of outcome data. 
Reasons for removal from protocol-required investigational product(s) or procedural assessments 
include any of the following: 
 
Decision by Sponsor 
 
Lost to follow-up 
 
Death 
 
Adverse event 
 
Subject request 
 
Ineligibility determined 
 
Protocol deviation 
 
Noncompliance 
 
Requirement for alternative therapy 
 
Pregnancy 
 
Protocol-specified criteria 

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5. STUDY TREATMENTS 
Study treatment is defined as any investigational product, non-investigational product, placebo, 
or medical device intended to be administered to a study subject according to the study protocol. 
Note that in several countries, investigational product and non-investigational product are 
referred to as investigational medicinal product and non-investigational medicinal product, 
respectively. 
5.1. 
Investigational Product 
The IMP will be supplied by the Sponsor. Detailed information regarding the storage, 
preparation, destruction, and administration of IMP will be provided.  
All supplies of investigational product, both bulk and subject-specific, will be stored in 
accordance with the manufacturer’s instructions or pharmacy instructions. Until dispensed to the 
subjects, the investigational and non-investigational products will be stored at the study site in a 
location that is locked with restricted access. 
The IMP will be stored according to the instructions on the label at the CRU. 
Table 2: 
Investigational Product 
Study Treatment Name 
Investigational Medicinal Product: 
Avacopan 
Unit Strength and Formulation 
 Immediate Release Hard Gelatin Capsule 
Dose 
 
Route of Administration 
Oral 
Accountability 
The quantity administered, date administered, and lot 
number of investigational product are to be recorded on the 
appropriate Case Report Form.  
Dosing Instructions 
The Investigator/designee will administer the treatment after 
the completion of all predose procedures, under fed 
conditions. A standardized hemodialysis-friendly 
standardized meal will be provided to all subjects on Day 1. 
The dose should be taken within 30 minutes of the start of 
the meal. 
 should be taken with 
approximately 8 ounces (240 mL) of water. Capsules should 
not be broken or chewed. 
Except as part of the dose administration, subjects will restrict their consumption of water for 
1 hour prior to dosing and for 1 hour after dosing; at all other times during the study, subjects 
may consume water as desired. Subjects will fast for at least 4 hours postdose. 
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Subjects will be dosed while standing and will not be permitted to lie supine for 2 hours after 
administration of IMP, except as necessitated by the occurrence of an adverse event(s) and/or 
study procedures. 
5.2. 
Investigational Product Administration 
Subjects in Group 1 will have 1 dose administration each of 
 of avacopan and subjects in 
Group 2 will have two dose administrations each of 
 of avacopan. Subjects will be dosed 
in the order that they were enrolled. Subjects will receive all doses under supervision of the site 
staff. 
5.3. 
Treatment of Overdose 
For this study, any dose of avacopan greater than 
 will be considered an overdose. The 
effects of overdose of avacopan are not known. In case of overdose, consultation with the 
Medical Monitor is recommended for prompt reporting of clinically apparent or laboratory 
adverse events possibly related to overdosage, and to discuss further management of the subject. 
5.3.1. 
Medical Devices  
No investigational medical devices will be used in this study. 
Other non-investigational medical devices may be used in the conduct of this study as part of 
standard care. Non-Amgen non-investigational medical devices (e.g., syringes, sterile needles), 
that are commercially available are not usually provided or reimbursed by the Sponsor (except, 
for example, if required by local regulation). The Investigator will be responsible for obtaining 
supplies of these devices. 
5.3.2. 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
drug, combination product, or device after it is released for distribution to market or clinic by 
either (1) Amgen or (2) distributors or partners for whom Amgen manufactures the material. 
This includes all components distributed with the drug, such as packaging drug containers, 
delivery systems, labeling, and inserts. 
This includes any investigational/non-investigational product(s), provisioned and/or 
repackaged/modified by Amgen.  
Any product complaint(s) associated with an investigational product(s) supplied by Amgen are to 
be reported. 
5.4. 
Randomization 
This is a nonrandomized study. The study has a fixed treatment sequence. 
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5.5. 
Blinding 
This is an open-label study. 
5.6. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance:  
 When subjects are dosed at the site, they will receive avacopan directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded on the 
eCRF.  
 Immediately after dose administration, visual inspection of the mouth and hands will be 
performed for each subject. 
 At each dosing occasion, a predose and postdose inventory of IMP will be performed. 
5.7. 
Drug Accountability 
The Investigator (or designee) will maintain an accurate record of the receipt of avacopan 
capsules received. In addition, an accurate drug disposition record will be kept, specifying the 
amount dispensed to each subject and the date of dispensing. This drug accountability record will 
be available for inspection at any time. At the completion of the study, the original drug 
accountability record will be available for review by the Sponsor upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused assembled 
unit doses will be retained until completion of the study. 
At the completion of the study, all unused avacopan will be returned to the Sponsor, retained at 
the study site, or disposed of by the study site, per the Sponsor’s written instructions. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects with normal renal function will refrain from use of any prescription or nonprescription 
medications/products during the study until the EOS visit, unless the Investigator (or designee) 
and/or Sponsor have given their prior consent.  
For renal-impaired subjects, treatment with chronic stable medications (for at least 3 months 
prior to study drug administration with the exceptions of minor changes in dose or formulation 
without change in clinical condition) necessary for maintaining the clinical status of the subject 
will be permitted if prescribed by the subject’s personal physician and approved by the Medical 
Monitor and Investigator, in consultation with the Sponsor as needed. Except for concomitant 

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therapies associated with HD sessions, administration of medications should be withheld for at 
least 4 hours after study drug administration as clinically appropriate, unless needed for 
treatment of an adverse event, at the discretion of the Investigator. Throughout the study, 
Investigators may prescribe any concomitant medications or treatments deemed necessary to 
provide adequate supportive care while avoiding those listed in the exclusion criteria. 
Acetaminophen (paracetamol) (2 g/day); hormone replacement therapy (e.g., estrogen and 
thyroid treatments including levothyroxine [Synthroid, Levothroid, Levoxyl, Unithroid], 
liothyronine [Cytomel], Liotrix [Thyrolar], and natural thyroid [Armour Thyroid, Nature-throid, 
Westhroid]); or oral, implantable, transdermal, injectable, or intrauterine contraceptives are 
acceptable concomitant medications. The administration of any other concomitant medications 
during the study is prohibited without prior approval of the Investigator (or designee), unless its 
use is deemed necessary for treatment of an adverse event/serious adverse event. Any medication 
taken by a subject during the course of the study and the reason for its use will be documented in 
the source data. 
6.2. 
Diet 
Subjects will be fasted overnight (at least 8 hours) before collection of blood samples for clinical 
laboratory evaluations. While confined at the study site, subjects will receive a diet provided by 
the site at scheduled times that do not conflict with other study-related activities. No outside food 
or beverage will be permitted during confinement. 
On dosing days (Day 1 for Group 1 and Day 1 of Periods 1 and 2 for Group 2), subjects will 
receive a standardized breakfast prior to study drug administration. The standardized breakfast 
will include approximately 215 fat calories, approximately 320 carbohydrate calories, 
approximately 125 protein calories, and approximately 1220 mg of sodium. 
Refer to Section 5 and Table 2 for diet requirements/restrictions on applicable days of study 
treatment and/or PK assessments. 
Foods and beverages containing poppy seeds, pomelos, or Seville oranges will not be allowed 
from 7 days prior to Check-in until EOS visit. Foods and beverages containing grapefruit will not 
be allowed from 14 days prior to Check-in until EOS visit. 
Caffeine-containing foods and beverages will not be allowed from 48 hours before Check-in 
until EOS visit. 
Consumption of alcohol will not be permitted from 48 hours prior to Check-in until EOS visit. 
6.3. 
Smoking 
Subjects will not be permitted significant use of tobacco- or nicotine-containing products (e.g., 
 ½ pack of cigarettes per day) within 3 months prior to Check-in through EOS. 

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6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before Check-in until the 
EOS visit. Subjects will otherwise maintain their normal level of physical activity during this 
time (i.e., will not begin a new exercise program nor participate in any unusually strenuous 
physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 90 days prior to Check-in, plasma 
from 2 weeks prior to Check-in, and platelets from 6 weeks prior to Check-in until 3 months 
after the EOS visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving consideration to appropriate posture conditions, practical restrictions, and 
the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. Unless otherwise 
specified in the Schedule of Assessments, the order of priority for scheduling procedures around 
a timepoint is: 
 predose safety assessments 
 
predose/trough PK blood samples 
 
dosing 
 
PK blood samples (postdose) 
 
postdose safety assessments (ECGs will be scheduled before vital signs measurements) 
 
any other procedures. 
Where activities at a given timepoint coincide, consideration must be given to ensure that the 
following order of activities is maintained: ECGs, vital signs, and safety laboratory assessments. 
7.1. 
Pharmacokinetic Assessments 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples will be collected by venipuncture or cannulation at the times indicated in the 
Schedule of Assessments in Appendix 9. Arterial and venous PK samples may be collected from 
the HD catheter or arteriovenous fistula as appropriate. 
Dialysate samples will be collected as specified in Appendix 9. Procedures for collection, 
processing, and shipping of PK blood samples will be detailed in a separate document.  

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For Group 2 Period 1, a sample of dialysate will be collected on Day 1 at 0.5, 1, 2, and 3 hours 
after the start of HD and after HD is complete for drug concentration analysis. The entire 
dialysate volume, blood flow, and dialysate flow during HD will be recorded for each timepoint, 
and the make and model of the dialyzer will be recorded. 
Any blood sample collected according to the Schedule of Assessments (Appendix 9) can be 
analyzed for any of the tests outlined in the protocol and for any tests necessary to minimize 
risks to study subjects. This includes testing to ensure analytical methods produce reliable and 
valid data throughout the course of the study. This can also include, but is not limited to, 
investigation of unexpected results, incurred sample reanalysis, and analyses for method transfer 
and comparability.  
7.1.2. 
Analytical Methodology 
Plasma concentrations of avacopan and M1 metabolite will be determined using validated 
analytical procedures. Dialysate concentrations of avacopan and protein binding assessments will 
be determined using qualified methods. Specifics of the analytical method will be provided in a 
separate document. 
7.2. 
Safety and Tolerability Assessments 
7.2.1. 
Adverse Events and Serious Adverse Events: Time period and Frequency for 
Collecting and Reporting Safety Event Information 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
Adverse Events and Serious Adverse Events are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF to EOS. 
Subjects will be observed for any signs or symptoms and asked about their condition by open 
questioning, such as “How have you been feeling since you were last asked?”, at least once each 
day while resident at the study site and at each study visit. Subjects will also be encouraged to 
spontaneously report Adverse Events and Serious Adverse Events occurring at any other time 
during the study. 
Adverse Events 
The adverse event grading scale to be used in this study is described in Appendix 1. 
The Investigator is responsible for ensuring that all adverse events observed by the Investigator 
or reported by the subject that occur after first dose of investigational product through the 
30 days after the last day of the dosing interval of investigational product, whichever is later are 
reported using the Events Case Report Form (CRF). 

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Serious Adverse Events 
The Investigator is responsible for ensuring that all serious adverse events observed by the 
Investigator or reported by the subject that occur after signing of the informed consent through 
30 days after dosing of investigational product or EOS visit, whichever is later, are reported 
using the appropriate eCRF and reported on the paper-based Serious Adverse Event Report Form 
(described in Appendix 1). 
All serious adverse events will be collected, recorded, and reported to the Sponsor within 
24 hours of the Investigator’s knowledge of the event. The Investigator will submit any updated 
Serious Adverse Event data to the Sponsor within 24 hours of it being available. 
Since the criteria of the Common Terminology Criteria for Adverse Events (CTCAE) grading 
scale differs from the regulatory criteria for serious adverse events, if adverse events correspond 
to Grade 4 CTCAE toxicity grading scale criteria (e.g., laboratory abnormality reported as Grade 
4 without manifestation of life-threatening status), it will be left to the Investigator’s judgment to 
also report these abnormalities as serious adverse events. For any adverse event that applies to 
this situation, comprehensive documentation of the event’s severity must be recorded in the 
subject medical records. 
Serious Adverse Events After the Protocol-Required Reporting Period  
After EOS, there is no requirement to actively monitor study subjects after the study has ended 
with regards to study subjects treated by the Investigator. However, if the Investigator becomes 
aware of serious adverse events (regardless of causality), then these serious adverse events will 
be reported to Amgen within 24 hours following the Investigator’s awareness of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the Sponsor’s safety database as clinical trial cases and handled accordingly 
based on relationship to investigational product.  
If further safety-related data is needed to fulfill any regulatory reporting requirements for a 
reportable event, then additional information may need to be collected from the subject’s records 
after the subject ends the study. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious adverse 
events. Open-ended and non-leading verbal questioning of the subject is the preferred method to 
inquire about adverse event occurrence. 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial adverse event/serious adverse event report, the Investigator is required to 
proactively follow each subject at subsequent visits/contacts. All adverse events and serious 

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adverse events will be followed, where possible, until resolution, stabilization, until the event is 
otherwise explained, or the subject is Lost to Follow-up. This will be completed at the 
Investigator’s (or designee’s) discretion. 
All new information for previously reported serious adverse events must be sent to Amgen 
within 24 hours following knowledge of the new information. If specifically requested, the 
Investigator may need to provide additional follow-up information, such as discharge summaries, 
medical records, or extracts from the medical records. Information provided about the serious 
adverse event must be consistent with that recorded on the eCRF. 
Regulatory Reporting Requirements for Serious Adverse Events 
If the subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to the Sponsor. 
Prompt notification by the Investigator to the Sponsor of serious adverse events is essential so 
that legal obligations and ethical responsibilities towards the safety of subjects and the safety of a 
study treatment under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRBs/Independent Ethics Committees, and Investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
Amgen will prepare a single Development Safety Update Report (also referred to as Annual 
Safety Report in the European Union) for the Amgen Investigational Product. To ensure that 
consolidated safety information for the study is provided, this single Development Safety Update 
Report will also include appropriate information on any other investigational products used in 
the clinical study, if applicable. 
An Investigator who receives an individual safety report describing a serious adverse event or 
other specific safety information (e.g., summary or listing of serious adverse events) from the 
Sponsor will file it along with the IB and will notify the IRB, if appropriate according to local 
requirements. 
Safety Monitoring Plan 
Subject safety will be routinely monitored as defined in the Sponsor’s safety surveillance and 
signal management processes. 

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Other Safety Findings/Special Situations 
Medication errors, misuse or abuse of the investigational product is subject to the same reporting 
obligation as adverse events. Therefore, the following procedures must be followed:  
 All medication errors, misuse, or abuse of the investigational product, whether or not the 
Other Safety Finding (OSF)/Special Situation (SS) is accompanied by a non-serious 
adverse event or a serious adverse event, as determined by the Investigator, the OSF/SS 
must be collected and recorded on the OSF/SS CRF. 
 If there are any resulting clinical signs, symptoms, or sequelae, the corresponding non-
serious adverse event or serious adverse event must also be collected and recorded on the 
Events CRF.  
 All medication errors, misuse, or abuse when associated with a serious adverse event 
must also be reported to Amgen or designee immediately and no later than 24 hours of 
the Investigator’s awareness of the OSF/SS - medication error, misuse, or abuse by 
submitting Serious Adverse Event Report Form. 
Further details and definitions regarding OSF/ SS - medication errors, misuse, and abuse, can be 
found in Appendix 1. 
Pregnancy and Lactation 
Details of all pregnancies and/or lactation in female subjects and, if indicated, female partners of 
male subjects will be collected after the start of study treatment and until 60 days after dosing of 
investigational product. 
If a pregnancy is reported, the Investigator is to inform Amgen immediately and no later than 
24 hours of learning of the pregnancy and/or lactation and is to follow the procedures outlined in 
Appendix 4. Amgen Global Patient Safety will follow-up with the Investigator regarding 
additional information that may be requested. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Appendix 4. 
Pregnancy Testing 
A highly sensitive (urine or serum) pregnancy test should be completed at screening and within 
7 days of initiation of investigational product for females of childbearing potential.  
Note: Females who have undergone a bilateral tubal ligation/occlusion should have pregnancy 
testing per protocol requirements. (If a female subject, or the partner of a male subject, becomes 

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pregnant it must be reported on the Pregnancy Notification Form, see Figure 6). Refer to 
Appendix 3 for contraceptive requirements. 
A pregnancy test will be performed at the end of the study. 
Additional on-treatment pregnancy testing may be performed at the Investigator’s discretion or 
as required per local laws and regulations.  
7.2.2. 
Clinical Laboratory Evaluations 
Blood samples will be collected for clinical laboratory evaluations (including clinical chemistry, 
hematology, and serology) at the times indicated in the Schedule of Assessments in Appendix 9. 
Urine samples will be collected for Group 1 only for clinical laboratory evaluations (including 
clinical chemistry, hematology, urinalysis, and serology) at the times indicated in the Schedule of 
Assessments in Appendix 9. Clinical laboratory evaluations are listed in Appendix 2. 
The Investigator is responsible for reviewing laboratory test results and recording any clinically 
relevant changes occurring during the study in CRF/eCRF. The Investigator must determine 
whether an abnormal value in an individual study subject represents a clinically significant 
change from the subject’s baseline values. In general, abnormal laboratory findings without 
clinical significance (based on the Investigator’s judgment) are not to be recorded as adverse 
events. However, laboratory value changes that require treatment or adjustment in current 
therapy are considered adverse events. Where applicable, clinical sequelae (not the laboratory 
abnormality) are to be recorded as the adverse event. 
Subjects in Group 1 will provide urine samples for drugs of abuse screen and will undergo an 
alcohol breath test at the times indicated in the Schedule of Assessments in Appendix 9. Subjects 
in Group 2 will provide a blood or saliva sample for drugs of abuse screen and will undergo an 
alcohol breath test at the times indicated in the Schedule of Assessments in Appendix 9. For all 
female subjects, a pregnancy test and follicle-stimulating hormone (FSH) screen for 
postmenopausal women will be performed at the times indicated in the Schedule of Assessments 
in Appendix 9.  
An Investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.2.3. 
Vital Signs 
Seated or supine BP, seated or supine pulse rate, respiratory rate, and oral body temperature will 
be assessed at the times indicated in the Schedule of Assessments in Appendix 9. Vital signs may 
also be performed at other times if judged to be clinically appropriate. 
All measurements will be performed singly and repeated once if outside the relevant clinical 
reference range. 

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Subjects must be seated or supine for at least 5 minutes before BP and pulse rate measurements. 
When vital signs are scheduled at the same time as blood draws, the blood draws will be 
obtained at the scheduled timepoint, and the vitals will be obtained as close to the scheduled 
blood draw as possible, but prior to the blood draw. 
Vital signs for subjects will be taken consistently for each subject in either the seated or supine 
position. If the subject is unable to be in the supine position, the subject should be in the most 
recumbent position possible. The position selected for a subject should be the same that is used 
throughout the study and documented on the vital signs eCRF. 
7.2.4. 
12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at least 
5 minutes at the times indicated in the Schedule of Assessments in Appendix 9. Single 12-lead 
ECGs will be repeated twice, and an average taken of the 3 readings, if either of the following 
criteria apply: 
 QTcF is 500 ms 
 QTcF change from the baseline (predose) is 60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically appropriate. 
The Investigator (or designee) will perform a clinical assessment of each 12-lead ECG and 
initiate further work-up or intervention as necessary. 
7.2.5. 
Physical Examination 
Physical examination will be performed and will include a neurological examination (breast, 
rectal, and genital examination are not required). Neurologic examination will include evaluation 
of mental status/cognition/mood/affect, gross and fine motor, sensory, cranial nerves, 
coordination, and deep tendon reflexes. Physical examination findings should be recorded on the 
appropriate CRF (e.g., medical history, treatment-emergent adverse event). Physical 
examinations will be performed at the timepoints specified in the Schedule of Assessments in 
Appendix 9. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
The sample size for this study is based on studies of similar design and is considered adequate 
for evaluation of the study objectives. 
Approximately 12 subjects are planned to be enrolled in this study. Approximately 6 subjects 
will be enrolled in each group. 

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8.2. 
Analysis Populations 
8.2.1. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of avacopan and have 
evaluable PK data. A subject may be excluded from the PK summary statistics and statistical 
analysis if the subject has an adverse event of vomiting that occurs at or before 2 times median 
time to maximum concentration or diarrhea within 24 hours of dosing.  
8.2.2. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of avacopan and have 
at least 1 postdose safety assessment. 
If a subject has a serious adverse event prior to dosing, reporting of the serious adverse event will 
be included with the safety population. 
8.3. 
Pharmacokinetic Analyses 
Arithmetic mean, coefficient of variation (CV), standard deviation, median, minimum, 
maximum, and number of observations will be calculated for the PK parameters for each renal 
function group. Geometric mean and geometric CV will be provided for all PK parameters 
except tmax. Median, minimum, maximum, and number of observations will be calculated for 
tmax. 
The primary statistical analysis will estimate the relationship between the PK of avacopan and 
eGFR estimated by the MDRD equation. In addition, a relationship between the PK of M1 and 
the eGFR may also be evaluated. 
The PK parameters Cmax, tmax, apparent plasma terminal elimination half-life, AUCinf, AUC0-48, 
AUClast, apparent clearance (CL/F), fraction of unbound drug (fu), apparent volume of 
distribution (Vz/F), extraction ratio for HD (ERD), and CLD will be determined, as appropriate, 
by using noncompartmental methods. Additional PK parameters may be determined as 
appropriate. 
Ratios (test/reference) for the model-estimated Cmax, AUC0-48 (calculated for Group 2 Period 2), 
and AUCinf (test) relative to the group with normal renal function (reference) will be generated, 
along with 90 confidence intervals. 
For subjects in Group 2, the PK parameters Cmax, tmax, AUC0-48, and AUC0-last will be determined 
by using noncompartmental methods for doses administered. For subjects in Group 2 Period 1, a 
sample of dialysate will be collected on Day 1 at 0.5, 1, 2, and 3 hours. In addition, to support 
determination of avacopan clearance by HD, AUClast will be determined from the arterial and 
venous plasma samples during HD (for Group 2 Period 1). The ratios (test/reference) of central 

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values and 90 CIs will be calculated for log-transformed Cmax and AUC values on HD day 
(Group 2 Period 1, test) compared to non-HD day (Group 2 Period 2, reference). 
Specific details will be presented in the Statistical Analysis Plan for this study. 
8.4. 
Safety Analysis 
The number and percentage of subjects reporting any adverse events will be tabulated by 
Medical Dictionary for Regulatory Activities system organ class and preferred term. Tables of 
fatal adverse events, serious adverse events, adverse events leading to withdrawal from 
investigational product, and treatment-emergent adverse events will also be provided. Subject-
level data may be provided instead of tables if the subject incidence is low. 
Clinical laboratory tests, ECG, and vital signs will be summarized. 
8.5. 
Interim Analysis 
No interim analyses are planned for this study.  
9. REFERENCES 
1. Amgen. Avacopan – Current Investigator’s Brochure.  
2. TAVNEOS (avacopan) capsules, for oral use. Highlights of Prescribing Information.  
3. Tavneos (Avacopan). Summary of Product Characteristics. Vifor Fresenius Medical Care 
Renal Pharma UK Ltd. 30 Aug 2023.  
4. US Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research. 2024. Guidance for industry: Pharmacokinetics in Patients 
with Impaired Renal Function - Study Design, Data Analysis, and Impact on Dosing. 
 

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10. APPENDICES 

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Other Safety Findings/Special Situations: Medication Errors, Misuse or Abuse 
All medication errors, misuse or abuse of the investigational product are subject to the 
same reporting obligation as adverse events and must be collected and recorded on the 
Other Safety Findings (OSF)/Special Situations (SS) case report form (CRF). If there 
are any resulting clinical signs, symptoms or sequelae, the corresponding non-serious 
adverse event and serious adverse event must also be collected and recorded on the 
Events CRF.   
All medication errors, misuse, or abuse when associated with a serious adverse event 
must also be reported to Amgen or designee immediately and no later than 24 hours of 
Investigator’s awareness of the OSF/SS - medication error, misuse, or abuse by 
submitting the paper-based Serious Adverse Event Report Form. 
Other Safety 
Finding/Special Situation 
Collected and Recorded 
on the Other Safety 
Findings (OSF)/Special 
Situations (SS) Case 
Report Form (CRF)  
Primary Reporting 
Method:  
Reported/submitted on 
the paper-based Serious 
Adverse Event Report 
Form to Amgen or 
designee immediately and 
no later than 24 hours of 
Investigator’s awareness 
Medication Error 
All (regardless of 
whether associated with 
an adverse event/serious 
adverse event) 
Only if associated with a 
serious adverse event  
Misuse 
All (regardless of 
whether associated with 
an adverse event/serious 
adverse event)  
Only if associated with a 
serious adverse event  
Abuse 
All (regardless of 
whether associated with 
an adverse event/serious 
adverse event) 
Only if associated with a 
serious adverse event  
 
 
Medication Error: A medication error is an unintended failure 
in the drug treatment process that leads to, or has the potential 
to lead to harm to the subject (e.g., mistake in the process of 

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medical records. In this case, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records before 
submission to the Sponsor. 
 The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the adverse event/serious 
adverse event.  

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Figure 5:  
Sample Serious Adverse Event Report Form  
 

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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis – Group 1 only: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Blood urea nitrogen 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate 
Potassium  
Sodium  
Total bilirubina 
Total CO2 (may be measured as 
bicarbonate) 
Total protein 
Uric acid 
Hematocrit  
Hemoglobin  
Hemoglobin A1Cb 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell (RBC) count 
RBC distribution width 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Bilirubin 
Blood 
Color and appearance 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination (if 
protein, leukocyte esterase, 
nitrite, or blood is positive) 
Serologyc: 
Drug screenb: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency virus 
(HIV-1 and HIV-2) antibodies 
and p24 antigen 
Including but not limited to:  
Amphetamines/ 
methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol/ 
cannabinoids 
Alcohol breath testd  
Follicle-stimulating hormone 
(postmenopausal females only)c 
Serum pregnancy test (human 
chorionic gonadotropin)e 
Urine pregnancy teste 
Other Tests: 
Coagulation panelb: 
Hepatotoxicity
only: 
International 
normalized 
ratio (INR)f 
Estimated 
glomerular 
filtration rate 
(eGFR)g 
International normalized ratio 
(INR) 
Prothrombin time (PT) 
Activated partial thromboplastin 
time (aPTT) 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated. 
b Only analyzed at Screening and Check-in. 
c Only analyzed at Screening. 
d Alcohol breath test performed at Check-in only. Matrix for drug screen will be flexible, depending on the renal impairment 
status of the subject. 
e Performed in serum at Screening and in urine at all other times for females in Group 1. A positive urine pregnancy test will be 
confirmed with a serum pregnancy test. Serum pregnancy test will be done at all timepoints for subjects in Group 2 (end-stage 
renal disease [ESRD]). 
f International normalized ratio will be retested if hepatotoxicity is suspected. 
g Estimated glomerular filtration rate will be calculated by the Modification of Diet in Renal Disease (MDRD) equation. 
  MDRD formula (mL/min/1.73 m2)  175 x (serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.212 if African-American) 

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Appendix 3: Contraception Requirements 
All subjects must receive pregnancy prevention counseling and be advised of the risk to the fetus 
if they conceive a child during treatment and for 60 days after administration of the 
investigational product. 
Additional medications given during the study may alter the contraceptive requirements. The 
Investigator must discuss these contraceptive changes with the subject. 
Definitions Women of Childbearing Potential: premenopausal females who are anatomically 
and physiologically capable of becoming pregnant following menarche.  
Women of Non-Child-Bearing Potential: 
1. Surgically sterile: females who are permanently sterile via hysterectomy, bilateral 
salpingectomy, and/or bilateral oophorectomy by reported medical history and/or 
medical records. Surgical sterilization to have occurred a minimum of 6 weeks, or at 
the Investigator’s discretion, prior to Screening.  
2. Postmenopausal: Females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating hormone 
levels of  40 mIU/mL. The amenorrhea should not be induced by a medical 
condition such as anorexia nervosa, hypothyroid disease, or polycystic ovarian 
disease, or by extreme exercise. It should not be due to concomitant medications that 
may have induced the amenorrhea such as oral contraceptives, hormones, 
gonadotropin-releasing hormones, anti-estrogens, or selective estrogen receptor 
modulators.  
Fertile male: males are considered fertile after puberty.  
Contraception Requirements 
Female Subjects  
Female subjects who are of nonchildbearing potential will not be required to use contraception. 
Female subjects of childbearing potential must be willing to use 2 methods (1 primary and 
1 secondary method) of birth control from the time of signing the Informed Consent Form (ICF) 
until 60 days after administration of the investigational product.  
Primary methods of contraception include:  
 hormonal injection (as prescribed)  
 combined oral contraceptive pill or progestin/progestogen-only pill associated with 
inhibition of ovulation (as prescribed) without supplementary iron (i.e. Loestrin Fe, Junel 
Fe, and Lo Loestrin Fe are prohibited) 
 combined hormonal patch (as prescribed)  

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 combined hormonal vaginal ring (as prescribed)  
 surgical method performed at least 3 months prior to the Screening visit:  
o Bilateral tubal ligation with confirmation of surgical success 
o Regulatory approved method of hysteroscopic bilateral tubal occlusion with 
confirmation of occlusion of the fallopian tubes 
 hormonal implant  
 hormonal or non-hormonal intrauterine device  
 vasectomized male partner (sterilization performed at least 90 days prior to the Screening 
visit, with verbal confirmation of surgical success, and the sole partner for the female 
subject).  
Secondary (barrier) methods of contraception include:  
 male condom with spermicide  
 female condom with spermicide  
 over-the-counter sponge with spermicide  
 cervical cap with spermicide (as prescribed)  
 diaphragm with spermicide (as prescribed).  
Female subjects should refrain from donation of ova from Check-in (Day -1) until 60 days after 
administration of the investigational product. 
Male Subjects:  
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (i.e., male condom with spermicide) in addition to a 
second method of acceptable contraception by female partner from Check-in until 60 days after 
administration of investigational product. Acceptable methods of contraception for female 
partners include:  
 hormonal injection  
 combined oral contraceptive pill or progestin/progestogen-only pill  
 combined hormonal patch  
 combined hormonal vaginal ring  
 surgical method (bilateral tubal ligation or regulatory approved method of hysteroscopic 
bilateral tubal occlusion)  
 hormonal implant  
 hormonal or non-hormonal intrauterine device  

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 over-the-counter sponge with spermicide  
 cervical cap with spermicide  
 diaphragm with spermicide.  
Male subjects are required to refrain from donation of sperm from Check-in until 60 days after 
administration of the investigational product.  
Sexual Abstinence  
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of 
risk associated with the study treatments) is an acceptable method of contraception. The 
reliability of sexual abstinence must be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, postovulation methods) and withdrawal are not acceptable methods of 
contraception. 
For subjects who practice true abstinence, subjects must be abstinent for at least 6 months prior 
to Screening and must agree to remain abstinent from the time of signing the ICF until 60 days 
after the EOS visit. 
If a subject who practices true abstinence at the time of signing the ICF becomes engaged in a 
heterosexual relationship, they must agree to use contraception as described previously from the 
time of signing the ICF until 60 days after the EOS visit. 
Same-sex Relationships 
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. 
If a subject who is in a same-sex relationship at the time of signing the ICF becomes engaged in 
a heterosexual relationship, they must agree to use contraception as described previously from 
the time of signing the ICF until 60 days after EOS.  

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Appendix 4: Collection of Pregnancy and Lactation Information 
Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking investigational product through 60 days after the last dose of 
investigational product. 
 Information will be recorded on the Pregnancy Notification Form (see Figure 6). The 
form must be submitted to Amgen Global Patient Safety within 24 hours of learning of a 
subject’s pregnancy. (Note: Sites are not required to provide any information on the 
Pregnancy Notification Form that violates the country or regions local privacy laws.) 
 After obtaining the female subject’s signed consent for release of pregnancy and infant 
health information, the Investigator will collect pregnancy and infant health information 
and complete the pregnancy questionnaire for any female subject who becomes pregnant 
while taking protocol-required therapies through 60 days after dosing of investigational 
product. This information will be forwarded to Amgen Global Patient Safety. Generally, 
infant Follow-up will be conducted up to 12 months after the birth of the child (if 
applicable). 
 Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for procedure.  
 While pregnancy itself is not considered to be an adverse event or serious adverse event, 
any pregnancy complication or elective termination of a pregnancy for medical reasons 
will be reported as an adverse event or serious adverse event. Abnormal pregnancy 
outcomes (e.g., spontaneous abortions, stillbirth, fetal death, congenital anomalies) will 
be reported as an adverse event or serious adverse event. Note that an elective 
termination with no information on a fetal congenital malformation or maternal 
complication is generally not considered an adverse event, but still must be reported to 
Amgen as a pregnancy exposure case. 
 Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the study treatment by the Investigator will be reported 
to Amgen Global Patient Safety as described in Appendix 1. While the Investigator is not 
obligated to actively seek this information in former study subjects, he or she may learn 
of a serious adverse event through spontaneous reporting.  
 Any female subject who becomes pregnant while participating will discontinue study 
treatment (see Section 4.7 for details). 
 
Male Subjects with Partners Who Become Pregnant or Were Pregnant at the Time of Enrollment 
 In the event a male subject fathers a child during treatment, and for an additional 60 days 
after dosing of investigational product. The information will be recorded on the 
Pregnancy Notification Form. The form (see Figure 6) must be submitted to Amgen 

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Global Patient Safety immediately and no later than 24 hours of the site’s awareness of 
the pregnancy. (Note: Sites are not required to provide any information on the Pregnancy 
Notification Form that violates the country or regions local privacy laws.) 
 Males whose partners become pregnant during treatment and for an additional 60 days 
after dosing of investigational product must practice sexual abstinence or use a condom 
through 60 days after dosing of investigational product and will be followed for safety 
until the end of study visit. 
 The Investigator will attempt to obtain a signed consent for release of pregnancy and 
infant health information directly from the pregnant female partner to obtain additional 
pregnancy information. 
 After obtaining the female partner’s signed consent for release of pregnancy and infant 
health information, the Investigator will collect pregnancy outcome and infant health 
information on the pregnant partner and her baby and complete the pregnancy 
questionnaires. This information will be forwarded to Amgen Global Patient Safety. 
 Generally, infant follow-up will be conducted up to 12 months after the birth of the child 
(if applicable).  
 Any termination of the pregnancy will be reported to Amgen Global Patient Safety 
regardless of fetal status (presence or absence of anomalies) or indication for procedure. 
Collection of Lactation Information 
 Investigator will collect lactation information on any female subject who breastfeeds 
while taking investigational product through 60 days after dosing of investigational 
product. 
 Information will be recorded on the Lactation Notification Form (Figure 7) and submitted 
to Amgen Global Patient Safety within 24 hours of the Investigator’s knowledge of event. 
 Study treatment will be discontinued if the female subject breastfeeds during the study. 
 With the female subject’s signed consent for release of mother and infant health 
information, the Investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while taking 
investigational product through 60 days after the last dose of investigational product.
With the female subject’s signed consent for release of mother and infant health information, the 
Investigator will collect mother and infant health information and complete the lactation 
questionnaire on any female subject who breastfeeds while taking protocol-required therapies 
through 60 days after discontinuing protocol-required therapies.

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Figure 6:  
Pregnancy Notification Form 
  

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Figure 7:  
Lactation Notification Form 
 
 

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Appendix 5: Sample Storage and Destruction 
When permitted by local regulations, any blood sample collected according to the Schedule of 
Assessments (Appendix 9) can be analyzed for any of the tests outlined in the protocol and for 
any tests necessary to minimize risks to study subjects. This includes testing to ensure analytical 
methods produce reliable and valid data throughout the course of the study. This can also 
include, but is not limited to, investigation of unexpected results, incurred sample reanalysis, and 
analyses for method transfer and comparability.  
All samples and associated results will be coded before being shipped from the site for analysis 
or storage. Samples will be tracked using a unique identifier that is assigned to the samples for 
the study. Results are stored in a secure database to ensure confidentiality.  

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Appendix 6: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines. 
 Applicable International Conference on Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines. 
 Applicable laws and regulations. 
The protocol, protocol amendments, Informed Consent Form (ICF), Investigator Brochure, and 
other relevant documents (e.g., advertisements) must be submitted to an Institutional Review 
Board (IRB) by the Investigator and reviewed and approved by the IRB before the study is 
initiated.  
Any amendments to the protocol will require IRB and regulatory authority (as locally required) 
approval before implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study subjects.  
The Investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB. 
 Notifying the IRB of serious adverse events or other significant safety findings as 
required by IRB procedures. 
 Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local regulations. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 
Informed Consent 
An initial sample ICF will be provided for the Investigator (or designee) to prepare the informed 
consent document to be used at his or her site. Updates to the sample ICF are to be 
communicated formally in writing from the Study Manager to the Investigator. The written ICF 
is to be prepared in the language(s) of the potential study participant population. 

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The Investigator or their delegated representative will explain to the subject, or their legally 
authorized representative, the aims, methods, anticipated benefits, and potential hazards of the 
study before any protocol-specific screening procedures or any investigational product(s) is/are 
administered and answer all questions regarding the study.  
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative (defined as an individual or other body authorized under applicable law 
to consent, on behalf of a prospective subject, to the subject’s participation in the clinical study) 
will then be required to sign a statement of informed consent that meets the requirements of 
21 CFR 50, local regulations, ICH guidelines, and the IRB or study site.  
The medical record must include a statement that written informed consent was obtained before 
the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
The acquisition of informed consent and the subject’s agreement or refusal of their notification 
of the primary care physician is to be documented in the subject’s medical records, and the ICF 
is to be signed and personally dated by the subject or a legally acceptable representative and by 
the person who conducted the informed consent discussion. Subject withdrawal of consent or 
discontinuation from study treatment and/or procedures must also be documented in the subject’s 
medical records. 
Subjects must be re-consented to the most current version of the ICF during their participation in 
the study.  
The original signed ICF is to be retained in accordance with institutional policy, and a copy of 
the ICF must be provided to the subject or the subject’s legally authorized representative.  
If a potential subject is illiterate or visually impaired and does not have a legally acceptable 
representative, the Investigator must provide an impartial witness to read the ICF to the subject 
and must allow for questions. Thereafter, both the subject and the witness must sign the ICF to 
attest that informed consent was freely given and understood. (Refer to ICH GCP guideline, 
Section 4.8.9.) 
A subject who is rescreened is not required to sign another ICF if the rescreening occurs within 
21 days from the previous ICF signature date and the same version of the ICF is in use at the 
time of rescreening. 
Subject Data Protection 
The Investigator must ensure that the subject’s confidentiality is maintained for documents 
submitted to the Sponsor. 

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Subjects will be assigned a unique identifier by the Sponsor (or designee). Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.  
On the electronic Case Report Form (eCRF) demographics page, in addition to the unique 
subject identification number (Section 4.4), include the age at time of enrollment. 
For serious adverse events reported to the Sponsor (or designee), subjects are to be identified by 
their unique subject identification number (Section 4.4), (for faxed reports, in accordance with 
local laws and regulations), and age (in accordance with local laws and regulations). 
Documents that are not submitted to the Sponsor (e.g., signed ICFs) are to be kept in confidence 
by the Investigator, except as described below. 
In compliance with ICH GCP Guidelines, it is required that the Investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and the IRB direct 
access to review the subject’s original medical records for verification of study-related 
procedures and data. Direct access includes examining, analyzing, verifying, and reproducing 
any records and reports that are important to the evaluation of the study.  
The Investigator is obligated to inform and obtain the consent of the subject to permit such 
individuals to have access to their study-related records, including personal information. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential information of the 
Sponsor, Amgen Inc. The Investigator (or designee) agrees not to disclose such information in 
any way without prior written permission from the Sponsor. The information in this document 
cannot be used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written permission from the Sponsor. 
The Investigator must ensure that the subject’s confidentiality is maintained for documents 
submitted to Amgen. 
Subjects will be assigned a unique identifier by the Sponsor (or designee). Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.  
On the Case Report Form demographics page, in addition to the unique subject identification 
number (Section 4.4), include the age at the time of enrollment. 
For serious adverse events reported to Amgen, subjects are to be identified by their unique 
subject identification number (Section 4.4), initials (for faxed reports, in accordance with local 
laws and regulations), and age (in accordance with local laws and regulations). 

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Documents that are not submitted to Amgen (e.g., signed ICFs) are to be kept in confidence by 
the Investigator, except as described below. 
Data Quality Assurance 
The following data quality steps will be implemented: 
 All relevant subject data relating to the study will be recorded on eCRFs unless directly 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.  
 The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
 The Investigator must permit study-related monitoring, audits, IRB review, and 
regulatory agency inspections and provide direct access to source data documents.  
 The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. Predefined agreed risks, monitoring thresholds, quality 
tolerance thresholds, controls, and mitigation plans will be documented in a risk 
management register. Additional details of quality checking to be performed on the data 
may be included in a Data Management Plan.  
 A Study Monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
 Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator in accordance with 21 CFR 312.62(c) unless local 
regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor.  
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 CFR Part 11-compliant 
electronic data capture system on an eCRF in a timely fashion. 
All data generated from external sources (e.g., laboratory and bioanalytical data), and transmitted 
to the Sponsor or designee electronically, will be integrated with the subject’s eCRF data in 
accordance with the Data Management Plan. 

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An eCRF must be completed for each enrolled subject who undergoes any screening procedures, 
according to the eCRF completion instructions. The Sponsor, or Contract Research Organization 
(Fortrea), will review the supporting source documentation against the data entered into the 
eCRFs to verify the accuracy of the electronic data. The Investigator will ensure that corrections 
are made to the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The Investigator will sign and date the eCRF via the electronic data capture system’s electronic 
signature procedure. These signatures will indicate that the Investigator reviewed and approved 
the data on the eCRF, data queries, and site notifications. 
Publications 
The policy for publication of data obtained during this study will be documented in the Clinical 
Study Agreement. 

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Appendix 7: Hepatotoxicity: Suggested Actions and Follow-up Assessments (Group 1 only) 
Subjects with normal hepatic function at Screening who experience aspartate aminotransferase 
(AST) or alanine aminotransferase (ALT) elevations  3 x upper limit of normal (ULN) or 
subjects with elevated values before drug exposure who have a 2-fold increase above baseline 
values (as specified in the Guidance for Industry Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation, July 2009) are to undergo clinical assessments and a period of “close 
observation” until abnormalities return to normal or to the subject’s baseline level as described 
below. 
 
Clinical Assessments and Observation 
Assessments that are to be performed during this period include:  
 Repeat AST, ALT, alkaline phosphatase, bilirubin (total and direct), and international 
normalized ratio (INR) within 24 hours as possible. 
 In cases of total bilirubin (TBL)  2 x ULN or INR  1.5, retesting of liver tests, bilirubin 
(total and direct), and INR is to be performed every 24 hours as possible until laboratory 
abnormalities improve. 
Testing frequency of the above laboratory tests may decrease if the abnormalities stabilize.  
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL. The 
following are to be considered depending on the clinical situation: 
 Complete blood count with differential to assess for eosinophilia 
 Serum total immunoglobulin G, anti-nuclear antibody anti-smooth muscle antibody, and 
liver kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 Serum acetaminophen (paracetamol) levels 
 A more detailed history of:  
o Prior and/or concurrent diseases or illness 
o Exposure to environmental and/or industrial chemical agents  
o Symptoms (if applicable) including right upper quadrant pain, 
hypersensitivity-type reactions, fatigue, nausea, vomiting, and fever 
o Prior and/or concurrent use of alcohol, recreational drugs, and special diets 
o Concomitant use of medications (including nonprescription medicines and herbal 
and dietary supplements), plants, and mushrooms 
 Viral serologies 
 Creatine phosphokinase, haptoglobin, lactate dehydrogenase, and peripheral blood smear 
 Appropriate liver imaging if clinically indicated 

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 Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected 
 Hepatology consult (liver biopsy may be considered in consultation with a hepatologist). 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or are considered stable by the Investigator. The 
“close observation period” is to continue for a minimum of 4 weeks after discontinuation of all 
investigational product(s) and protocol-required therapies. 
The potential drug-induced liver injury (DILI) event and additional information such as medical 
history, concomitant medications, and laboratory results must be captured in the corresponding 
electronic Case Report Form (eCRF). 
Important alternative causes for elevated AST/ALT and/or TBL values include, but are not 
limited to: 
 Hepatobiliary tract disease 
 Viral hepatitis (e.g., hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 Right-sided heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
 Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms 
 Heritable disorders causing impaired glucuronidation (e.g., Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (e.g., indinavir, 
atazanavir) 
 Alpha-one antitrypsin deficiency 
 Alcoholic hepatitis 
 Autoimmune hepatitis 
 Wilson’s disease and hemochromatosis 
 Nonalcoholic fatty liver disease including steatohepatitis 
 Non-hepatic causes (e.g., rhabdomylosis, hemolysis). 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, i.e., cases of AST or ALT  3 x ULN 
and concurrent TBL  2 x ULN or INR  1.5 (for subjects not on anticoagulation therapy) 
without evidence of alternative cause of the elevations, require the following: 

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 The event is to be reported to the Sponsor as a serious adverse event within 24 hours of 
discovery or notification of the event (i.e., before additional etiologic investigations have 
been concluded) 
 The appropriate eCRF captures information necessary to facilitate the evaluation of 
treatment-emergent liver abnormalities is to be completed and sent to the Sponsor. 
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse events if 
they meet the criteria for a serious adverse event defined in Appendix 1. 

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Appendix 8: Hepatotoxicity Stopping Rules: Suggested Actions and Follow-up Assessments 
(Group 2 only) 
Subjects with abnormal hepatic laboratory values (i.e., alkaline phosphatase [ALP], aspartate 
aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) and/or 
international normalized ratio (INR) and/or signs/symptoms of hepatitis (as described below) 
may meet the criteria for withholding or permanent discontinuation of Amgen investigational 
product or other protocol-required therapies, as specified in the Guidance for Industry 
Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009. 
Criteria for Withholding and/or Permanent Discontinuation of Amgen Investigational 
Product and Other Protocol-required Therapies Due to Potential Hepatotoxicity 
The following stopping and/or withholding rules apply to subjects for whom another cause of 
their changes in liver biomarkers (TBL, INR, and transaminases) has not been identified.  
Important alternative causes for elevated AST/ALT and/or TBL values include, but are not 
limited to: 
 Hepatobiliary tract disease 
 Viral hepatitis (e.g., hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 Right-sided heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
 Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms 
 Heritable disorders causing impaired glucuronidation (e.g., Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (e.g., indinavir, 
atazanavir) 
 Alpha-one antitrypsin deficiency 
 Alcoholic hepatitis 
 Autoimmune hepatitis 
 Wilson’s disease and hemochromatosis 
 Nonalcoholic fatty liver disease including steatohepatitis 
 Non-hepatic causes (e.g., rhabdomylosis, hemolysis). 
If investigational product(s) is/are withheld, the subject is to be followed for possible 
drug-induced liver injury (DILI) according to recommendations in the last section of this 
appendix.  

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Rechallenge may be considered if an alternative cause for impaired liver tests (ALT, AST, ALP) 
and/or elevated TBL is discovered and the laboratory abnormalities resolve to normal or baseline 
(see next section in this appendix). 
Table 3: 
Conditions for Permanent Discontinuation of Amgen Investigational Product 
and Other Protocol-required Therapies Due to Potential Hepatotoxicity 
Analyte 
Temporary Withholding  
TBL 
3x ULN at any time 
INR 
-- 
 
OR 
AST/ALT 
8x ULN at any time 
5x ULN but 8x ULN for 2 weeks 
5x ULN but 8x ULN and unable to adhere to enhanced 
monitoring schedule 
3x ULN with clinical signs or symptoms that are consistent with 
hepatitis (such as right upper quadrant pain/tenderness, fever, 
nausea, vomiting, and jaundice) 
OR 
ALP 
8x ULN at any time 
Abbreviations: ALP  alkaline phosphatase; ALT  alanine aminotransferase; AST  aspartate aminotransferase; 
INR  international normalized ratio; TBL  total bilirubin; ULN  upper limit of normal. 
 

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Table 4: 
Conditions for Withholding Amgen Investigational Product and Other 
Protocol-required Therapies Due to Potential Hepatotoxicity 
Analyte 
Permanent Discontinuation  
TBL 
2x ULN 
OR 
INR 
1.5 (for subjects not on anticoagulation therapy) 
AND 
AST/ALT 
3x ULN (when baseline was  ULN), in the presence of no 
important alternative causes for elevated AST/ALT and/or TBL 
values 
 
ALP 
-- 
Abbreviations: ALP  alkaline phosphatase; ALT  alanine aminotransferase; AST  aspartate aminotransferase; 
INR  international normalized ratio; TBL  total bilirubin; ULN  upper limit of normal. 
 
Criteria for Rechallenge of Amgen Investigational Product and Other Protocol-required 
Therapies After Potential Hepatotoxicity 
The decision to rechallenge the subject is to be discussed and agreed upon unanimously by the 
subject, Investigator, and Amgen. 
If signs or symptoms recur with rechallenge, then avacopan is to be permanently discontinued. 
Subjects who clearly meet the criteria for permanent discontinuation (as described in Table 3) are 
never to be rechallenged. 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT and 
TBL and/or INR elevation, according to the criteria specified above, require the following: 
 The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (i.e., before additional etiologic investigations 
have been concluded). 
 The appropriate electronic Case Report Form (eCRF) that captures information 
necessary to facilitate the evaluation of treatment-emergent liver abnormalities is to 
be completed and sent to Amgen. 

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Other events of hepatotoxicity and potential DILI are to be reported as serious adverse events if 
they meet the criteria for a serious adverse event defined in Appendix 1. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are withheld 
(either permanently or conditionally) due to potential DILI as specified in Table 3 and Table 4 or 
who experience AST or ALT elevations 3 x upper limit of normal (ULN) or 2-fold increases 
above baseline values for subjects with elevated values before drug are to undergo a period of 
“close observation” until abnormalities return to normal or to the subject’s baseline levels.  
Assessments that are to be performed during this period include:  
 Repeat AST, ALT, ALP, bilirubin (total and direct), and INR within 24 hours as 
possible 
 In cases of TBL 2x ULN or INR  1.5, retesting of liver tests, BIL (total and direct) 
and INR is to be performed every 24 hours as possible until laboratory abnormalities 
improve. 
Testing frequency of the above laboratory tests may decrease if the abnormalities stabilize or the 
investigational product(s) or protocol-required therapies has/have been discontinued AND the 
subject is asymptomatic. 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL.  
The following are to be considered depending on the clinical situation: 
 Complete blood count with differential to assess for eosinophilia 
 Serum total immunoglobulin G, anti-nuclear antibody anti-smooth muscle antibody, and liver 
kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 Serum acetaminophen (paracetamol) levels 
 A more detailed history of: 
o Prior and/or concurrent disease or illness 
o Exposure to environmental and/or industrial chemical agents 
o Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-
type reactions, fatigue, nausea, vomiting and fever 
o Prior and/or concurrent use of alcohol, recreational drugs, and special diets 
o Concomitant use of medications (including nonprescription medicines and herbal 
and dietary supplements), plants, and mushrooms 
 Viral serologies 

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 Creatine phosphokinase, haptoglobin, lactate dehydrogenase, and peripheral blood smear 
 Appropriate liver imaging if clinically indicated 
 Appropriate blood sampling for pharmacokinetic analysis, if this has not already been 
collected 
 Hepatology consult (liver biopsy may be considered in consultation with a hepatologist). 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the Investigator. The “close 
observation period” is to continue for a minimum of 4 weeks after discontinuation of all 
investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications, and laboratory results must be captured in the corresponding eCRFs.  
 

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Appendix 9: Schedule of Assessments 

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f 12-lead ECGs will be collected after the subject has rested in the supine position for at least 5 minutes, and will be obtained prior to the scheduled blood draws at: Check-in; 
Day 8; and Day 18 (EOS or ET). Electrocardiograms should be collected prior to any PK corresponding timepoints. Single trace ECGs will be collected at all timepoints. 
g Vital signs measurements (seated/supine blood pressure, seated/supine pulse rate, respiratory rate, and oral body temperature) should be carried out prior to having blood drawn. 
Vital signs will be obtained at: Check-in; prior to avacopan administration and 4 hours following avacopan administration on Day 1, 24 hours postdose on Day 2, and on Days 3, 
4, 5, 6, 7, 8, and 18 (EOS or ET). Pulse rate and blood pressure will be measured using the same arm for each reading after the subject has been resting in the seated/supine 
position for at least 5 minutes. 
h Clinical chemistry and hematology (fasted at least 8 hours). Urinalysis will not be performed for subjects in Group 2. 
i The eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation. 
  MDRD formula (mL/min/1.73m2)  175 x(serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.212 if African American) 
j Hemodialysis will be completed on Day -1 before the administration of avacopan. Hemodialysis will occur on Days 3, 5, and 7. Hemodialysis will continue as needed beyond the 
timepoints specified in the SOA. The study day, and the start and end times will be collected for all HD sessions. 
k The PK samples collected on Day 1 will have a sampling window of 10 minutes. Postdose samples on Day 2 will have a sampling window of 1 hour. Postdose samples Days 3 
to 8 will have a sampling window of 2 hours. Postdose samples on Days 12, 15, and 18 will have a sampling window of 4 hours. Times of all PK samples will be recorded to 
the nearest minute. Day 3, Day 5, and Day 7 PK samples will be obtained prior to start of HD. 
l Dose administration of avacopan will be given in the morning on Day 1 under fed conditions following HD session on Day -1.

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Appendix 10: Child-Pugh Classification of Severity of Cirrhosis 
Parameter 
Points Assigned 
1 
2 
3 
Ascites1 
Absent 
Slight or Subject on 1 
medication to control 
ascites 
Moderate or Severe 
or Subject on 2 
medications to 
control ascites 
Total bilirubin 
 2 mg/dL 
( 34.2 mol/L) 
2 – 3 mg/dL 
(34.2 – 51.3 mol/L) 
 3 mg/dL 
( 51.3 mol/L) 
Albumin 
 3.5 g/dL 
(35 g/L) 
2.8 – 3.5 g/dL 
(28 – 35 g/L) 
 2.8 g/dL 
( 28 g/L) 
Prothrombin time 
 
 
 
Seconds over control 
 4 
4 – 6  
 6 
International normalized ratio 
 1.7 
1.7 – 2.3 
 2.3 
Hepatic encephalopathy2 
None 
Grade 1 – 2  
(or suppressed with 
medication) 
Grade 3 – 4 
(refractory) 
1  Ascites is graded according to the following criteria: 
Absent: No ascites detectable by manual investigation 
Slight: Ascites palpitation doubtful 
Moderate: Ascites detectable by palpation 
Severe: Necessity of paracentesis, does not respond to medication treatment. 
2  Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles per second waves 
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2 to 3 cycles per second delta activity 
 
Modified Child-Pugh classification of the severity of liver disease according to the degree of 
ascites, the serum concentrations of total bilirubin and albumin, the prothrombin time (or 
international normalized ratio), and the degree of hepatic encephalopathy. A total score of 5 to 6 
is considered Class A (well compensated disease); 7 to 9 is Class B (significant functional 
compromise); and 10 to 15 is Class C (decompensated disease).  
 
Subjects in Group 1 will not be assessed for Child-Pugh Scores. Subjects in Group 2 with a 
Class  C Child-Pugh classification will be excluded from the study. Child-Pugh will only be 
evaluated for subjects deemed to have active liver disease by the Investigator (or designee). 

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Protocol 
A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, 
Safety, and Tolerability of Avacopan in Subjects with Normal Renal Function 
and Subjects with End-Stage Renal Disease (ESRD) Requiring Hemodialysis 
Protocol Status: Final 
Protocol Date: 26 April 2024 
Original Protocol 
Investigational Product: Avacopan 
Amgen Protocol Reference Number: 20230265 
Fortrea Study Number: 8530204 
  
 
 
Sponsor: 
Amgen, Inc. 
One Amgen Center Drive 
Thousand Oaks, California 91320 
 
 
This protocol was developed, reviewed, and approved in accordance with Fortrea’s 
standard operating procedures. This format and content of this protocol is aligned with 
Good Clinical Practice: Consolidated Guidance (ICH E6). 
 

Protocol 
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Confidentiality Notice 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staffs and 
members of the Institutional Review Board/Independent Ethics Committee/Institutional 
Scientific Review Board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number: US sites, 1- 800-77-AMGEN; Amgen’s general 
number in the US, 1-805-447-1000. 

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INVESTIGATOR AGREEMENT 
I have read the attached protocol entitled “A Phase 1, Open-label, Single-dose Study to Evaluate 
the Pharmacokinetics, Safety, and Tolerability of Avacopan in Subjects with Normal Renal 
Function and Subjects with End-Stage Renal Disease (ESRD) Requiring Hemodialysis” dated 
26 April 2024 and agree to abide by all provisions set forth therein. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite Guideline 
on Good Clinical Practice (GCP), Declaration of Helsinki, and applicable national or regional 
regulations/guidelines.  
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of Amgen Inc. 
I agree not to share the confidential information contained in this document without the prior 
written consent of Amgen Inc. 
 
_______________________________ 
Signature 
 
_______________________________ 
____________________________ 
Name of Investigator  
Date (DD Month YYYY) 
 
_______________________________ 
Title and Role of Investigator 
 
_______________________________ 
Institution Name 
 
_______________________________ 

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Address and Telephone Number of Institution 
 
_______________________________________ 
 
 
 
 
 
                                  

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SYNOPSIS 
Title of study: A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, 
Safety, and Tolerability of Avacopan in Subjects with Normal Renal Function and Subjects 
with End-Stage Renal Disease (ESRD) Requiring Hemodialysis 
Objectives:  
The primary objective of the study is: 
 
to evaluate the pharmacokinetics (PK) of avacopan and metabolite (M1) after a single 
dose of avacopan in subjects with normal renal function and subjects with ESRD 
requiring hemodialysis (HD). 
The secondary objective of the study is: 
 
to evaluate the safety and tolerability of a single dose of avacopan in subjects with 
normal renal function and subjects with ESRD requiring HD. 
Study design: 
This will be a Phase 1, open label, single-dose, parallel group study to evaluate the PK, safety, 
and tolerability of avacopan in subjects with normal renal function (Group 1) and subjects with 
ESRD requiring HD (Group 2). After informed consent is obtained, potential subjects will be 
screened to assess their eligibility to enter the study within 28 days prior to the first dose 
administration. 
Subjects in Group 1 (normal renal function) will be admitted into the Clinical Research Unit 
(CRU) on Day -1 and will be confined to the CRU until discharge on Day 8.  
Subjects in Group 1 will receive a single 
 dose of avacopan on Day 1 under fed 
conditions. Following discharge on Day 8, subjects will return to the CRU on Days 12, 15, and 
18 (end of study [EOS] visit) for outpatient visits.  
Subjects in Group 2 (ESRD requiring HD) will receive a single dose of 
 avacopan under 
fed conditions on Day 1 in each of the 2 treatment periods (Period 1/on HD and Period 2/off 
HD). Subjects in Group 2 will be admitted into the CRU on Period 1 Day -1. Subjects in Group 
2 Period 1 (on HD) will receive a single 
 dose of avacopan on Period 1 Day 1, 4 hours 
prior to the start of HD. Subjects will continue to receive HD on Days 3, 5, and 8 (prior to 
discharge). Following discharge on Day 8, subjects will return to the CRU on Period 1 Days 
12, 15, and 18 for outpatient visits. Subjects in Group 2 will be re-admitted into the CRU for 
Period 2 Day -1 on the day of their HD. Period 1 Day 18 may occur on the same day as Period 
2 Day -1. Subjects will receive a single 
 dose of avacopan on Period 2 Day 1 on an off-
HD day (one day after the HD session on Period 2 Day -1). Subjects will continue to receive 
HD on Days 3, 5, and 7. Subjects will be confined to the CRU until discharge on Period 2 Day 
8. Following discharge on Period 2 Day 8, subjects in Group 2 will return to the CRU on 
Period 2 Days 12, 15, and 18 (EOS) for outpatient visits. There will be no washout between 
Day 18 of Period 1 and Check-in for Period 2 for subjects in Group 2.  
Number of subjects: 
Approximately 12 subjects will be enrolled in 2 groups (Groups 1 and 2). Approximately 
6 subjects will be enrolled in each group. 
Diagnosis and main criteria for inclusion: 
Male subjects or female subjects, 18 to 75 years of age (inclusive), and body mass index of 18 
to 40 kg/m2 with normal renal function or ESRD requiring HD. 
Investigational products, dose, and mode of administration: 
Investigational Medicinal Product: 
 avacopan oral dose under fed conditions 
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Duration of subject participation in the study: 
Planned Screening duration: 4 weeks. 
Planned study duration (Screening to EOS): Group 1: approximately 7 weeks,  
Group 2: approximately 9 weeks.  
Primary Endpoints: 
The primary endpoints for this study are avacopan and M1 PK parameters: maximum observed 
plasma concentration (Cmax); area under the plasma concentration-time curve (AUC) from time 
zero to time of last quantifiable concentration (AUClast); area under the plasma 
concentration-time curve from time zero to infinity (AUCinf); area under the plasma 
concentration time curve from time zero to 48 hours (AUC0-48), or other partial area 
comparisons, as appropriate; and HD clearance of drug (and metabolite) from plasma (CLD). 
Secondary Endpoints: 
Secondary endpoints for this study are: treatment-emergent adverse events and serious adverse 
events. 
Statistical methods: 
The primary PK parameters are Cmax and AUC. All other PK parameters will be regarded as 
secondary and will not be subject to inferential statistical analysis. To determine the effect of 
renal impairment on the PK of avacopan and M1, the ratios (test/reference) for the model-
estimated Cmax, AUClast, and AUCinf for the ESRD group (test) relative to the group with 
normal renal function (reference) will be generated, along with 90 confidence intervals. 
Applicable PK parameters in the ESRD group on-HD days and off-HD days may also be 
compared. 
 
The final safety analysis for the study will be performed at EOS. Adverse events will be 
summarized using descriptive methodology. Each adverse event will be coded using the 
Medical Dictionary for Regulatory Activities. Endpoints for clinical laboratory tests, 
electrocardiogram, and vital signs will be summarized. 
 
Additional details will be included in the Statistical Analysis Plan. 

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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................5 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS ...........................................................................................................8 
LIST OF TABLES AND FIGURES........................................................................................11 
LIST OF ABBREVIATIONS ..................................................................................................12 
1. 
INTRODUCTION ...........................................................................................................14 
1.1. 
Background ............................................................................................................14 
1.2. 
Pharmacokinetics ...................................................................................................14 
1.3. 
Study Rationale ......................................................................................................15 
1.4. 
Benefit-risk Assessment.........................................................................................15 
1.4.1. 
Therapeutic Context .....................................................................................15 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................16 
2.1. 
Objectives ..............................................................................................................16 
2.2. 
Endpoints ...............................................................................................................17 
2.2.1. 
Primary Endpoints .......................................................................................17 
2.2.2. 
Secondary Endpoints ...................................................................................17 
3. 
INVESTIGATIONAL PLAN ..........................................................................................17 
3.1. 
Overall Study Design and Plan ..............................................................................17 
3.2. 
Discussion of Study Design ...................................................................................22 
3.3. 
Selection of Doses in the Study .............................................................................22 
4. 
SELECTION OF STUDY POPULATION .....................................................................22 
4.1. 
Inclusion Criteria ...................................................................................................22 
4.2. 
Exclusion Criteria ..................................................................................................23 
4.3. 
Screen Failures and Rescreening ...........................................................................27 
4.4. 
 ........................................................................28 
4.5. 
Subject Withdrawal and Replacement ...................................................................28 
4.6. 
Study Termination .................................................................................................28 
4.7. 
Discontinuation of Study Treatment (Group 2 only) .............................................29 
5. 
STUDY TREATMENTS .................................................................................................30 
5.1. 
Investigational Product ..........................................................................................30 
5.2. 
Investigational Product Administration .................................................................31 
5.3. 
Treatment of Overdose ..........................................................................................31 
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5.3.1. 
Medical Devices...........................................................................................31 
5.3.2. 
Product Complaints ......................................................................................31 
5.4. 
Randomization .......................................................................................................31 
5.5. 
Blinding..................................................................................................................32 
5.6. 
Treatment Compliance ...........................................................................................32 
5.7. 
Drug Accountability...............................................................................................32 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................32 
6.1. 
Concomitant Therapies ..........................................................................................32 
6.2. 
Diet .........................................................................................................................33 
6.3. 
Smoking .................................................................................................................33 
6.4. 
Exercise ..................................................................................................................34 
6.5. 
Blood Donation ......................................................................................................34 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................34 
7.1. 
Pharmacokinetic Assessments ...............................................................................34 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................34 
7.1.2. 
Analytical Methodology ..............................................................................35 
7.2. 
Safety and Tolerability Assessments .....................................................................35 
7.2.1. 
Adverse Events and Serious Adverse Events: Time period and Frequency 
for Collecting and Reporting Safety Event Information ..............................35 
7.2.2. 
Clinical Laboratory Evaluations ..................................................................39 
7.2.3. 
Vital Signs ....................................................................................................39 
7.2.4. 
12-lead Electrocardiogram ...........................................................................40 
7.2.5. 
Physical Examination...................................................................................40 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................40 
8.1. 
Determination of Sample Size ...............................................................................40 
8.2. 
Analysis Populations ..............................................................................................41 
8.2.1. 
Pharmacokinetic Population ........................................................................41 
8.2.2. 
Safety Population .........................................................................................41 
8.3. 
Pharmacokinetic Analyses .....................................................................................41 
8.4. 
Safety Analysis ......................................................................................................42 
8.5. 
Interim Analysis .....................................................................................................42 
9. 
REFERENCES ................................................................................................................42 
10. APPENDICES .................................................................................................................43 
Appendix 1: Safety Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting of Adverse Events and Serious Adverse Events ..........44 
Definition of Adverse Event ........................................................................................44 

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Definition of Serious Adverse Event ...........................................................................45 
Recording Adverse Events and Serious Adverse Events .............................................47 
Evaluating Adverse Events and Serious Adverse Events ............................................49 
Reporting of Serious Adverse Event............................................................................50 
Appendix 2: Clinical Laboratory Evaluations ...................................................................54 
Appendix 3: Contraception Requirements .........................................................................55 
Appendix 4: Collection of Pregnancy and Lactation Information .....................................58 
Appendix 5: Sample Storage and Destruction ...................................................................62 
Appendix 6: Regulatory, Ethical, and Study Oversight Considerations ............................63 
Appendix 7: Hepatotoxicity: Suggested Actions and Follow-up Assessments (Group 1 
only) .......................................................................................................................68 
Appendix 8: Hepatotoxicity Stopping Rules: Suggested Actions and Follow-up 
Assessments (Group 2 only) ..................................................................................71 
Appendix 9: Schedule of Assessments ..............................................................................76 
 

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LIST OF TABLES AND FIGURES 
Table 1: 
Classification of Renal Function Study Groups.........................................19 
Table 2: 
Investigational Product ..............................................................................30 
Table 3: 
Conditions for Permanent Discontinuation of Amgen Investigational 
Product and Other Protocol-required Therapies Due to Potential Hepatotoxicity .......72 
Table 4: 
Conditions for Withholding Amgen Investigational Product and Other 
Protocol-required Therapies Due to Potential Hepatotoxicity .....................................73 
  
Figure 1:  
Study Schema – Group 1 (Normal Renal Function) ..................................19 
Figure 2:  
Study Schema – Group 2 (ESRD Requiring Hemodialysis) .....................20 
Figure 3: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 1 – On 
Hemodialysis ................................................................................................................21 
Figure 4: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 2 – Off 
Hemodialysis ................................................................................................................21 
Figure 5:  
Sample Serious Adverse Event Report Form ............................................51 
Figure 6:  
Pregnancy Notification Form .....................................................................60 
Figure 7:  
Lactation Notification Form ......................................................................61 
 

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LIST OF ABBREVIATIONS 
Abbreviation Definition 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCA 
anti-neutrophil cytoplasmic autoantibody 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
AUCinf 
area under the plasma concentration-time curve from time zero to 
infinity 
AUClast 
area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration 
AUC0-48 
area under the plasma concentration-time curve from time zero to 
48 hours postdose 
BIL 
bilirubin 
BP 
blood pressure 
C5a 
complement component C5a 
C5aR 
complement 5a receptor 
CFR 
Code of Federal Regulations 
CLD 
hemodialysis clearance of drug (and metabolite) from plasma 
Cmax 
maximum observed plasma concentration 
CRF 
Case Report Form 
CRF 
Case Report Form 
CRU 
Clinical Research Unit 
CTCAE 
Common Terminology Criteria for Adverse Events  
CV 
coefficient of variation 
CYP3A4 
cytochrome P450 3A4 
DILI 
drug-induced liver injury 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
ESRD 
end-stage renal disease 
FSH 
follicle-stimulating hormone 

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fu 
fraction of unbound drug; reported as the arithmetic mean where 
measured at two time points 
GCP 
Good Clinical Practice 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HD 
hemodialysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
MDRD 
Modification of Diet in Renal Disease 
OSF 
Other Safety Finding 
PK 
pharmacokinetic(s) 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
SS 
Special Situation 
TBL 
total bilirubin 
tmax 
time of the maximum observed concentration 
ULN 
upper limit of normal 

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1. INTRODUCTION 
Refer to the Investigator’s Brochure (IB)1, Prescribing Information2, and Summary of Product 
Characteristics3 for detailed information concerning the available pharmacology, toxicology, 
drug metabolism, clinical studies, and adverse event profile of the investigational medicinal 
product (IMP). 
1.1. 
Background 
Investigational Medicinal Product 
In the United States, TAVNEOS (formerly CCX168), hereafter referred to as avacopan, is 
currently approved as an adjunctive treatment of adult patients with severe active anti-neutrophil 
cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis and 
microscopic polyangiitis) in combination with standard therapy including glucocorticoids. 
Avacopan does not eliminate glucocorticoid use. Avacopan is also approved in the European 
Union for use in combination with a rituximab or cyclophosphamide regimen and is indicated for 
the treatment of adult patients with severe, active granulomatosis with polyangiitis or 
microscopic polyangiitis. Avacopan has also been approved in Canada, Great Britain, 
Switzerland, Japan, and the United Arab Emirates, and is under review in several other countries 
for marketing authorization.  
Avacopan is a highly potent and selective antagonist of the human complement 5a (C5a) receptor 
(C5aR), acting through competitive inhibition of the interaction between human C5aR and the 
anaphylatoxin complement component C5a; the latter is produced through activation of the 
complement cascade. As a result of its mechanism of action, avacopan reduces neutrophil 
activation, chemoattraction, and integrin expression. Avacopan inhibits vascular endothelial cell 
retraction and permeability, ameliorating the necrotizing vasculitis associated with 
ANCA-associated vasculitis.  
A summary of completed clinical studies for avacopan is provided in the IB (Table 6).1 
1.2. 
Pharmacokinetics 
The pharmacokinetics (PK) of avacopan has been evaluated in nine Phase 1 studies, two Phase 2 
studies, and one Phase 3 study in patients with ANCA-associated vasculitis.  
Following single oral administration in healthy subjects at doses ranging from 1 to 100 mg, 
avacopan was absorbed rapidly with maximum observed plasma concentration (Cmax) occurring 
approximately 1 to 2.5 hours postdose. Avacopan is primarily eliminated via extensive 
metabolism mediated through cytochrome P450 3A4 (CYP3A4) oxidation in the liver which 
results in the formation of and clearance of the major circulating metabolite, M1, a 
mono-hydroxylated product of avacopan. Following metabolism, the metabolites are primarily 
excreted into feces via bile. In the Phase 1 food-effect study, following a single oral dose of 
30 mg in the presence of a high-fat, high-calorie meal, avacopan exposures, area under the 

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plasma concentration-time curve (AUC), and Cmax, increased by approximately 72 and 8, 
respectively, and delayed the time of the maximum observed concentration (tmax) by 
approximately 4 hours (from 2.0 hours to 6.0 hours). The elimination half-lives of avacopan and 
M1 were 97.6 hours and 55.6 hours, respectively, under fed conditions. Following oral 
administration of avacopan 100 mg/400 Ci, about 77 and 10 of the radioactive dose was 
recovered in feces and urine, respectively, and 7 and 0.1 of the radioactive dose was 
recovered as unchanged avacopan in feces and urine, respectively. Avacopan and metabolite M1 
are more than 99.9 plasma-protein bound, primarily to albumin and 1-acid glycoprotein. A 
Phase 1 study in subjects with hepatic impairment evaluated the PK of avacopan and metabolite 
M1 following a single 
 dose for up to 18 days. Results from this study showed that plasma 
avacopan levels appeared to decline with a triphasic profile with a rapid early phase, followed by 
a longer phase, and finally a terminal phase with a half-life of about 200 to 400 hours in most 
subjects. Metabolite M1 appeared to decline in a biphasic manner with an elimination half-life of 
about 68 to 73 hours.2 
Previously, the impact of moderate renal impairment (estimated glomerular filtration rate [eGFR] 
between 30 and less than 60 mL/min/1.73 m2) and severe renal impairment (less than 
30 mL/min/1.73 m2) from patients with ANCA-associated vasculitis from Phase 2 and Phase 3 
studies relative to subjects with normal renal function (eGFR 90 mL/min/1.73 m2) from Phase 1 
studies were evaluated using population PK analysis. Results from population PK analyses 
demonstrated that avacopan and M1 exposures as assessed by Cmax and AUC were similar 
(20) across the different categories. Therefore, no dose adjustment for avacopan is needed 
based on renal function.1 
1.3. 
Study Rationale 
This study will be conducted to evaluate the PK of a single dose of avacopan in subjects with 
normal renal function and in subjects with end-stage renal disease (ESRD) requiring 
hemodialysis (HD). 
Results from this study will provide information on the safety, tolerability, and PK of avacopan 
and potentially guide dosing in patients with ESRD requiring HD. 
1.4. 
Benefit-risk Assessment 
The following benefit-risk assessment supports the conduct of this clinical study. Refer to the IB1 
for more information. 
1.4.1. 
Therapeutic Context 
1.4.1.1. 
Key Benefits 
Healthy and ESRD subjects in the current study will not receive any health benefit (beyond that 
of an assessment of their medical status) from participating in the study.  
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The secondary objective of the study is: 
 to evaluate the safety and tolerability of a single dose of avacopan in subjects with 
normal renal function and subjects with ESRD requiring HD. 
2.2. 
Endpoints 
2.2.1. 
Primary Endpoints 
The primary endpoints of the study are: 
 Cmax 
 area under the plasma concentration-time curve from time zero to time of last 
quantifiable concentration (AUClast) 
 area under the plasma concentration-time curve from time zero to infinity (AUCinf) 
 area under the plasma concentration-time curve from time zero to 48 hours (AUC0-48), or 
other partial area comparisons, as appropriate 
 HD clearance of drug (and metabolite) from plasma (CLD). 
2.2.2. 
Secondary Endpoints 
The secondary endpoints of the study are: 
 treatment-emergent adverse events 
 serious adverse events. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase 1, open-label, single-dose, parallel group study to evaluate the PK, safety, 
and tolerability of avacopan in subjects with normal renal function (Group 1) and subjects with 
ESRD requiring HD (Group 2). After informed consent is obtained, potential subjects will be 
screened to assess their eligibility to enter the study within 28 days prior to the first dose 
administration. 
Subjects in Group 1 (normal renal function) will be admitted into the Clinical Research Unit 
(CRU) on Day -1 and will be confined to the CRU until discharge on Day 8. Subjects in Group 1 
will receive a single 
 dose of avacopan on Day 1 under fed conditions. Following 
discharge on Day 8, subjects will return to the CRU on Days 12, 15, and 18 (end of study [EOS] 
visit) for outpatient visits. An overview of the study schema for Group 1 is shown in Figure 1. 
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Subjects in Group 2 (ESRD requiring HD) will receive a single dose of 
 avacopan under 
fed conditions on Day 1 in each of the 2 treatment periods (Period 1/on HD and Period 2/off 
HD). An overview of the study schema for Group 2 is shown in Figure 2. 
Subjects in Group 2 will be admitted into the CRU on Period 1 Day -1 and will be confined to 
the CRU until discharge on Period 1 Day 8. Subjects in Group 2 Period 1 (on HD) will receive a 
single 
 dose of avacopan on Period 1 Day 1, 4 hours prior to the start of HD. Subjects will 
continue to receive HD on Days 3, 5, and 8 (prior to discharge). Following discharge on Day 8, 
subjects will return to the CRU on Period 1 Days 12, 15, and 18 for outpatient visits. The 
Group 2 Period 1 (on HD) schema is shown in Figure 3. 
Subjects in Group 2 will be re-admitted into the CRU for Period 2 Day -1 on the day of their HD. 
Period 1 Day 18 may occur on the same day as Period 2 Day -1. Subjects will receive a single 
 dose of avacopan on Period 2 Day 1 on an off-HD day (one day after the HD session on 
Period 2 Day -1). Subjects will continue to receive HD on Days 3, 5, and 7. Subjects will be 
confined to the CRU until discharge on Period 2 Day 8. Following discharge on Period 2 Day 8, 
subjects in Group 2 will return to the CRU on Period 2 Days 12, 15, and 18 (EOS) for outpatient 
visits. The Group 2 Period 2 (off-HD) schema is shown in Figure 4. There will be no washout 
between Day 18 of Period 1 and Check-in for Period 2 for subjects in Group 2. 
Additional plasma samples will be collected for estimation of plasma protein binding.  
The eGFR will be determined by the Modification of Diet in Renal Disease (MDRD) formula4: 
MDRD formula (mL/min/1.73m2)  175 x (serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) 
x (1.212 if African American) 
The renal function groups and eGFR values used to assign each subject to a renal function group 
are shown in Table 1. 
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Figure 3: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 1 – On 
Hemodialysis 
 
Abbreviations: HD  hemodialysis. 
Notes: Subjects will receive a single oral dose of avacopan 4 hours prior to start of HD session, under fed 
conditions. See Appendix 9 (Schedule of Assessments) for details on plasma pharmacokinetics, plasma protein 
binding sampling, and dialysate pharmacokinetics sampling. 
Figure 4: 
Group 2 (ESRD Requiring Hemodialysis) Schema, Period 2 – Off 
Hemodialysis 
 
Abbreviations: EOS  end of study; ET  early termination; HD  hemodialysis. 
Notes: Subjects will receive a single oral dose of avacopan 1 day after the HD session. See Appendix 9 (Schedule of 
Assessments) for details on plasma pharmacokinetics and plasma protein binding sampling. 

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The total duration of study participation for each subject (from Screening through EOS visit) is 
anticipated to be approximately 7 weeks for Group 1 (normal renal function) and approximately 
9 weeks for Group 2 (ESRD requiring HD). 
The start of the study is defined as the date the first enrolled subject signs an Informed Consent 
Form (ICF). The point of enrollment occurs at the time of subject number allocation. The end of 
the study is defined as the date of the last subject’s last assessment (scheduled or unscheduled).  
A Schedule of Assessments is presented in Appendix 9. 
3.2. 
Discussion of Study Design 
This study will be open label because the study endpoints are not considered subjective. 
The PK results from prior Phase 1 studies demonstrated relatively linear and dose-proportional 
PK, suggesting that a single-dose study in subjects with renal impairment should adequately 
describe the PK of the drug. The safety and PK assessments are standard parameters for clinical 
studies in drug development. 
Plasma sampling is timed to sufficiently estimate PK parameters of avacopan exposure, based on 
characteristics of the concentration-time profile. 
This study will be conducted in subjects with normal renal function and in subjects with stable 
end-stage renal function who require HD. These subjects may have acceptable comorbid 
conditions in terms of safety and stability that are not anticipated to confound the study results. 
The subjects will be selected such that the mean and distribution of Group 1 is similar to the 
mean and distribution of subjects enrolled in Group 2 for age, sex, and body mass index, as far as 
possible. 
3.3. 
Selection of Doses in the Study 
Avacopan has been approved as an adjunctive treatment of adult subjects with severe active 
ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in 
combination with standard therapy including glucocorticoids. The recommended dosage is 
) twice daily, with food. 
For this study, a single dose of 
 is considered adequate to evaluate the pharmacokinetics 
and safety in subjects with normal renal function and in subjects with ESRD requiring HD. 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria prior to enrollment unless otherwise stated. 
Check-in with regards to inclusion criteria applies to Check-in on Period 1 Day -1 only. 
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1. Subject has provided informed consent before initiation of any study-specific 
activities or procedures. 
2. Male or female subjects, between 18 and 75 years of age (inclusive) at the time of 
Screening. 
3. Body mass index between 18 and 40 kg/m2 at the time of Screening. 
4. Subjects eligible for Group 1 (normal renal function) should be in good health, 
determined by no clinically significant findings from medical history, physical 
examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) as assessed by the 
Investigator (or designee). 
5. For subjects in Group 1 (normal renal function), systolic blood pressure (BP) 90 and 
150 mmHg and diastolic BP 50 and 100 mmHg, and pulse rate 40 and 110 
bpm at Screening. One repeat BP measurement will be allowed at Screening and 
Check-in. 
6. For subjects in Group 2 (ESRD requiring HD), vital signs, physical examinations, and 
12-lead ECGs (reporting heart rate, PR, QRS, QT, and QT interval corrected for heart 
rate using Fridericia’s method [QTcF]), including waveform, are normal or clinically 
acceptable to the Investigator, if outside the normal range. 
7. For subjects in Group 2 (ESRD requiring HD), laboratory test values (clinical 
chemistry and hematology) are consistent with the level of renal impairment and 
clinically acceptable to the Investigator. 
8. For subjects in Group 2 (ESRD requiring HD), nonhypertensive subjects or subjects 
with treated, stable hypertension, as defined by systolic BP not exceeding 170 mmHg 
and diastolic BP not exceeding 100 mmHg at Screening and Check-in. 
9. Eligible subjects will be classified based on established need for renal replacement 
therapy and eGFR, calculated using the MDRD formula. Assignment will be based on 
eGFR at Screening. 
a. Group 1 (normal renal function): eGFR 90 mL/min and no history of renal 
disease. 
b. Group 2 (ESRD requiring HD): eGFR 15 mL/min and receiving HD. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria prior to 
enrollment unless otherwise stated. Check-in with regards to exclusion criteria applies to 
Check-in on Period 1 Day -1 only. 

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All Subjects: 
10. History of uncontrolled or unstable cardiovascular, respiratory, hepatic, 
gastrointestinal, endocrine, hematopoietic, psychiatric, or neurological disease, 
defined as having been hospitalized within 28 days before Check-in, major surgery 
within 6 months before Check-in, or otherwise unstable in the judgment of the 
Investigator and/or Medical Monitor (e.g., risk of complications or adverse events 
unrelated to study participation), or evidence of rapidly deteriorating renal function. 
11. History or evidence, at Screening or Check-in, of clinically significant disorder, 
condition, or disease not otherwise excluded that, in the opinion of the Investigator 
(or designee), would pose a risk to subject safety or interfere with the study 
evaluation, procedures, or completion. 
12. Total white blood cell count is below the lower limit of normal at Screening or 
Check-in. 
13. Significant infection (in the judgment of the Investigator and/or Medical Monitor) 
within 28 days before Check-in. 
14. Prior infection with or exposure to tuberculosis, or travel to areas of endemic 
tuberculosis or endemic mycoses within the past 6 months. 
15. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase or 
alanine aminotransferase  the upper limit of normal for Group 1 (normal renal 
function) and 2 times the upper limit of normal for Group 2 (ESRD requiring HD). 
16. History or evidence, at Screening or Check-in, of poorly controlled diabetes 
(regardless of type), based on hemoglobin A1C of 10. 
17. Second-degree atrioventricular block or third degree atrioventricular block at 
Screening or Check-in. 
18. Clinically significant hyperkalemia (defined by serum potassium concentration as 
5.5 mEq/L for Group 1 [normal renal function], 6 mEq/L for Group 2 [ESRD 
requiring HD]) at Screening or Check-in. Repeat testing and rescreening for screen 
failures will be permitted. 
19. Subjects who have a current, functioning organ transplant and/or are on 
immunosuppressants. 
20. Subjects on the national transplant list (United Network for Organ Sharing) at 
Screening who anticipate receiving an organ transplant within 4 months. 
21. Positive human immunodeficiency virus test. 
22. Positive hepatitis B or hepatitis C panel (including positive HBsAg and/or positive 
hepatitis C antibody) at Screening. Subjects whose results are compatible with prior 
hepatitis B infection (positive hepatitis B surface antibody, positive hepatitis B core 
antibody, or negative HBsAg) will be excluded. Subjects whose results are 

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compatible with prior hepatitis B vaccination (positive hepatitis B surface antibody, 
negative hepatitis B core antibody, negative HBsAg) may be included. 
23. History or evidence of clinically significant arrhythmia at Screening, including any 
clinically significant findings on the ECG taken at Check-in. 
24. History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, 
or duodenal ulceration, or bowel disease (including but not limited to peptic 
ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn’s disease, or irritable 
bowel syndrome); or a history of gastrointestinal surgery, other than uncomplicated 
appendectomy. 
25. History of hypersensitivity, intolerance, or allergy to avacopan or any of the 
excipients. 
26. Poor peripheral venous access. 
27. Currently taking a moderate or strong inducer of the CYP3A4 enzyme (e.g., 
carbamazepine, phenobarbital, phenytoin, or rifampin), or use of a strong CYP3A4 
inducer, within 5 half-lives or 14 days prior to Check-in (whichever is longer) and 
through EOS, unless deemed acceptable by the Investigator, Medical Monitor, and/or 
the Sponsor. 
28. Currently taking a moderate or strong inhibitor of the CYP3A4 enzyme (e.g., 
boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, 
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, 
saquinavir, telaprevir, telithromycin, or voriconazole), or use of a strong CYP3A4 
inhibitor, within 5 half-lives or 14 days prior to Check-in (whichever is longer) and 
through EOS, unless deemed acceptable by the Investigator, Medical Monitor, and/or 
the Sponsor. 
29. Use of any over-the-counter or prescription medications within 30 days or 5 half-lives 
(whichever is longer) before enrollment, with the below exceptions: 
a. Acetaminophen (paracetamol; up to 2 g/day) for analgesia will be allowed. 
b. Hormone replacement therapy (e.g., estrogen, thyroid treatments including 
levothyroxine [Synthroid, Levothroid, Levoxyl, and Unithroid], liothyronine 
[Cytomel], liotrix [Thyrolar], and natural thyroid [Armour Thyroid, Nature-throid, 
Westhroid]) will be allowed. 
c. Hormonal contraception will be allowed. 
d. Aside from strong inducers or inhibitors of CYP3A4, therapies for renal disease 
and treatments of comorbidities, such as hypertension, that have been stable for at 
least 3 months prior to study drug administration and deemed acceptable by the 
Investigator (or designee) and Medical Monitor to be given concurrently with 
avacopan during the study period are permitted. Minor adjustments in dose or 
formulation of medications used to treat renal disease and associated disorders 

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without significant change in clinical condition within the past 3 months are 
permitted. 
30. Consumption of foods and beverages containing poppy seeds, pomelos, or Seville 
oranges within 7 days prior to Check-in and consumption of foods and beverages 
containing grapefruit within 14 days prior to Check-in. 
31. All herbal medicines (e.g., St. John’s wort), vitamins, and supplements consumed by 
the subject within the 30 days prior to enrollment, unless deemed acceptable by the 
Investigator (or designee) and in consultation with the Sponsor. 
32. History of alcoholism or drug/chemical abuse within 1 year prior to Check-in. 
33. Alcohol consumption from 48 hours prior to Check-in. 
34. Regular alcohol consumption of 14 units per week for males and 7 units for 
females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 
5 oz (150 mL) wine. 
35. Significant use of tobacco- or nicotine-containing products (e.g., ½ pack of 
cigarettes per day) within 3 months prior to Check-in through EOS. 
36. Positive alcohol test at Check-in or positive drug screen (confirmed by repeat) at 
Screening or Check-in, that is not otherwise explained by permitted concomitant or 
prescription medications. Group 2 (ESRD requiring HD) subjects will be permitted 
on study if drug screen is positive for opiates or benzodiazepines. Subjects who 
screen positive for tetrahydrocannabinol/ 
cannabinoids will be excluded. At Check-in, a positive alcohol test may not be 
repeated.  
37. Consumption of caffeine-containing foods and beverages within 48 hours prior to 
Check-in. 
38. Female subjects with a positive pregnancy test at Screening or Check-in. 
39. Female subjects lactating/breastfeeding or who plan to breastfeed during the study 
through 60 days after administration of investigational product. 
40. Unwilling to adhere to contraceptive requirements through 60 days after 
administration of investigational product. 
41. Unwilling to abstain from sperm donation and ovum donation through 60 days after 
administration of investigational product. 
42. Male subjects with a female partner of childbearing potential and not willing to 
inform his partner of his participation in this clinical study. 
43. Male subjects with a pregnant partner or partner planning to become pregnant who 
are unwilling to practice sexual abstinence or use contraception while the subject is 
participating in the study from Check-in until 60 days after administration of 
investigational product. 

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44. Subject has received a dose of an investigational drug within the past 90 days or 
5 half-lives, whichever is longer, prior to Check-in. 
45. Have previously completed or withdrawn from this study or any other study 
investigating avacopan, or have previously received the investigational product.  
46. Donation of blood from 90 days prior to Check-in, plasma from 2 weeks prior to 
Check-in, or platelets from 6 weeks prior to Check-in. 
47. Unwilling to abide with study restrictions. 
48. Subjects who, in the opinion of the Investigator (or designee), should not participate 
in this study. 
Subjects in Group 1 (normal renal function) are excluded if: 
49. History of malignancy of any type, with the exception of the following: in situ 
cervical cancer or surgically excised non-melanomatous skin cancers more than 
5 years before receiving avacopan. 
50. A QTcF 450 msec in males or 470 msec in females or history/evidence of long QT 
syndrome at Screening or Check-in. 
51. A history of renal disease or renal injury as indicated by medical history or an 
abnormal renal function profile at Screening or Check-in. 
Subjects in Group 2 (ESRD requiring HD) are excluded if: 
52. Child-Pugh classification of Class A, B, or C, indicating hepatic impairment assessed 
at Screening and Check-in (Appendix 10). 
53. Active malignancy of any type. Subjects with a history of malignancy that has been 
eradicated with supporting medical documentation indicating that there is no residual 
malignancy detected in the past 2 years will be allowed.  
54. A change in disease status within 30 days of Screening, as documented by the 
subject’s medical history, deemed clinically significant by the Investigator. 
55. A QTcF 470 msec in males or 480 msec in females. 
4.3. 
Screen Failures and Rescreening 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently enrolled in the study because they do not meet eligibility requirements. A minimal 
set of screen failure information may be collected that includes demography, screen failure 
details, eligibility criteria, medical history, prior therapies, and any serious adverse events. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened only once.  

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terminate the Investigator's participation in the study according to the Clinical Trial Agreement. 
The Investigator is to notify the Institutional Review Board (IRB) in writing of the study's 
completion or early termination and send a copy of the notification to the Sponsor. The Sponsor 
reserves the unilateral right, at its sole discretion, to determine whether to supply investigational 
product and by what mechanism, after termination of the study. 
In addition, the study may be terminated by the Sponsor at any time and for any reason. If the 
Sponsor decides to terminate the study, they will inform the Investigator as soon as possible. 
4.7. 
Discontinuation of Study Treatment (Group 2 only) 
Subjects (or a legally acceptable representative) can decline to continue receiving investigational 
product and/or other protocol-required therapies or study procedures at any time during the study 
but continue participation in the study. If this occurs, the Investigator is to discuss with the 
subject the appropriate processes for discontinuation from investigational product or other 
protocol-required therapies and must discuss with the subject the possibilities for continuation of 
the Schedule of Assessments (Appendix 9) including different options of follow-up (e.g., in 
person, by phone/mail, through family/friends, in correspondence/communication with other 
treating physicians, from the review of medical records) and collection of data, including 
endpoints, Adverse Events, Serious Adverse Events and must document this decision in the 
subject’s medical records. Subjects who have discontinued investigational product and/or other 
protocol-required therapies or study procedures should not be automatically removed from the 
study. Whenever safe and feasible, it is imperative that subjects remain on study to ensure safety 
surveillance and/or collection of outcome data. 
Reasons for removal from protocol-required investigational product(s) or procedural assessments 
include any of the following: 
 
Decision by sponsor 
 
Lost to follow-up 
 
Death 
 
Adverse event 
 
Subject request 
 
Ineligibility determined 
 
Protocol deviation 
 
Noncompliance 
 
Requirement for alternative therapy 
 
Pregnancy 
 
Protocol-specified criteria 

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5. STUDY TREATMENTS 
Study treatment is defined as any investigational product, non-investigational product, placebo, 
or medical device intended to be administered to a study subject according to the study protocol. 
Note that in several countries, investigational product and non-investigational product are 
referred to as investigational medicinal product and non-investigational medicinal product, 
respectively. 
5.1. 
Investigational Product 
The IMP will be supplied by the Sponsor. Detailed information regarding the storage, 
preparation, destruction, and administration of IMP will be provided.  
All supplies of investigational product, both bulk and subject-specific, will be stored in 
accordance with the manufacturer’s instructions or pharmacy instructions. Until dispensed to the 
subjects, the investigational and non-investigational products will be stored at the study site in a 
location that is locked with restricted access. 
The IMP will be stored according to the instructions on the label at the CRU. 
Table 2: 
Investigational Product 
Study Treatment Name 
Investigational Medicinal Product: 
Avacopan 
Unit Strength and Formulation 
 Immediate Release Hard Gelatin Capsule 
Dose 
) 
Route of Administration 
Oral 
Accountability 
The quantity administered, date administered, and lot 
number of investigational product are to be recorded on the 
appropriate Case Report Form.  
Dosing Instructions 
The Investigator/designee will administer the treatment after 
the completion of all predose procedures, under fed 
conditions. A standardized hemodialysis-friendly 
standardized meal will be provided to all subjects on Day 1. 
The dose should be taken within 30 minutes of the start of 
the meal. 
 should be taken with 
approximately 8 ounces (240 mL) of water. Capsules should 
not be broken or chewed. 
Except as part of the dose administration, subjects will restrict their consumption of water for 
1 hour prior to dosing and for 1 hour after dosing; at all other times during the study, subjects 
may consume water as desired. Subjects will fast for at least 4 hours postdose. 
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Subjects will be dosed while standing and will not be permitted to lie supine for 2 hours after 
administration of IMP, except as necessitated by the occurrence of an adverse event(s) and/or 
study procedures. 
5.2. 
Investigational Product Administration 
Subjects in Group 1 will have 1 dose administration each of 
 of avacopan and subjects in 
Group 2 will have two dose administrations each of 
 of avacopan. Subjects will be dosed 
in the order that they were enrolled. Subjects will receive all doses under supervision of the site 
staff. 
5.3. 
Treatment of Overdose 
For this study, any dose of avacopan greater than 
 will be considered an overdose. The 
effects of overdose of avacopan are not known. In case of overdose, consultation with the 
Medical Monitor is recommended for prompt reporting of clinically apparent or laboratory 
adverse events possibly related to overdosage, and to discuss further management of the subject. 
5.3.1. 
Medical Devices  
No investigational medical devices will be used in this study. 
Other non-investigational medical devices may be used in the conduct of this study as part of 
standard care. Non-Amgen non-investigational medical devices (e.g., syringes, sterile needles), 
that are commercially available are not usually provided or reimbursed by the Sponsor (except, 
for example, if required by local regulation). The Investigator will be responsible for obtaining 
supplies of these devices. 
5.3.2. 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
drug, combination product, or device after it is released for distribution to market or clinic by 
either (1) Amgen or (2) distributors or partners for whom Amgen manufactures the material. 
This includes all components distributed with the drug, such as packaging drug containers, 
delivery systems, labeling, and inserts. 
This includes any investigational/non-investigational product(s), provisioned and/or 
repackaged/modified by Amgen.  
Any product complaint(s) associated with an investigational product(s) supplied by Amgen are to 
be reported. 
5.4. 
Randomization 
This is a nonrandomized study. The study has a fixed treatment sequence. 
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5.5. 
Blinding 
This is an open-label study. 
5.6. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance:  
 When subjects are dosed at the site, they will receive avacopan directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded on the 
eCRF.  
 Immediately after dose administration, visual inspection of the mouth and hands will be 
performed for each subject. 
 At each dosing occasion, a predose and postdose inventory of IMP will be performed. 
5.7. 
Drug Accountability 
The Investigator (or designee) will maintain an accurate record of the receipt of avacopan 
capsules received. In addition, an accurate drug disposition record will be kept, specifying the 
amount dispensed to each subject and the date of dispensing. This drug accountability record will 
be available for inspection at any time. At the completion of the study, the original drug 
accountability record will be available for review by the Sponsor upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused assembled 
unit doses will be retained until completion of the study. 
At the completion of the study, all unused avacopan will be returned to the Sponsor, retained at 
the study site, or disposed of by the study site, per the Sponsor’s written instructions. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects with normal renal function will refrain from use of any prescription or nonprescription 
medications/products during the study until the EOS visit, unless the Investigator (or designee) 
and/or Sponsor have given their prior consent.  
For renal-impaired subjects, treatment with chronic stable medications (for at least 3 months 
prior to study drug administration with the exceptions of minor changes in dose or formulation 
without change in clinical condition) necessary for maintaining the clinical status of the subject 
will be permitted if prescribed by the subject’s personal physician and approved by the Medical 
Monitor and Investigator, in consultation with the Sponsor as needed. Except for concomitant 

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therapies associated with HD sessions, administration of medications should be withheld for at 
least 4 hours after study drug administration as clinically appropriate, unless needed for 
treatment of an adverse event, at the discretion of the Investigator. Throughout the study, 
Investigators may prescribe any concomitant medications or treatments deemed necessary to 
provide adequate supportive care while avoiding those listed in the exclusion criteria. 
Acetaminophen (paracetamol) (2 g/day); hormone replacement therapy (e.g., estrogen and 
thyroid treatments including levothyroxine [Synthroid, Levothroid, Levoxyl, Unithroid], 
liothyronine [Cytomel], Liotrix [Thyrolar], and natural thyroid [Armour Thyroid, Nature-throid, 
Westhroid]); or oral, implantable, transdermal, injectable, or intrauterine contraceptives are 
acceptable concomitant medications. The administration of any other concomitant medications 
during the study is prohibited without prior approval of the Investigator (or designee), unless its 
use is deemed necessary for treatment of an adverse event/serious adverse event. Any medication 
taken by a subject during the course of the study and the reason for its use will be documented in 
the source data. 
6.2. 
Diet 
Subjects will be fasted overnight (at least 8 hours) before collection of blood samples for clinical 
laboratory evaluations. While confined at the study site, subjects will receive a diet provided by 
the site at scheduled times that do not conflict with other study-related activities. No outside food 
or beverage will be permitted during confinement. 
On dosing days (Day 1 for Group 1 and Day 1 of Periods 1 and 2 for Group 2), subjects will 
receive a standardized breakfast prior to study drug administration. The standardized breakfast 
will include approximately 215 fat calories, approximately 320 carbohydrate calories, 
approximately 125 protein calories, and approximately 1220 mg of sodium. 
Refer to Section 5 and Table 2 for diet requirements/restrictions on applicable days of study 
treatment and/or PK assessments. 
Foods and beverages containing poppy seeds, pomelos, or Seville oranges will not be allowed 
from 7 days prior to Check-in until EOS visit. Foods and beverages containing grapefruit will not 
be allowed from 14 days prior to Check-in until EOS visit. 
Caffeine-containing foods and beverages will not be allowed from 48 hours before Check-in 
until EOS visit. 
Consumption of alcohol will not be permitted from 48 hours prior to Check-in until EOS visit. 
6.3. 
Smoking 
Subjects will not be permitted significant use of tobacco- or nicotine-containing products (e.g., 
 ½ pack of cigarettes per day) within 3 months prior to Check-in through EOS. 

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6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before Check-in until the 
EOS visit. Subjects will otherwise maintain their normal level of physical activity during this 
time (i.e., will not begin a new exercise program nor participate in any unusually strenuous 
physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 90 days prior to Check-in, plasma 
from 2 weeks prior to Check-in, and platelets from 6 weeks prior to Check-in until 3 months 
after the EOS visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving consideration to appropriate posture conditions, practical restrictions, and 
the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. Unless otherwise 
specified in the Schedule of Assessments, the order of priority for scheduling procedures around 
a timepoint is: 
 predose safety assessments 
 
predose/trough PK blood samples 
 
dosing 
 
PK blood samples (postdose) 
 
postdose safety assessments (ECGs will be scheduled before vital signs measurements) 
 
any other procedures. 
Where activities at a given timepoint coincide, consideration must be given to ensure that the 
following order of activities is maintained: ECGs, vital signs, and safety laboratory assessments. 
7.1. 
Pharmacokinetic Assessments 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples will be collected by venipuncture or cannulation at the times indicated in the 
Schedule of Assessments in Appendix 9. Arterial and venous PK samples may be collected from 
the HD catheter or arteriovenous fistula as appropriate. 
Dialysate samples will be collected as specified in Appendix 9. Procedures for collection, 
processing, and shipping of PK blood samples will be detailed in a separate document.  

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For Group 2 Period 1, a sample of dialysate will be collected on Day 1 at 0.5, 1, 2, and 3 hours 
after the start of HD and after HD is complete for drug concentration analysis. The entire 
dialysate volume, blood flow, and dialysate flow during HD will be recorded for each timepoint, 
and the make and model of the dialyzer will be recorded. 
Any blood sample collected according to the Schedule of Assessments (Appendix 9) can be 
analyzed for any of the tests outlined in the protocol and for any tests necessary to minimize 
risks to study subjects. This includes testing to ensure analytical methods produce reliable and 
valid data throughout the course of the study. This can also include, but is not limited to, 
investigation of unexpected results, incurred sample reanalysis, and analyses for method transfer 
and comparability.  
7.1.2. 
Analytical Methodology 
Plasma concentrations of avacopan and M1 metabolite will be determined using validated 
analytical procedures. Dialysate concentrations of avacopan and protein binding assessments will 
be determined using qualified methods. Specifics of the analytical method will be provided in a 
separate document. 
7.2. 
Safety and Tolerability Assessments 
7.2.1. 
Adverse Events and Serious Adverse Events: Time period and Frequency for 
Collecting and Reporting Safety Event Information 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
Adverse Events and Serious Adverse Events are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF to EOS. 
Subjects will be observed for any signs or symptoms and asked about their condition by open 
questioning, such as “How have you been feeling since you were last asked?”, at least once each 
day while resident at the study site and at each study visit. Subjects will also be encouraged to 
spontaneously report Adverse Events and Serious Adverse Events occurring at any other time 
during the study. 
Adverse Events 
The adverse event grading scale to be used in this study is described in Appendix 1. 
The Investigator is responsible for ensuring that all adverse events observed by the Investigator 
or reported by the subject that occur after first dose of investigational product through the 
30 days after the last day of the dosing interval of investigational product, whichever is later are 
reported using the Events Case Report Form (CRF). 

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Serious Adverse Events 
The Investigator is responsible for ensuring that all serious adverse events observed by the 
Investigator or reported by the subject that occur after signing of the informed consent through 
30 days after dosing of investigational product orEOS visit, whichever is later, are reported using 
the appropriate eCRF and reported on the paper-based Serious Adverse Event Report Form 
(described in Appendix 1). 
All serious adverse events will be collected, recorded, and reported to the Sponsor within 
24 hours of the Investigator’s knowledge of the event. The Investigator will submit any updated 
Serious Adverse Event data to the Sponsor within 24 hours of it being available. 
Since the criteria of the Common Terminology Criteria for Adverse Events (CTCAE) grading 
scale differs from the regulatory criteria for serious adverse events, if adverse events correspond 
to Grade 4 CTCAE toxicity grading scale criteria (e.g., laboratory abnormality reported as Grade 
4 without manifestation of life-threatening status), it will be left to the Investigator’s judgment to 
also report these abnormalities as serious adverse events. For any adverse event that applies to 
this situation, comprehensive documentation of the event’s severity must be recorded in the 
subject medical records. 
Serious Adverse Events After the Protocol-Required Reporting Period  
After EOS, there is no requirement to actively monitor study subjects after the study has ended 
with regards to study subjects treated by the Investigator. However, if the Investigator becomes 
aware of serious adverse events (regardless of causality), then these serious adverse events will 
be reported to Amgen within 24 hours following the Investigator’s awareness of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the Sponsor’s safety database as clinical trial cases and handled accordingly 
based on relationship to investigational product.  
If further safety-related data is needed to fulfill any regulatory reporting requirements for a 
reportable event, then additional information may need to be collected from the subject’s records 
after the subject ends the study. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious adverse 
events. Open-ended and non-leading verbal questioning of the subject is the preferred method to 
inquire about adverse event occurrence. 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial adverse event/serious adverse event report, the Investigator is required to 
proactively follow each subject at subsequent visits/contacts. All adverse events and serious 

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adverse events will be followed, where possible, until resolution, stabilization, until the event is 
otherwise explained, or the subject is Lost to Follow-up. This will be completed at the 
Investigator’s (or designee’s) discretion. 
All new information for previously reported serious adverse events must be sent to Amgen 
within 24 hours following knowledge of the new information. If specifically requested, the 
Investigator may need to provide additional follow-up information, such as discharge summaries, 
medical records, or extracts from the medical records. Information provided about the serious 
adverse event must be consistent with that recorded on the eCRF. 
Regulatory Reporting Requirements for Serious Adverse Events 
If the subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to the Sponsor. 
Prompt notification by the Investigator to the Sponsor of serious adverse events is essential so 
that legal obligations and ethical responsibilities towards the safety of subjects and the safety of a 
study treatment under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRBs/Independent Ethics Committees, and Investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
Amgen will prepare a single Development Safety Update Report (also referred to as Annual 
Safety Report in the European Union) for the Amgen Investigational Product. To ensure that 
consolidated safety information for the study is provided, this single Development Safety Update 
Report will also include appropriate information on any other investigational products used in 
the clinical study, if applicable. 
An Investigator who receives an individual safety report describing a serious adverse event or 
other specific safety information (e.g., summary or listing of serious adverse events) from the 
Sponsor will file it along with the IB and will notify the IRB, if appropriate according to local 
requirements. 
Safety Monitoring Plan 
Subject safety will be routinely monitored as defined in the Sponsor’s safety surveillance and 
signal management processes. 

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Other Safety Findings/Special Situations 
Medication errors, misuse or abuse of the investigational product is subject to the same reporting 
obligation as adverse events. Therefore, the following procedures must be followed:  
 All medication errors, misuse, or abuse of the investigational product, whether or not the 
Other Safety Finding (OSF)/Special Situation (SS) is accompanied by a non-serious 
adverse event or a serious adverse event, as determined by the Investigator, the OSF/SS 
must be collected and recorded on the OSF/SS CRF. 
 If there are any resulting clinical signs, symptoms, or sequelae, the corresponding non-
serious adverse event or serious adverse event must also be collected and recorded on the 
Events CRF.  
 All medication errors, misuse, or abuse when associated with a serious adverse event 
must also be reported to Amgen or designee immediately and no later than 24 hours of 
the Investigator’s awareness of the OSF/SS - medication error, misuse, or abuse by 
submitting Serious Adverse Event Report Form. 
Further details and definitions regarding OSF/ SS - medication errors, misuse, and abuse, can be 
found in Appendix 1. 
Pregnancy and Lactation 
Details of all pregnancies and/or lactation in female subjects and, if indicated, female partners of 
male subjects will be collected after the start of study treatment and until 60 days after dosing of 
investigational product. 
If a pregnancy is reported, the Investigator is to inform Amgen immediately and no later than 
24 hours of learning of the pregnancy and/or lactation and is to follow the procedures outlined in 
Appendix 4. Amgen Global Patient Safety will follow-up with the Investigator regarding 
additional information that may be requested. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Appendix 4. 
Pregnancy Testing 
A highly sensitive (urine or serum) pregnancy test should be completed at screening and within 
7 days of initiation of investigational product for females of childbearing potential.  
Note: Females who have undergone a bilateral tubal ligation/occlusion should have pregnancy 
testing per protocol requirements. (If a female subject, or the partner of a male subject, becomes 

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pregnant it must be reported on the Pregnancy Notification Form, see Figure 6). Refer to 
Appendix 3 for contraceptive requirements. 
A pregnancy test will be performed at the end of the study. 
Additional on-treatment pregnancy testing may be performed at the Investigator’s discretion or 
as required per local laws and regulations.  
7.2.2. 
Clinical Laboratory Evaluations 
Blood samples will be collected for clinical laboratory evaluations (including clinical chemistry, 
hematology, and serology) at the times indicated in the Schedule of Assessments in Appendix 9. 
Urine samples will be collected for Group 1 only for clinical laboratory evaluations (including 
clinical chemistry, hematology, urinalysis, and serology) at the times indicated in the Schedule of 
Assessments in Appendix 9. Clinical laboratory evaluations are listed in Appendix 2. 
The Investigator is responsible for reviewing laboratory test results and recording any clinically 
relevant changes occurring during the study in CRF/eCRF. The Investigator must determine 
whether an abnormal value in an individual study subject represents a clinically significant 
change from the subject’s baseline values. In general, abnormal laboratory findings without 
clinical significance (based on the Investigator’s judgment) are not to be recorded as adverse 
events. However, laboratory value changes that require treatment or adjustment in current 
therapy are considered adverse events. Where applicable, clinical sequelae (not the laboratory 
abnormality) are to be recorded as the adverse event. 
Subjects in Group 1 will provide urine samples for drugs of abuse screen and will undergo an 
alcohol breath test at the times indicated in the Schedule of Assessments in Appendix 9. Subjects 
in Group 2 will provide a blood or saliva sample for drugs of abuse screen and will undergo an 
alcohol breath test at the times indicated in the Schedule of Assessments in Appendix 9. For all 
female subjects, a pregnancy test and follicle-stimulating hormone (FSH) screen for 
postmenopausal women will be performed at the times indicated in the Schedule of Assessments 
in Appendix 9.  
An Investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.2.3. 
Vital Signs 
Seated or supine BP, seated or supine pulse rate, respiratory rate, and oral body temperature will 
be assessed at the times indicated in the Schedule of Assessments in Appendix 9. Vital signs may 
also be performed at other times if judged to be clinically appropriate. 
All measurements will be performed singly and repeated once if outside the relevant clinical 
reference range. 

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Subjects must be seated or supine for at least 5 minutes before BP and pulse rate measurements. 
When vital signs are scheduled at the same time as blood draws, the blood draws will be 
obtained at the scheduled timepoint, and the vitals will be obtained as close to the scheduled 
blood draw as possible, but prior to the blood draw. 
Vital signs for subjects will be taken consistently for each subject in either the seated or supine 
position. If the subject is unable to be in the supine position, the subject should be in the most 
recumbent position possible. The position selected for a subject should be the same that is used 
throughout the study and documented on the vital signs eCRF. 
7.2.4. 
12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at least 
5 minutes at the times indicated in the Schedule of Assessments in Appendix 9. Single 12-lead 
ECGs will be repeated twice, and an average taken of the 3 readings, if either of the following 
criteria apply: 
 QTcF is 500 ms 
 QTcF change from the baseline (predose) is 60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically appropriate. 
The Investigator (or designee) will perform a clinical assessment of each 12-lead ECG and 
initiate further work-up or intervention as necessary. 
7.2.5. 
Physical Examination 
Physical examination will be performed and will include a neurological examination (breast, 
rectal, and genital examination are not required). Neurologic examination will include evaluation 
of mental status/cognition/mood/affect, gross and fine motor, sensory, cranial nerves, 
coordination, and deep tendon reflexes. Physical examination findings should be recorded on the 
appropriate CRF (e.g., medical history, treatment-emergent adverse event). Physical 
examinations will be performed at the timepoints specified in the Schedule of Assessments in 
Appendix 9. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
The sample size for this study is based on studies of similar design and is considered adequate 
for evaluation of the study objectives. 
Approximately 12 subjects are planned to be enrolled in this study. Approximately 6 subjects 
will be enrolled in each group. 

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8.2. 
Analysis Populations 
8.2.1. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of avacopan and have 
evaluable PK data. A subject may be excluded from the PK summary statistics and statistical 
analysis if the subject has an adverse event of vomiting that occurs at or before 2 times median 
time to maximum concentration or diarrhea within 24 hours of dosing.  
8.2.2. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of avacopan and have 
at least 1 postdose safety assessment. 
If a subject has a serious adverse event prior to dosing, reporting of the serious adverse event will 
be included with the safety population. 
8.3. 
Pharmacokinetic Analyses 
Arithmetic mean, coefficient of variation (CV), standard deviation, median, minimum, 
maximum, and number of observations will be calculated for the PK parameters for each renal 
function group. Geometric mean and geometric CV will be provided for all PK parameters 
except tmax. Median, minimum, maximum, and number of observations will be calculated for 
tmax. 
The primary statistical analysis will estimate the relationship between the PK of avacopan and 
eGFR estimated by the MDRD equation. In addition, a relationship between the PK of M1 and 
the eGFR may also be evaluated. 
The PK parameters Cmax, tmax, apparent plasma terminal elimination half-life, AUCinf, AUC0-48, 
AUClast, apparent clearance (CL/F), fraction of unbound drug (fu), apparent volume of 
distribution (Vz/F), extraction ratio for HD (ERD), and CLD will be determined, as appropriate, 
by using noncompartmental methods. Additional PK parameters may be determined as 
appropriate. 
Ratios (test/reference) for the model-estimated Cmax, AUC0-48 (calculated for Group 2 Period 2), 
and AUCinf (test) relative to the group with normal renal function (reference) will be generated, 
along with 90 confidence intervals. 
For subjects in Group 2, the PK parameters Cmax, tmax, AUC0-48, and AUC0-last will be determined 
by using noncompartmental methods for doses administered. For subjects in Group 2 Period 1, a 
sample of dialysate will be collected on Day 1 at 0.5, 1, 2, and 3 hours. In addition, to support 
determination of avacopan clearance by HD, AUClast will be determined from the arterial and 
venous plasma samples during HD (for Group 2 Period 1). The ratios (test/reference) of central 

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values and 90 CIs will be calculated for log-transformed Cmax and AUC values on HD day 
(Group 2 Period 1, test) compared to non-HD day (Group 2 Period 2, reference). 
Specific details will be presented in the Statistical Analysis Plan for this study. 
8.4. 
Safety Analysis 
The number and percentage of subjects reporting any adverse events will be tabulated by 
Medical Dictionary for Regulatory Activities system organ class and preferred term. Tables of 
fatal adverse events, serious adverse events, adverse events leading to withdrawal from 
investigational product, and treatment-emergent adverse events will also be provided. Subject-
level data may be provided instead of tables if the subject incidence is low. 
Clinical laboratory tests, ECG, and vital signs will be summarized. 
8.5. 
Interim Analysis 
No interim analyses are planned for this study.  
9. REFERENCES 
1. Amgen. Avacopan – Current Investigator’s Brochure.  
2. TAVNEOS (avacopan) capsules, for oral use. Highlights of Prescribing Information.  
3. Tavneous (Avacopan). Summary of Product Characteristics. Vifor Fresenius Medical Care 
Renal Pharma UK Ltd. 30 Aug 2023.  
4. US Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research. 2024. Guidance for industry: Pharmacokinetics in Patients 
with Impaired Renal Function - Study Design, Data Analysis, and Impact on Dosing. 
 

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10. APPENDICES 

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Other Safety Findings/Special Situations: Medication Errors, Misuse or Abuse 
All medication errors, misuse or abuse of the investigational product are subject to the 
same reporting obligation as adverse events and must be collected and recorded on the 
Other Safety Findings (OSF)/Special Situations (SS) case report form (CRF). If there 
are any resulting clinical signs, symptoms or sequelae, the corresponding non-serious 
adverse event and serious adverse event must also be collected and recorded on the 
Events CRF.   
All medication errors, misuse, or abuse when associated with a serious adverse event 
must also be reported to Amgen or designee immediately and no later than 24 hours of 
Investigator’s awareness of the OSF/SS - medication error, misuse or abuse by 
submitting the paper-based Serious Adverse Event Report Form. 
Other Safety 
Finding/Special Situation 
Collected and Recorded 
on the Other Safety 
Findings (OSF)/Special 
Situations (SS) Case 
Report Form (CRF)  
Primary Reporting 
Method:  
Reported/submitted on 
the paper-based Serious 
Adverse Event Report 
Form to Amgen or 
designee immediately and 
no later than 24 hours of 
Investigator’s awareness 
Medication Error 
All (regardless of 
whether 
associated with an 
adverse event/serious 
adverse event) 
Only if associated with a 
serious adverse event  
Misuse 
All (regardless of 
whether associated with 
an adverse event/serious 
adverse event)  
Only if associated with a 
serious adverse event  
Abuse 
All (regardless of 
whether associated with 
an adverse event/serious 
adverse event) 
Only if associated with a 
serious adverse event  
 
 
Medication Error: A medication error is an unintended failure 
in the drug treatment process that leads to, or has the potential 
to lead to harm to the subject (e.g., mistake in the process of 

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medical records. In this case, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records before 
submission to the Sponsor. 
 The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the adverse event/serious 
adverse event.  

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Figure 5:  
Sample Serious Adverse Event Report Form  
 

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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis – Group 1 only: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Blood urea nitrogen 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate 
Potassium  
Sodium  
Total bilirubina 
Total CO2 (may be measured as 
bicarbonate) 
Total protein 
Uric acid 
Hematocrit  
Hemoglobin  
Hemoglobin A1Cb 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell (RBC) count 
RBC distribution width 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Bilirubin 
Blood 
Color and appearance 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination (if 
protein, leukocyte esterase, 
nitrite, or blood is positive) 
Serologyc: 
Drug screenb: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency virus 
(HIV-1 and HIV-2) antibodies 
and p24 antigen 
Including but not limited to:  
Amphetamines/ 
methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol/ 
cannabinoids 
Alcohol breath testd  
Follicle-stimulating hormone 
(postmenopausal females only)c 
Serum pregnancy test (human 
chorionic gonadotropin)e 
Urine pregnancy teste 
Other Tests: 
Coagulation panelb: 
Hepatotoxicity
only: 
International 
normalized 
ratio (INR)f 
Estimated 
glomerular 
filtration rate 
(eGFR)g 
International normalized ratio 
(INR) 
Prothrombin time (PT) 
Partial thromboplastin time 
(PTT) 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated. 
b Only analyzed at Screening and Check-in. 
c Only analyzed at Screening. 
d Alcohol breath test performed at Check-in only. Matrix for drug screen will be flexible, depending on the renal impairment 
status of the subject. 
e Performed in serum at Screening and in urine at all other times for females in Group 1. A positive urine pregnancy test will be 
confirmed with a serum pregnancy test. Serum pregnancy test will be done at all timepoints for subjects in Group 2 (end-stage 
renal disease [ESRD]). 
f International normalized ratio will be retested if hepatotoxicity is suspected. 
g Estimated glomerular filtration rate will be calculated by the Modification of Diet in Renal Disease (MDRD) equation. 
  MDRD formula (mL/min/1.73 m2)  175 x (serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.212 if African-American) 

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Appendix 3: Contraception Requirements 
All subjects must receive pregnancy prevention counseling and be advised of the risk to the fetus 
if they conceive a child during treatment and for 60 days after administration of the 
investigational product. 
Additional medications given during the study may alter the contraceptive requirements. The 
Investigator must discuss these contraceptive changes with the subject. 
Definitions Women of Childbearing Potential: premenopausal females who are anatomically 
and physiologically capable of becoming pregnant following menarche.  
Women of Non-Child-Bearing Potential: 
1. Surgically sterile: females who are permanently sterile via hysterectomy, bilateral 
salpingectomy, and/or bilateral oophorectomy by reported medical history and/or 
medical records. Surgical sterilization to have occurred a minimum of 6 weeks, or at 
the Investigator’s discretion, prior to Screening.  
2. Postmenopausal: Females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating hormone 
levels of  40 mIU/mL. The amenorrhea should not be induced by a medical 
condition such as anorexia nervosa, hypothyroid disease or polycystic ovarian 
disease, or by extreme exercise. It should not be due to concomitant medications that 
may have induced the amenorrhea such as oral contraceptives, hormones, 
gonadotropin-releasing hormones, anti-estrogens, or selective estrogen receptor 
modulators.  
Fertile male: males are considered fertile after puberty.  
Contraception Requirements 
Female Subjects  
Female subjects who are of nonchildbearing potential will not be required to use contraception. 
Female subjects of childbearing potential must be willing to use 2 methods (1 primary and 
1 secondary method) of birth control from the time of signing the Informed Consent Form (ICF) 
until 60 days after administration of the investigational product.  
Primary methods of contraception include:  
 hormonal injection (as prescribed)  
 combined oral contraceptive pill or progestin/progestogen-only pill associated with 
inhibition of ovulation (as prescribed) without supplementary iron (i.e. Loestrin Fe, Junel 
Fe, and Lo Loestrin Fe are prohibited) 
 combined hormonal patch (as prescribed)  

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 combined hormonal vaginal ring (as prescribed)  
 surgical method performed at least 3 months prior to the Screening visit:  
o Bilateral tubal ligation with confirmation of surgical success 
o Regulatory approved method of hysteroscopic bilateral tubal occlusion with 
confirmation of occlusion of the fallopian tubes 
 hormonal implant  
 hormonal or non-hormonal intrauterine device  
 vasectomized male partner (sterilization performed at least 90 days prior to the Screening 
visit, with verbal confirmation of surgical success, and the sole partner for the female 
subject).  
Secondary (barrier) methods of contraception include:  
 male condom with spermicide  
 female condom with spermicide  
 over-the-counter sponge with spermicide  
 cervical cap with spermicide (as prescribed)  
 diaphragm with spermicide (as prescribed).  
Female subjects should refrain from donation of ova from Check-in (Day -1) until 60 days after 
administration of the investigational product. 
Male Subjects:  
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (i.e., male condom with spermicide) in addition to a 
second method of acceptable contraception by female partner from Check-in until 60 days after 
administration of investigational product. Acceptable methods of contraception for female 
partners include:  
 hormonal injection  
 combined oral contraceptive pill or progestin/progestogen-only pill  
 combined hormonal patch  
 combined hormonal vaginal ring  
 surgical method (bilateral tubal ligation or regulatory approved method of hysteroscopic 
bilateral tubal occlusion)  
 hormonal implant  
 hormonal or non-hormonal intrauterine device  

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 over-the-counter sponge with spermicide  
 cervical cap with spermicide  
 diaphragm with spermicide.  
Male subjects are required to refrain from donation of sperm from Check-in until 60 days after 
administration of the investigational product.  
Sexual Abstinence  
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of 
risk associated with the study treatments) is an acceptable method of contraception. The 
reliability of sexual abstinence must be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, postovulation methods) and withdrawal are not acceptable methods of 
contraception. 
For subjects who practice true abstinence, subjects must be abstinent for at least 6 months prior 
to Screening and must agree to remain abstinent from the time of signing the ICF until 60 days 
after the EOS visit. 
If a subject who practices true abstinence at the time of signing the ICF becomes engaged in a 
heterosexual relationship, they must agree to use contraception as described previously from the 
time of signing the ICF until 60 days after the EOS visit. 
Same-sex Relationships 
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. 
If a subject who is in a same-sex relationship at the time of signing the ICF becomes engaged in 
a heterosexual relationship, they must agree to use contraception as described previously from 
the time of signing the ICF until 60 days after EOS.  

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Appendix 4: Collection of Pregnancy and Lactation Information 
Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking investigational product through 60 days after the last dose of 
investigational product. 
 Information will be recorded on the Pregnancy Notification Form (see Figure 6). The 
form must be submitted to Amgen Global Patient Safety within 24 hours of learning of a 
subject’s pregnancy. (Note: Sites are not required to provide any information on the 
Pregnancy Notification Form that violates the country or regions local privacy laws.) 
 After obtaining the female subject’s signed consent for release of pregnancy and infant 
health information, the Investigator will collect pregnancy and infant health information 
and complete the pregnancy questionnaire for any female subject who becomes pregnant 
while taking protocol-required therapies through 60 days after dosing of investigational 
product. This information will be forwarded to Amgen Global Patient Safety. Generally, 
infant Follow-up will be conducted up to 12 months after the birth of the child (if 
applicable). 
 Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for procedure.  
 While pregnancy itself is not considered to be an adverse event or serious adverse event, 
any pregnancy complication or elective termination of a pregnancy for medical reasons 
will be reported as an adverse event or serious adverse event. Abnormal pregnancy 
outcomes (e.g., spontaneous abortions, stillbirth, fetal death, congenital anomalies) will 
be reported as an adverse event or serious adverse event. Note that an elective 
termination with no information on a fetal congenital malformation or maternal 
complication is generally not considered an adverse event, but still must be reported to 
Amgen as a pregnancy exposure case. 
 Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the study treatment by the Investigator will be reported 
to Amgen Global Patient Safety as described in Appendix 1. While the Investigator is not 
obligated to actively seek this information in former study subjects, he or she may learn 
of a serious adverse event through spontaneous reporting.  
 Any female subject who becomes pregnant while participating will discontinue study 
treatment (see Section 4.7 for details). 
 
Male Subjects with Partners Who Become Pregnant or Were Pregnant at the Time of Enrollment 
 In the event a male subject fathers a child during treatment, and for an additional 60 days 
after dosing of investigational product. The information will be recorded on the 
Pregnancy Notification Form. The form (see Figure 6) must be submitted to Amgen 

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Global Patient Safety immediately and no later than 24 hours of the site’s awareness of 
the pregnancy. (Note: Sites are not required to provide any information on the Pregnancy 
Notification Form that violates the country or regions local privacy laws.) 
 Males whose partners become pregnant during treatment and for an additional 60 days 
after dosing of investigational product must practice sexual abstinence or use a condom 
through 60 days after dosing of investigational product and will be followed for safety 
until the end of study visit. 
 The Investigator will attempt to obtain a signed consent for release of pregnancy and 
infant health information directly from the pregnant female partner to obtain additional 
pregnancy information. 
 After obtaining the female partner’s signed consent for release of pregnancy and infant 
health information, the Investigator will collect pregnancy outcome and infant health 
information on the pregnant partner and her baby and complete the pregnancy 
questionnaires. This information will be forwarded to Amgen Global Patient Safety. 
 Generally, infant follow-up will be conducted up to 12 months after the birth of the child 
(if applicable).  
 Any termination of the pregnancy will be reported to Amgen Global Patient Safety 
regardless of fetal status (presence or absence of anomalies) or indication for procedure. 
Collection of Lactation Information 
 Investigator will collect lactation information on any female subject who breastfeeds 
while taking investigational product through 60 days after dosing of investigational 
product. 
 Information will be recorded on the Lactation Notification Form ( 
 Figure 7) and submitted to Amgen Global Patient Safety within 24 hours of the 
Investigator’s knowledge of event. 
 Study treatment will be discontinued if the female subject breastfeeds during the study. 
 With the female subject’s signed consent for release of mother and infant health 
information, the Investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while taking 
investigational product through 60 days after the last dose of investigational product.
With the female subject’s signed consent for release of mother and infant health information, the 
Investigator will collect mother and infant health information and complete the lactation 
questionnaire on any female subject who breastfeeds while taking protocol-required therapies 
through 60 days after discontinuing protocol-required therapies.

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Figure 6:  
Pregnancy Notification Form 
  

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Figure 7:  
Lactation Notification Form 
 
 

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Appendix 5: Sample Storage and Destruction 
When permitted by local regulations, any blood sample collected according to the Schedule of 
Assessments (Appendix 9) can be analyzed for any of the tests outlined in the protocol and for 
any tests necessary to minimize risks to study subjects. This includes testing to ensure analytical 
methods produce reliable and valid data throughout the course of the study. This can also 
include, but is not limited to, investigation of unexpected results, incurred sample reanalysis, and 
analyses for method transfer and comparability.  
All samples and associated results will be coded before being shipped from the site for analysis 
or storage. Samples will be tracked using a unique identifier that is assigned to the samples for 
the study. Results are stored in a secure database to ensure confidentiality.  

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Appendix 6: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines. 
 Applicable International Conference on Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines. 
 Applicable laws and regulations. 
The protocol, protocol amendments, Informed Consent Form (ICF), Investigator Brochure, and 
other relevant documents (e.g., advertisements) must be submitted to an Institutional Review 
Board (IRB) by the Investigator and reviewed and approved by the IRB before the study is 
initiated.  
Any amendments to the protocol will require IRB and regulatory authority (as locally required) 
approval before implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study subjects.  
The Investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB. 
 Notifying the IRB of serious adverse events or other significant safety findings as 
required by IRB procedures. 
 Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local regulations. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 
Informed Consent 
An initial sample ICF will be provided for the Investigator (or designee) to prepare the informed 
consent document to be used at his or her site. Updates to the sample ICF are to be 
communicated formally in writing from the Study Manager to the Investigator. The written ICF 
is to be prepared in the language(s) of the potential study participant population. 

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The Investigator or their delegated representative will explain to the subject, or their legally 
authorized representative, the aims, methods, anticipated benefits, and potential hazards of the 
study before any protocol-specific screening procedures or any investigational product(s) is/are 
administered and answer all questions regarding the study.  
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative (defined as an individual or other body authorized under applicable law 
to consent, on behalf of a prospective subject, to the subject’s participation in the clinical study) 
will then be required to sign a statement of informed consent that meets the requirements of 
21 CFR 50, local regulations, ICH guidelines, and the IRB or study site.  
The medical record must include a statement that written informed consent was obtained before 
the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
The acquisition of informed consent and the subject’s agreement or refusal of their notification 
of the primary care physician is to be documented in the subject’s medical records, and the ICF 
is to be signed and personally dated by the subject or a legally acceptable representative and by 
the person who conducted the informed consent discussion. Subject withdrawal of consent or 
discontinuation from study treatment and/or procedures must also be documented in the subject’s 
medical records. 
Subjects must be re-consented to the most current version of the ICF during their participation in 
the study.  
The original signed ICF is to be retained in accordance with institutional policy, and a copy of 
the ICF must be provided to the subject or the subject’s legally authorized representative.  
If a potential subject is illiterate or visually impaired and does not have a legally acceptable 
representative, the Investigator must provide an impartial witness to read the ICF to the subject 
and must allow for questions. Thereafter, both the subject and the witness must sign the ICF to 
attest that informed consent was freely given and understood. (Refer to ICH GCP guideline, 
Section 4.8.9.) 
A subject who is rescreened is not required to sign another ICF if the rescreening occurs within 
21 days from the previous ICF signature date and the same version of the ICF is in use at the 
time of rescreening. 
Subject Data Protection 
The Investigator must ensure that the subject’s confidentiality is maintained for documents 
submitted to the Sponsor. 

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Subjects will be assigned a unique identifier by the Sponsor (or designee). Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.  
On the electronic Case Report Form (eCRF) demographics page, in addition to the unique 
subject identification number (Section 4.4), include the age at time of enrollment. 
For serious adverse events reported to the Sponsor (or designee), subjects are to be identified by 
their unique subject identification number (Section 4.4), (for faxed reports, in accordance with 
local laws and regulations), and age (in accordance with local laws and regulations). 
Documents that are not submitted to the Sponsor (e.g., signed ICFs) are to be kept in confidence 
by the Investigator, except as described below. 
In compliance with ICH GCP Guidelines, it is required that the Investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and the IRB direct 
access to review the subject’s original medical records for verification of study-related 
procedures and data. Direct access includes examining, analyzing, verifying, and reproducing 
any records and reports that are important to the evaluation of the study.  
The Investigator is obligated to inform and obtain the consent of the subject to permit such 
individuals to have access to their study-related records, including personal information. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential information of the 
Sponsor, Amgen Inc. The Investigator (or designee) agrees not to disclose such information in 
any way without prior written permission from the Sponsor. The information in this document 
cannot be used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written permission from the Sponsor. 
The Investigator must ensure that the subject’s confidentiality is maintained for documents 
submitted to Amgen. 
Subjects will be assigned a unique identifier by the Sponsor (or designee). Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.  
On the Case Report Form demographics page, in addition to the unique subject identification 
number (Section 4.4), include the age at the time of enrollment. 
For serious adverse events reported to Amgen, subjects are to be identified by their unique 
subject identification number (Section 4.4), initials (for faxed reports, in accordance with local 
laws and regulations), and age (in accordance with local laws and regulations). 

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Documents that are not submitted to Amgen (e.g., signed ICFs) are to be kept in confidence by 
the Investigator, except as described below. 
Data Quality Assurance 
The following data quality steps will be implemented: 
 All relevant subject data relating to the study will be recorded on eCRFs unless directly 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.  
 The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
 The Investigator must permit study-related monitoring, audits, IRB review, and 
regulatory agency inspections and provide direct access to source data documents.  
 The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. Predefined agreed risks, monitoring thresholds, quality 
tolerance thresholds, controls, and mitigation plans will be documented in a risk 
management register. Additional details of quality checking to be performed on the data 
may be included in a Data Management Plan.  
 A Study Monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
 Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator in accordance with 21 CFR 312.62(c) unless local 
regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor.  
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 CFR Part 11-compliant 
electronic data capture system on an eCRF in a timely fashion. 
All data generated from external sources (e.g., laboratory and bioanalytical data), and transmitted 
to the Sponsor or designee electronically, will be integrated with the subject’s eCRF data in 
accordance with the Data Management Plan. 

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An eCRF must be completed for each enrolled subject who undergoes any screening procedures, 
according to the eCRF completion instructions. The Sponsor, or Contract Research Organization 
(Fortrea), will review the supporting source documentation against the data entered into the 
eCRFs to verify the accuracy of the electronic data. The Investigator will ensure that corrections 
are made to the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The Investigator will sign and date the eCRF via the electronic data capture system’s electronic 
signature procedure. These signatures will indicate that the Investigator reviewed and approved 
the data on the eCRF, data queries, and site notifications. 
Publications 
The policy for publication of data obtained during this study will be documented in the Clinical 
Study Agreement. 

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Appendix 7: Hepatotoxicity: Suggested Actions and Follow-up Assessments (Group 1 only) 
Subjects with normal hepatic function at Screening who experience aspartate aminotransferase 
(AST) or alanine aminotransferase (ALT) elevations  3 x upper limit of normal (ULN) or 
subjects with elevated values before drug exposure who have a 2-fold increase above baseline 
values (as specified in the Guidance for Industry Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation, July 2009) are to undergo clinical assessments and a period of “close 
observation” until abnormalities return to normal or to the subject’s baseline level as described 
below. 
 
Clinical Assessments and Observation 
Assessments that are to be performed during this period include:  
 Repeat AST, ALT, alkaline phosphatase, bilirubin (total and direct), and international 
normalized ratio (INR) within 24 hours as possible. 
 In cases of total bilirubin (TBL)  2 x ULN or INR  1.5, retesting of liver tests, bilirubin 
(total and direct), and INR is to be performed every 24 hours as possible until laboratory 
abnormalities improve. 
Testing frequency of the above laboratory tests may decrease if the abnormalities stabilize.  
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL. The 
following are to be considered depending on the clinical situation: 
 Complete blood count with differential to assess for eosinophilia 
 Serum total immunoglobulin G, anti-nuclear antibody anti-smooth muscle antibody, and 
liver kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 Serum acetaminophen (paracetamol) levels 
 A more detailed history of:  
o Prior and/or concurrent diseases or illness 
o Exposure to environmental and/or industrial chemical agents  
o Symptoms (if applicable) including right upper quadrant pain, 
hypersensitivity-type reactions, fatigue, nausea, vomiting, and fever 
o Prior and/or concurrent use of alcohol, recreational drugs, and special diets 
o Concomitant use of medications (including nonprescription medicines and herbal 
and dietary supplements), plants, and mushrooms 
 Viral serologies 
 Creatine phosphokinase, haptoglobin, lactate dehydrogenase, and peripheral blood smear 
 Appropriate liver imaging if clinically indicated 

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 Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected 
 Hepatology consult (liver biopsy may be considered in consultation with a hepatologist). 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or are considered stable by the Investigator. The 
“close observation period” is to continue for a minimum of 4 weeks after discontinuation of all 
investigational product(s) and protocol-required therapies. 
The potential drug-induced liver injury (DILI) event and additional information such as medical 
history, concomitant medications, and laboratory results must be captured in the corresponding 
electronic Case Report Form (eCRF). 
Important alternative causes for elevated AST/ALT and/or TBL values include, but are not 
limited to: 
 Hepatobiliary tract disease 
 Viral hepatitis (e.g., hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 Right-sided heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
 Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms 
 Heritable disorders causing impaired glucuronidation (e.g., Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (e.g., indinavir, 
atazanavir) 
 Alpha-one antitrypsin deficiency 
 Alcoholic hepatitis 
 Autoimmune hepatitis 
 Wilson’s disease and hemochromatosis 
 Nonalcoholic fatty liver disease including steatohepatitis 
 Non-hepatic causes (e.g., rhabdomylosis, hemolysis). 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, i.e., cases of AST or ALT  3 x ULN 
and concurrent TBL  2 x ULN or INR  1.5 (for subjects not on anticoagulation therapy) 
without evidence of alternative cause of the elevations, require the following: 

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 The event is to be reported to the Sponsor as a serious adverse event within 24 hours of 
discovery or notification of the event (i.e., before additional etiologic investigations have 
been concluded) 
 The appropriate eCRF captures information necessary to facilitate the evaluation of 
treatment-emergent liver abnormalities is to be completed and sent to the Sponsor. 
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse events if 
they meet the criteria for a serious adverse event defined in Appendix 1. 

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Appendix 8: Hepatotoxicity Stopping Rules: Suggested Actions and Follow-up Assessments 
(Group 2 only) 
Subjects with abnormal hepatic laboratory values (i.e., alkaline phosphatase [ALP], aspartate 
aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) and/or 
international normalized ratio (INR) and/or signs/symptoms of hepatitis (as described below) 
may meet the criteria for withholding or permanent discontinuation of Amgen investigational 
product or other protocol-required therapies, as specified in the Guidance for Industry 
Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009. 
Criteria for Withholding and/or Permanent Discontinuation of Amgen Investigational 
Product and Other Protocol-required Therapies Due to Potential Hepatotoxicity 
The following stopping and/or withholding rules apply to subjects for whom another cause of 
their changes in liver biomarkers (TBL, INR, and transaminases) has not been identified.  
Important alternative causes for elevated AST/ALT and/or TBL values include, but are not 
limited to: 
 Hepatobiliary tract disease 
 Viral hepatitis (e.g., hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 Right-sided heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
 Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms 
 Heritable disorders causing impaired glucuronidation (e.g., Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (e.g., indinavir, 
atazanavir) 
 Alpha-one antitrypsin deficiency 
 Alcoholic hepatitis 
 Autoimmune hepatitis 
 Wilson’s disease and hemochromatosis 
 Nonalcoholic fatty liver disease including steatohepatitis 
 Non-hepatic causes (e.g., rhabdomylosis, hemolysis). 
If investigational product(s) is/are withheld, the subject is to be followed for possible 
drug-induced liver injury (DILI) according to recommendations in the last section of this 
appendix.  

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Rechallenge may be considered if an alternative cause for impaired liver tests (ALT, AST, ALP) 
and/or elevated TBL is discovered and the laboratory abnormalities resolve to normal or baseline 
(see next section in this appendix). 
Table 3: 
Conditions for Permanent Discontinuation of Amgen Investigational Product 
and Other Protocol-required Therapies Due to Potential Hepatotoxicity 
Analyte 
Temporary Withholding  
TBL 
3x ULN at any time 
INR 
-- 
 
OR 
AST/ALT 
8x ULN at any time 
5x ULN but 8x ULN for 2 weeks 
5x ULN but 8x ULN and unable to adhere to enhanced 
monitoring schedule 
3x ULN with clinical signs or symptoms that are consistent with 
hepatitis (such as right upper quadrant pain/tenderness, fever, 
nausea, vomiting, and jaundice) 
OR 
ALP 
8x ULN at any time 
Abbreviations: ALP  alkaline phosphatase; ALT  alanine aminotransferase; AST  aspartate aminotransferase; 
INR  international normalized ratio; TBL  total bilirubin; ULN  upper limit of normal. 
 

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Table 4: 
Conditions for Withholding Amgen Investigational Product and Other 
Protocol-required Therapies Due to Potential Hepatotoxicity 
Analyte 
Permanent Discontinuation  
TBL 
2x ULN 
OR 
INR 
1.5x (for subjects not on anticoagulation therapy) 
AND 
AST/ALT 
3x ULN (when baseline was  ULN), in the presence of no 
important alternative causes for elevated AST/ALT and/or TBL 
values 
 
ALP 
-- 
Abbreviations: ALP  alkaline phosphatase; ALT  alanine aminotransferase; AST  aspartate aminotransferase; 
INR  international normalized ratio; TBL  total bilirubin; ULN  upper limit of normal. 
 
Criteria for Rechallenge of Amgen Investigational Product and Other Protocol-required 
Therapies After Potential Hepatotoxicity 
The decision to rechallenge the subject is to be discussed and agreed upon unanimously by the 
subject, Investigator, and Amgen. 
If signs or symptoms recur with rechallenge, then avacopan is to be permanently discontinued. 
Subjects who clearly meet the criteria for permanent discontinuation (as described in Table 3) are 
never to be rechallenged. 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT and 
TBL and/or INR elevation, according to the criteria specified above, require the following: 
 The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (i.e., before additional etiologic investigations 
have been concluded). 
 The appropriate electronic Case Report Form (eCRF) that captures information 
necessary to facilitate the evaluation of treatment-emergent liver abnormalities is to 
be completed and sent to Amgen. 

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Other events of hepatotoxicity and potential DILI are to be reported as serious adverse events if 
they meet the criteria for a serious adverse event defined in Appendix 1. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are withheld 
(either permanently or conditionally) due to potential DILI as specified in Table 3 and Table 4 or 
who experience AST or ALT elevations 3 x upper limit of normal (ULN) or 2-fold increases 
above baseline values for subjects with elevated values before drug are to undergo a period of 
“close observation” until abnormalities return to normal or to the subject’s baseline levels.  
Assessments that are to be performed during this period include:  
 Repeat AST, ALT, ALP, bilirubin (total and direct), and INR within 24 hours as 
possible 
 In cases of TBL 2x ULN or INR  1.5, retesting of liver tests, BIL (total and direct) 
and INR is to be performed every 24 hours as possible until laboratory abnormalities 
improve. 
Testing frequency of the above laboratory tests may decrease if the abnormalities stabilize or the 
investigational product(s) or protocol-required therapies has/have been discontinued AND the 
subject is asymptomatic. 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL.  
The following are to be considered depending on the clinical situation: 
 Complete blood count with differential to assess for eosinophilia 
 Serum total immunoglobulin G, anti-nuclear antibody anti-smooth muscle antibody, and liver 
kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 Serum acetaminophen (paracetamol) levels 
 A more detailed history of: 
o Prior and/or concurrent disease or illness 
o Exposure to environmental and/or industrial chemical agents 
o Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-
type reactions, fatigue, nausea, vomiting and fever 
o Prior and/or concurrent use of alcohol, recreational drugs, and special diets 
o Concomitant use of medications (including nonprescription medicines and herbal 
and dietary supplements), plants, and mushrooms 
 Viral serologies 

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 Creatine phosphokinase, haptoglobin, lactate dehydrogenase, and peripheral blood smear 
 Appropriate liver imaging if clinically indicated 
 Appropriate blood sampling for pharmacokinetic analysis, if this has not already been 
collected 
 Hepatology consult (liver biopsy may be considered in consultation with a hepatologist). 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the Investigator. The “close 
observation period” is to continue for a minimum of 4 weeks after discontinuation of all 
investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications, and laboratory results must be captured in the corresponding eCRFs.  
 

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Appendix 9: Schedule of Assessments 

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k The PK samples collected on Day 1 will have a sampling window of 10 minutes. Postdose samples on Day 2 will have a sampling window of 1 hour. Postdose samples Days 
3 to 8 will have a sampling window of 2 hours. Postdose samples on Days 12, 15, and 18 will have a sampling window of 4 hours. Times of all PK samples will be recorded 
to the nearest minute. Day 3, Day 5, and Day 8 PK samples will be obtained prior to start of HD. Additional plasma PK samples collected during HD on Day 1: Arterial and 
venous plasma blood samples will be collected pre-HD and at 0.5, 1, 2, and 3 hours after the start of HD and immediately following the end of HD. Venous plasma PK samples 
will also be collected at the next HD session on Day 3 (approximately 48 hours after previous one) at pre-HD, at 0.5, 1, 2, and 3 hours post the start of HD, and immediately 
following the end of HD. A sample of dialysate will be collected on Day 1 at 0.5, 1, 2, and 3 hours after the start of HD and after HD is complete for drug concentration analysis. 
The dialysate volume at 0.5, 1, 2 and 3 hours after start of dialysis (each dialysate collection time), the entire dialysate volume at the completion of the dialysis session, blood 
flow, and dialysate flow during HD will be recorded for each timepoint. The make and model of the dialyzer will be recorded. 
l Dose administration of avacopan will be given in the morning on Day 1, 4 hours prior to HD, under fed conditions. 

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f 12-lead ECGs will be collected after the subject has rested in the supine position for at least 5 minutes, and will be obtained prior to the scheduled blood draws at: Check-in; 
Day 8; and Day 18 (EOS or ET). Electrocardiograms should be collected prior to any PK corresponding timepoints. Single trace ECGs will be collected at all timepoints. 
g Vital signs measurements (seated/supine blood pressure, seated/supine pulse rate, respiratory rate, and oral body temperature) should be carried out prior to having blood drawn. 
Vital signs will be obtained at: Check-in; prior to avacopan administration and 4 hours following avacopan administration on Day 1, 24 hours postdose on Day 2, and on Days 3, 
4, 5, 6, 7, 8, and 18 (EOS or ET). Pulse rate and blood pressure will be measured using the same arm for each reading after the subject has been resting in the supine position for 
at least 5 minutes. 
h Clinical chemistry and hematology (fasted at least 8 hours). Urinalysis will not be performed for subjects in Group 2. 
i The eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation. 
  MDRD formula (mL/min/1.73m2)  175 x(serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.212 if African American) 
j Hemodialysis will be completed on Day -1 before the administration of avacopan. Hemodialysis will occur on Days 3, 5, and 7. Hemodialysis will continue as needed beyond the 
timepoints specified in the SOA. The study day, and the start and end times will be collected for all HD sessions. 
k The PK samples collected on Day 1 will have a sampling window of 10 minutes. Postdose samples on Day 2 will have a sampling window of 1 hour. Postdose samples Days 3 
to 8 will have a sampling window of 2 hours. Postdose samples on Days 12, 15, and 18 will have a sampling window of 4 hours. Times of all PK samples will be recorded to 
the nearest minute. Day 3, Day 5, and Day 7 PK samples will be obtained prior to start of HD. 
l Dose administration of avacopan will be given in the morning on Day 1 under fed conditions following HD session on Day -1.

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Appendix 10: Child-Pugh Classification of Severity of Cirrhosis 
Parameter 
Points Assigned 
1 
2 
3 
Ascites1 
Absent 
Slight or Subject on 1 
medication to control 
ascites 
Moderate or Severe 
or Subject on 2 
medications to 
control ascites 
Total bilirubin 
 2 mg/dL 
( 34.2 mol/L) 
2 – 3 mg/dL 
(34.2 – 51.3 mol/L) 
 3 mg/dL 
( 51.3 mol/L) 
Albumin 
 3.5 g/dL 
(35 g/L) 
2.8 – 3.5 g/dL 
(28 – 35 g/L) 
 2.8 g/dL 
( 28 g/L) 
Prothrombin time 
 
 
 
Seconds over control 
 4 
4 – 6  
 6 
International normalized ratio 
 1.7 
1.7 – 2.3 
 2.3 
Hepatic encephalopathy2 
None 
Grade 1 – 2  
(or suppressed with 
medication) 
Grade 3 – 4 
(refractory) 
1  Ascites is graded according to the following criteria: 
Absent: No ascites detectable by manual investigation 
Slight: Ascites palpitation doubtful 
Moderate: Ascites detectable by palpation 
Severe: Necessity of paracentesis, does not respond to medication treatment. 
2  Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles per second waves 
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2 to 3 cycles per second delta activity 
 
Modified Child-Pugh classification of the severity of liver disease according to the degree of 
ascites, the serum concentrations of total bilirubin and albumin, the prothrombin time (or 
international normalized ratio), and the degree of hepatic encephalopathy. A total score of 5 to 6 
is considered Class A (well compensated disease); 7 to 9 is Class B (significant functional 
compromise); and 10 to 15 is Class C (decompensated disease).  
 
Subjects in Group 1 will not be assessed for Child-Pugh Scores. Subjects in Group 2 with a 
Class A, B, or C Child-Pugh classification will be excluded from the study.