A Phase 1, Open-label Study to Investigate the Pharmacokinetics and Safety of Camlipixant in Male and Female Participants Aged 18-75 Years of Age With Hepatic Impairment Compared to Matched Healthy Participants With Normal Hepatic Function
Phase: PHASE1
Conditions: Cough
Sponsor: Bellus Health Inc. - a GSK company

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Clinical Study Protocol 
Primary Study 
Intervention(s) 
GSK5464714 
Other Study Intervention(s) 
Not Applicable 
Study Identifier 
221852 (Ph1 Hepatic impairment (HI) study) 
US IND Number  
142905 
Approval Date 
25 Apr 2024  
Title 
A phase 1, open-label study to investigate the 
pharmacokinetics and safety of camlipixant in male 
and female participants aged 18-75 years of age with 
hepatic impairment compared to matched healthy 
participants with normal hepatic function. 
Compound Number/Name  
GSK5464714, camlipixant 
Brief Title 
A study to investigate the pharmacokinetics and 
safety of camlipixant in male and female healthy 
participants and participants with hepatic impairment 
aged 18-75 years of age. 
Sponsor 
BELLUS Health (a wholly owned subsidiary of GSK) 
275 Armand-Frappier Blvd Laval, Quebec Canada, 
H7V 4A7. 
Sponsor signatory 
David A. Lipson, MD.  
VP Disease Area Lead, Respiratory 
Development Clinical Sciences, GSK. 
Medical monitor name and contact can be found in local study contact 
information document 
©2024 GSK group of companies or its licensor. 

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Protocol Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments, with the terms of the clinical trial agreement and with any other study 
conduct procedures and/or study conduct documents provided by GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements. 
• 
That I will comply with the terms of the site agreement. 
• 
To comply with local bio-safety legislation. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on-site or 
elsewhere without the approval of GSK and the express physical and/or digital 
informed consent of the participant. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring and data management 
processes of the study with respect to data entry and resolution of queries about the 
data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator(s)’ ownership interest 
in the sponsor or the study intervention(s), and more generally about their financial 
ties with the sponsor. GSK will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

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Study identifier 
221852 (Ph1 Hepatic impairment (HI) study) 
US IND number 
142905 
Approval date 
25 Apr 2024 
Title 
 
 
A phase 1, open-label study to investigate the 
pharmacokinetics and safety of camlipixant in male 
and female participants aged 18-75 years of age with 
hepatic impairment compared to matched healthy 
participants with normal hepatic function. 
Investigator name 
 
 
 
 
Signature 
 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
 

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Protocol Amendment Summary Of Changes Table 
DOCUMENT HISTORY 
 
Document 
Date of Issue 
Amendment 1 
25 Apr 2024 
Original Protocol 
15 December 2023 
Amendment 1 25 Apr 2024 
Overall rationale for the current Amendment:  
Protocol Amendment 1 is a substantial amendment meant for the purpose of clarification, 
 
 Other global 
changes also made to increase clarity/brevity or correct formatting errors. 
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List of main changes in the protocol and their rationale: 
 
Section # and 
title 
Description of change 
Brief rationale 
1.3 Schedule 
of Activities 
(SoA) Table 
 
9.3.3. 
Exploratory 
Endpoint 
Analysis 
 
10.2. Appendix 
2: Clinical 
laboratory tests 
5.2.1.4 
Diagnostic 
assessments 
Exclusion 
Criteria # 12 
Updated the criterion to allow for rapid 
and/or PCR testing as per local 
guidelines. 
Changed to allow some flexibility in the type of test 
required. 
5.2.3.2 Other 
exclusion 
criteria 
Exclusion 
Criteria # 22 
This criterion was not given a number 
in the original protocol and had to be 
moved to the end of the list of 
exclusions.  
Correction of a formatting issue – no change to the 
criterion 
8.4.4 AESIs 
 
8.4.5 
Regulatory 
Reporting 
Requirements 
for SAEs 
 
8.4.8 Contact 
Information for 
Reporting 
SAEs, 
Pregnancies 
and Study 
Holding Rules 
 
10.3.7 
Recording, 
assessment 
and follow-up 
of AE, SAE, 
AESIs and 
pregnancies 
 
 
The requirement to report AESIs (taste 
questionnaire results) to the sponsor 
within 24 hours was removed. The 
AESIs continue to be collected and 
monitored by the sponsor if they were 
to occur. 
 
 
The reporting requirement was removed because this 
is a single (low) dose study.   
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Section # and 
title 
Description of change 
Brief rationale 
1.1 Synopsis  
 
3. Objectives 
and Endpoints 
and/or 
Estimands 
 
Additions made to estimand text to 
better define the intentions. 
For clarity. 
10.2. Appendix 
2: Clinical 
laboratory tests 
Tests added to Table 9: HBcAb test; 
serum albumin concentration and 
indirect bilirubin 
Urine culture removed and update 
made to HBsAG timing of reflexive 
test.    
 
Changes in this section were made for clarity 
1.1 Synopsis  
 
1.3 Schedule 
of Activities 
(SoA) Table  
 
3. Objectives 
and Endpoints 
and/or 
Estimands 
 
9.3.3. 
Exploratory 
Endpoint 
Analysis 
6.8. Prior or 
concomitant 
therapy 
Timing of this investigational agent 
following any other investigational 
agent updated from 30 days to 90 
days. 
Concomitant medication statement corrected to align 
with Exclusion Criterion #9 
1.3 Schedule 
of Activities 
(SoA) Table 
 
‘Meal’ was only marked for Day 1 in 
SoA table. Days 2 -5 were also 
marked.  
Oversight 
10.1.7 
Dissemination 
of clinical study 
data  
‘Randomization codes’ removed from 
fourth bullet. 
Correction for clarity as this is an open label study. 
10.1 Appendix 
1: Regulatory, 
ethical and 
study oversight 
considerations 
 
 
10.6 Appendix 
6: Liver safety: 
suggested 
Text added throughout section. 
To align with current GSK Core Protocol Template. 
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Section # and 
title 
Description of change 
Brief rationale 
actions and 
follow-up 
assessments 
11. References 
The previous Investigator’s Brochure 
has been replaced with the current IB. 
For information. 
Global 
Correction of grammar, formatting, or 
spelling and addition of text for 
clarity/brevity 
To correct minor errors and/ or add clarifying text. 
 
 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 5 
List of main changes in the protocol and their rationale: ........................................... 6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................ 14 
1. 
PROTOCOL SUMMARY ........................................................................................ 21 
1.1. 
Synopsis ..................................................................................................... 21 
1.2. 
Schema ...................................................................................................... 24 
1.3. 
Schedule of activities (SoA) ........................................................................ 25 
2. 
INTRODUCTION .................................................................................................... 30 
2.1. 
Study rationale ............................................................................................ 30 
2.2. 
Background ................................................................................................ 30 
2.3. 
Camlipixant benefit/risk assessment ........................................................... 31 
2.3.1. 
Risk assessment .......................................................................... 31 
2.3.2. 
Benefit assessment ..................................................................... 34 
2.3.3. 
Overall benefit-risk conclusion ..................................................... 34 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS .................................................... 34 
4. 
STUDY DESIGN .................................................................................................... 35 
4.1. 
Overall design ............................................................................................. 35 
4.2. 
Scientific rationale for study design ............................................................. 38 
4.3. 
Justification for dose ................................................................................... 39 
4.4. 
End-of-study definition ................................................................................ 40 
5. 
STUDY POPULATION ........................................................................................... 40 
5.1. 
Inclusion criteria .......................................................................................... 40 
5.1.1. 
Inclusion criteria for all participants .............................................. 40 
5.2. 
Exclusion criteria ......................................................................................... 42 
5.2.1. 
Exclusion criteria for all participants ............................................. 42 
5.2.2. 
Additional exclusion criteria for hepatic impaired 
participants .................................................................................. 43 
5.2.3. 
Additional exclusion criteria for healthy control participants ......... 44 
5.3. 
Lifestyle considerations ............................................................................... 44 
5.3.1. 
Meals and dietary restrictions ...................................................... 44 
5.3.2. 
Caffeine, alcohol, and tobacco ..................................................... 44 
5.3.3. 
Activity ......................................................................................... 45 
5.4. 
Screen failures ............................................................................................ 45 
5.5. 
Criteria for temporarily delaying 
enrollment/randomization/administration of study intervention .................... 45 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 46 
6.1. 
Preparation, handling, storage, and accountability ...................................... 47 
6.2. 
Assignment to study intervention ................................................................ 47 
6.3. 
Blinding ....................................................................................................... 47 
6.4. 
Study intervention compliance .................................................................... 47 
6.5. 
Dose modification ....................................................................................... 48 
6.6. 
Continued access to study intervention after the end of the study ............... 48 

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6.7. 
Treatment of overdose ................................................................................ 48 
6.8. 
Prior and concomitant therapy .................................................................... 48 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 49 
7.1. 
Discontinuation of study intervention ........................................................... 49 
7.1.1. 
Liver chemistry stopping criteria ................................................... 50 
7.1.2. 
QTc Stopping criteria ................................................................... 52 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 52 
7.3. 
Lost to follow-up.......................................................................................... 53 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 54 
8.1. 
Administrative procedures .......................................................................... 55 
8.1.1. 
Collection of demographic data .................................................... 55 
8.1.2. 
Medical/vaccination history .......................................................... 56 
8.2. 
Efficacy and/or immunogenicity assessments ............................................. 56 
8.3. 
Safety assessments .................................................................................... 56 
8.3.1. 
Physical examination ................................................................... 56 
8.3.2. 
Vital signs .................................................................................... 56 
8.3.3. 
Electrocardiograms ...................................................................... 56 
8.3.4. 
Clinical safety laboratory tests ..................................................... 57 
8.3.5. 
Pregnancy testing ........................................................................ 57 
8.3.6. 
Study stopping rules/holding rules, safety monitoring 
AND/OR Committee .................................................................... 57 
8.4. 
Adverse Events (AEs) serious adverse events (SAEs), and other 
safety reporting ........................................................................................... 58 
8.4.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 58 
8.4.2. 
Method of detecting AEs and SAEs ............................................. 59 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 59 
8.4.4. 
AESIs .......................................................................................... 59 
8.4.5. 
Regulatory reporting requirements for SAEs ................................ 59 
8.4.6. 
Pregnancy ................................................................................... 60 
8.4.7. 
CV and death events ................................................................... 61 
8.4.8. 
Contact information for reporting SAEs, pregnancies and 
study holding rules ....................................................................... 61 
8.4.9. 
Participant card ............................................................................ 61 
8.5. 
Pharmacokinetics ....................................................................................... 61 
8.6. 
Pharmacodynamics .................................................................................... 62 
8.7. 
Genetics ..................................................................................................... 62 
8.8. 
Biomarkers ................................................................................................. 62 
8.9. 
Immunogenicity assessments ..................................................................... 62 
8.10. 
Health economics or medical resource utilization and health 
economics .................................................................................................. 63 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 63 
9.1. 
Statistical hypothesis .................................................................................. 63 
9.2. 
Analysis sets ............................................................................................... 63 
9.3. 
Statistical analyses ..................................................................................... 64 
9.3.1. 
Primary endpoints analysis .......................................................... 64 
9.3.2. 
Secondary endpoint analysis ....................................................... 65 
9.3.3. 
Exploratory Endpoint Analysis ..................................................... 66 

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9.4. 
Interim analyses .......................................................................................... 66 
9.5. 
Pre-dose sample size determination ........................................................... 66 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 67 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 67 
10.1.1. 
Regulatory and ethical considerations ......................................... 67 
10.1.2. 
Financial disclosure ..................................................................... 68 
10.1.3. 
Informed consent process ............................................................ 68 
10.1.4. 
Recruitment strategy .................................................................... 69 
10.1.5. 
Data protection ............................................................................ 69 
10.1.6. 
Committees structure ................................................................... 70 
10.1.7. 
Dissemination of Clinical Study Data ........................................... 70 
10.1.8. 
Data quality assurance ................................................................ 71 
10.1.9. 
Source documents ....................................................................... 71 
10.1.10. Study and site start and closure ................................................... 72 
10.1.11. Publication policy ......................................................................... 73 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 73 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 75 
10.3.1. 
Definition of AE ............................................................................ 75 
10.3.2. 
Definition of SAE .......................................................................... 76 
10.3.3. 
Solicited events............................................................................ 77 
10.3.4. 
Unsolicited AE ............................................................................. 78 
10.3.5. 
Definition of CV events ................................................................ 78 
10.3.6. 
Definition of TEAE ....................................................................... 78 
10.3.7. 
Recording, assessment and follow-up of AE, SAE, AESIs 
and pregnancies ............................................................................. 79 
10.4. 
Appendix 4: Contraceptive and barrier guidance ......................................... 82 
10.4.1. 
Definitions .................................................................................... 82 
10.4.2. 
Contraception guidance ............................................................... 83 
10.5. 
.................................. 84 
10.6. 
Appendix 6: Liver safety: suggested actions and follow-up 
assessments ............................................................................................... 86 
11. REFERENCES ....................................................................................................... 88 
 
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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 25 
Table 2 
Study Cohorts ........................................................................................ 36 
Table 3 
Derivation of Child-Pugh Classification Score1 ....................................... 37 
Table 4 
Determination of Encephalopathy Grade1 .............................................. 37 
Table 5 
Study Intervention (s) administered ........................................................ 46 
Table 6 
Blood Volume during the Study .............................................................. 55 
Table 7 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 60 
Table 8 
Contact information for reporting SAEs, pregnancies and study 
holding rules ........................................................................................... 61 
Table 9 
Protocol-required safety laboratory tests ................................................ 73 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 24 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation Definition 
AD 
Atopic dermatitis 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
AUC 
Area under the concentration-time curve 
BCRP 
Breast cancer resistance protein 
BID 
Twice daily 
BMI 
Body mass index 
CAR 
Chimeric antigen receptors 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL/F 
Apparent oral clearance 
 
 
 
 
Cmax 
Maximum observed concentration 
COVID-19 
Coronavirus Disease-2019 
CV% 
Coefficient of variation percentage 
CYP 
Cytochrome P450 
DDI 
Drug-drug interaction 
DMP 
Data Management Plan 
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Abbreviation Definition 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eCRF 
Electronic case report form(s) 
ex 
Extrapolation 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
FSH 
Follicle-stimulating hormone 
 
 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HI 
Hepatic impairment 
HIV 
Human immunodeficiency virus 
HRT 
Hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug 
IUD 
Intrauterine device 
LSLV 
Last subject (participant) last visit 
LSM 
Least-squares mean 
MedDRA  
Medical Dictionary for Regulatory Activities  
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Abbreviation Definition 
N 
Number 
No. 
Number 
NOAEL 
No observed adverse effect level 
OATP 
Organic anion-transporting polypeptide 
oz 
Ounce 
P-gp 
P-glycoprotein 
PBPK 
Physiologically based pharmacokinetic 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PXR 
Pregnane X receptor 
QA 
Quality Assurance 
QTcF 
Corrected value of the interval between the Q and T waves on the 
electrocardiogram tracing, corrected QT interval using Fridericia 
formula 
RCC 
Refractory chronic cough 
REC 
Research Ethics Committee 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SUSARs 
Suspected “unexpected” serious adverse reactions 
TEAE 
Treatment-emergent adverse event 
t½ 
Half-life 
Tmax 
Time of occurrence of Cmax 
ULN 
Upper limit normal 
US 
United States 

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Abbreviation Definition 
USA 
United States of America 
Vz/F 
Apparent volume of distribution 
 
 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential  
WONCBP 
Women of non-childbearing potential 
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Definition of Terms 
Term 
Definition 
Blinding 
A procedure in which 1 or more parties to the study are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
study, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a SAE. 
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned. 
Certified copy 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Co-administered 
(concomitant) products 
A product given to clinical trial participants as required 
in the protocol as part of their standard of care for a 
condition which is not the indication for which the IMP 
is being tested and is therefore not part of the objective 
of the study. 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
Investigational medicinal 
product 
A pharmaceutical form of an active substance or 
placebo being tested or used as a reference in a clinical 
trial, including products already with a marketing 
authorization but used or assembled (formulated or 
packaged) in a way different from the authorized form, 
or when used for an unauthorized indication, or when 
used to gain further information about the authorized 
form. 

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Term 
Definition 
Investigator 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team of 
individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator. 
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 
individual or party to perform those study-related duties 
and functions. 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Participant 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject. 
Pharmacogenomics 
The ICH E15 Guidance for Industry defines 
pharmacogenomics as the “Study of variation of DNA 
and RNA characteristics as related to drug or treatment 
response.” 
Pharmacogenetics, a subset of pharmacogenomics, is 
“the study of variations in DNA sequence as related to 
drug response.” Pharmacogenomic biomarkers include 
germline (host) DNA and RNA as well as somatic 
changes (e.g., mutations) that occur in cells or tissues. 
Pharmacogenomic biomarkers are not limited to human 
samples but include samples from viruses and infectious 
agents as well as animal samples. The term 
pharmacogenomic experiment includes both the 
generation of new genetic or genomic (DNA and/or 
RNA) data with subsequent analysis as well as the 
analysis of existing genetic or genomic data to 
understand drug or treatment response (PK, safety, 
efficacy or effectiveness, mode of action). 
Proteomic and metabolomic biomarker research is not 
pharmacogenomics. 

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Term 
Definition 
Primary Completion Date 
The date on which the last participant in a clinical study 
was examined or received an intervention to collect final 
data for the primary outcome measure. 
Whether the clinical study ended according to the 
protocol or was terminated does not affect this date. For 
clinical studies with more than one primary outcome 
measure with different completion dates, this term refers 
to the date on which data collection is completed for all 
the primary outcome measures. 
Source data 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Source data 
are contained in source documents (original records or 
certified copies). 
Study intervention 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Note: “Study intervention” and “study treatment” are 
used interchangeably unless otherwise specified. 
Study completion date 
The date on which the last participant in a clinical study 
was examined or received an intervention/treatment to 
collect final data for the primary outcome measures, 
secondary outcome measures, and AEs (that is, the last 
participant's last visit or LSLV). 
Study monitor 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A phase 1, open-label study to investigate the pharmacokinetics and 
safety of camlipixant in male and female participants aged 18-75 years of age with 
hepatic impairment compared to matched healthy participants with normal hepatic 
function. 
Brief Title: A study to investigate the pharmacokinetics and safety of camlipixant in 
male and female healthy participants and participants with hepatic impairment aged 
18-75 years of age. 
Rationale: 
As per the FDA hepatic guidance, a sponsor should evaluate the PK of its investigational 
drug in participants with HI when hepatic metabolism and/or excretion accounts for 
substantial portion (>20% of the absorbed drug) of the elimination of the parent or active 
metabolite. Camlipixant meets this criterion. 
Camlipixant is primarily eliminated through liver metabolism, the main routes of 
metabolism are de-alkylation, oxidation, oxidation followed by glucuronidation, 
oxidation and ring opening, and oxidation to the carboxylic acid, de-methylation. 
Camlipixant is metabolized by CYP3A4, 2C8, 1A1 and 2D6 enzymes. Total camlipixant 
AUC is predicted to increase by approximately 1.4-fold in moderate HI participants and 
by 1.6-fold in severe HI participants compared to control participants with an increase of 
up to 3-fold for the unbound AUC in the severe category. The purpose of this study is to 
determine the effect of HI on the PK profile and safety of camlipixant. The data 
generated will provide guidance on the administration of camlipixant to participants with 
impaired hepatic function. 

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Objectives, Endpoints, and Estimands: 
Objective(s) 
Endpoint(s) 
Primary 
To assess the effect of HI on the PK of camlipixant in 
participants with HI compared to healthy control 
participants. 
AUC(0-∞) and Cmax. 
Secondary 
To evaluate the safety and tolerability of camlipixant in 
participants with HI compared to healthy control 
participants. 
Incidence of Adverse Events, Serious Adverse Events 
and Adverse Events of Special Interest. 
Incidence of participants with clinically relevant changes 
in clinical laboratory tests, ECG and vital signs 
assessments. 
To assess the effect of HI on other PK parameters of 
camlipixant in participants with HI compared to healthy 
control participants. 
Tmax, t½, CL/F, and Vz/F. 
Exploratory 
Primary Estimand: 
The geometric mean of PK parameters area under the concentration-time curve from time 
zero extrapolated to infinity [AUC(0-∞)] and maximum observed plasma concentration 
[Cmax] in adult participants with HI vs. adult healthy control participants receiving 50 mg 
of camlipixant (or 25 mg in scenario 3) where issues that affect exposure to study drug 
such as emesis, dosing errors, or important protocol violations will be handled while on-
treatment strategy. The primary PK estimand is described by the following attributes: 
• 
Population: male and female adult participants 18 to 75 years of age inclusive with 
mild, moderate, or severe HI vs. healthy male and female adult participants 18 to 75 
years of age inclusive. 
• 
Treatment condition: single dose of 50 mg camlipixant or a single dose of 25 mg in 
the severe hepatic impairment group in Scenario 3. 
• 
Variable: area under the concentration-time curve from time zero extrapolated to 
infinity [AUC(0-∞)] and maximum observed plasma concentration [Cmax]. 
• 
Summary measure: ratio of the geometric mean of each HI group vs. Healthy 
matched participants for AUC(0-∞) and Cmax. 
• 
Intercurrent events: issues that affect exposure to study drug such as emesis, dosing 
errors, or important protocol violations will be handled while on-treatment strategy. 
Interest lies in estimating the effect of HI on the PK of camlipixant, when patients 
receive the single dose of camlipixant and while patients are sufficiently compliant 
with camlipixant to accurately assess exposure. 
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Overall design: 
This will be a phase 1, open-label, multi-center (3 planned), non-randomized, parallel-
group, single dose, adaptive study in adults with moderate (Part 1) and mild and/or severe 
hepatic impairment (Part 2) and matched healthy control participants with normal hepatic 
function (Part 1 and 2). All participants will undergo screening within 28 days prior to 
dosing. A decision to progress from Part 1 to Part 2 and which groups to dose on Part 2 
will be made based on the available safety and PK study results from Part 1. 
A total of up to 48 male and female participants will be enrolled. 
In Part 1, enrollment will begin for participants with moderate HI (Child-Pugh score of 7-
9; n=8). Healthy control participants (n=8) will be matched in gender, race, age (±10 
years), and weight (±20%) to participants with moderate HI. All participants will receive 
50 mg of camlipixant as a single oral dose in the fasted state. Following safety and PK 
data review by the study team of a minimum of n=6 in each group of Part 1 a decision 
will be made about which HI category to be dosed on Part 2.  
• 
Scenario 1: 
 
 
 
  
• 
Scenario 2: 
 
 
 
  
• 
Scenario 3: 
 
 
 
  
In Part 2, a single oral dose of camlipixant 50 mg (or 25 mg for severe HI in Scenario 3) 
will be administered to the selected group(s) and their matched healthy control 
participants in a fasted state. 
In both Parts, PK samples for camlipixant total plasma concentration will be collected 
pre-dose and up to 96 hours post-dose. Participants will be confined to the investigator 
site from Day -1 at the time indicated by the investigator site (at least 10 hours prior to 
Day 1 dosing), until after the 96-hour blood draw and/or study procedures. 
 
 
 
 
Number of Participants: Refer to Section 9.5. 
Data Monitoring/Other Committee: Refer to Section 10.1.6. 
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1.2. 
Schema 
Figure 1 
Study design overview 
 
 

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1.3. 
Schedule of activities (SoA) 
Table 1 
Schedule of Activities 
Procedure 
(refer to 
Section 8) 
Screening 
(up to 28 
days 
before 
Day 1) 
Study Days in Each Group 
ED 
Telephone 
Follow-up 
(14 ±2 
days post-
dose)/End 
of study 
Notes 
Days 
-28 
-1 
1 
2 
3 
4 
5 
 
 
Follow – up: Phone call 
to be conducted using 
site standard procedures 
for all participants that 
received study drug, 
including those that 
withdraw early from the 
study, to determine if 
any AE has occurred 
since the last study visit 
Allowed interval 
(Hours) 
 
C-
I 
P 
0 
0.25 
0.5 
0.75 
1 
1.5 
2 
2.5 
3 
4 
6 
8 10 12 16 
24 
36 
48 72 96 
 
 
 
Administrative procedure 
Informed 
consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 for 
details 
Inclusion and 
exclusion 
criteria 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recheck clinical status 
before 1st dose of study 
medication. 
See Section 5.1 and 
Section 5.2 for Inclusion 
and Exclusion criteria 
Demography 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.1 for 
more information 
Medical History 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substances: [Drugs, 
Alcohol, tobacco and 
caffeine. 

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Premature CV disease: 
female participant <65 
years or male participant 
<55 years in first degree 
relatives only. 
See Section 8.1.2 for 
more information. 
 
Safety Evaluation 
Full physical 
examination 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
● 
 
See Section 8.3.1 for 
more information. 
To be performed on Day 
5 or prior to early 
termination from the 
study. 
Height 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of 
Hepatic 
Function 
(Including 
Child- 
Pugh 
Classification 
[for HI 
Participants 
Only]) 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If there is a shift in score 
leading to a change of 
grade in reference to the 
screening visit, that is 
considered clinically 
significant by the PI, 
then the participant will 
be screen failed for the 
study. The participant 
may be re-screened 
later on if the hepatic 
condition stabilized. 
Vital Signs (HR, 
BP, RR and T) 
● 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
 
● 
● 
● 
● 
 
To be performed within 3 
hours prior to dosing on 
Day 1. 
See Section 8.3.2 for 
more information. 
Day 5 or prior to early 
termination from the 
study. 
12-Lead Safety 
ECG 
● 
 
● 
 
 
 
 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
● 
 
To be performed on Day 
5 or prior to early 

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termination from the 
study. 
See Section 8.3.3 for 
more information. 
Hem, Serum 
Chem, Coag, 
and UA 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
● 
 
Samples for serum 
chemistry will be 
obtained after a fast of at 
least 8 hours.  See 
section 10.2 for 
exceptions. Day 5 or 
prior to early termination 
from the study. 
Serum/Urine 
Pregnancy Test 
(Females Only) 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
● 
 
At screening, pregnancy 
test will be performed in 
serum; other pregnancy 
test can be performed in 
serum or urine as per 
local guidelines. See 
Section 8.4.6 for more 
information.. 
Day 5 or prior to early 
termination from the 
study. 
 
Serum FSH (as 
needed in 
WOCBP Only) 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug and 
Breath Alcohol 
Screen 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B 
and C 
screening] 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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AE Monitoring 
 
● 
● 
● 
Day 5 or prior to early 
termination from the 
study. 
SAE/Pregnancy 
Monitoring 
● 
● 
● 
● 
Pregnancy will be 
reported at any time 
following study drug 
administration (or up to 
30 days following 
dosing). 
Concomitant 
medications 
monitoring 
● 
● 
● 
● 
 
 
Study Intervention administration and PK assessments 
Meal 
 
● 
● 
● 
● 
● 
● 
● 
 
 
 
Camplixant 
Dosing 
 
 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants in all groups 
will be dosed at 
approximately the same 
clock time in the morning 
in a fasted state. 
Blood for 
camlipixant 
total plasma 
concentration 
 
 
● 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● ● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
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AE = Adverse event(s), BP = Blood pressure, C-I = Check-in, Chem = Chemistry, Coag = Coagulation, ConMeds = Concomitant medication, ED: Early discontinuation; ECG = 
Electrocardiogram, FSH = Follicle-stimulating hormone, F/U = Follow-up call, Hem = Hematology, HI = Hepatic impairment, HIV = Human immunodeficiency virus, HR = Heart 
rate, P = Pre-dose, PMP = Postmenopausal, RR = Respiratory rate, S = Screening, SAE = Serious adverse events, T = Temperature, UA = Urinalysis. 
● Is used to indicate a study procedure that requires databasing (either in eCRF, device, laboratory or other third party vendor). 
The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of peak 
plasma concentrations) to ensure appropriate monitoring. 
The CA and IEC will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety monitoring scheme or amendment of the ICF. The 
changes will be approved by the CA and the IEC before implementation. 
 
Other procedures 
Clinical 
Confinement  
 
● 
 
 
 
Visit 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants will be 
admitted to the site on 
Day -1, at least 10 hours 
prior to Day 1 dosing. 

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2. 
INTRODUCTION 
2.1. 
Study rationale 
The liver is involved in the clearance of many drugs through a variety of oxidative and 
conjugative metabolic pathways and/or through biliary excretion of the unbound drug or 
metabolites. Alterations of these excretory and metabolic activities by HI can lead to 
higher drug exposure. Liver disease may also alter kidney function, which can lead to 
higher drug/metabolites exposure; even in cases where the liver is not the primary route 
of elimination/excretion. Hence, hepatic disease can alter the absorption and disposition 
of drugs as well as their efficacy and safety. In accordance with the FDA hepatic 
guidance [FDA, 2003], a sponsor should evaluate the PK of its investigational drug in 
participants with HI when hepatic metabolism and/or excretion accounts for substantial 
portion (>20% of the absorbed drug) of the elimination of the parent or active metabolite. 
Camlipixant meets this criterion [IB, 2023]. 
Camlipixant is 
 
 
 
 
 
 
 [IB, 2023]. 
 
 
 
 
The purpose of this study is to determine the effect of HI on the PK profile and safety of 
camlipixant. The data generated will provide guidance on the administration of 
camlipixant to participants with impaired hepatic function. 
2.2. 
Background 
P2X3 receptors are ATP cation-gated channels located on primary afferent neurons in 
various tissues, including respiratory tract. ATP released from damaged or inflamed 
tissues acts on P2X3 receptors, triggering pain or irritation signals transmitted by sensory 
afferent fibers to the brain. Specifically, the P2X3 receptor appears to play a role in 
cough hypersensitivity and has been identified as an important target in RCC. 
Camlipixant (previously identified as BLU-5937) was shown to reduce significantly 
cough frequency in patients with baseline awake cough frequency ≥25 coughs/hour in a 
phase 2b clinical study. It is currently being investigated in phase 3 clinical trials in RCC 
patients at doses of
 and 
 mg twice daily (BID). 
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Camlipixant has been administered to healthy participants as 
 
 
 
 
 
 
 
. Two drug-drug interaction (DDI) studies have been conducted with camlipixant as 
a victim to evaluate the effect of strong inhibitors of CYP3A4 (itraconazole) and 
CYP2D6 (paroxetine) on camlipixant PK. The results showed a weak interaction between 
camlipixant and itraconazole (27% increase in AUC) and no effect of paroxetine on 
camlipixant PK. 
 
 
A detailed description of the chemistry, pharmacology, efficacy, and safety of 
camlipixant is provided in the IB and any associated IB Supplements [IB, 2023]. 
2.3. 
Camlipixant benefit/risk assessment 
Detailed information about the known and expected benefits and risks and reasonably 
expected AEs of camlipixant may be found in the IB and DSUR. 
2.3.1. 
Risk assessment 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention- camlipixant 
Ocular effects 
In long term toxicity studies in rats and dogs, camlipixant had 
non-adverse effects leading to very minor anterior cortical 
lens opacities in the lens of rats and partially reversible small, 
faint, slight to very slight, focal or multifocal corneal opacities 
in dogs. 
Exposure to camlipixant is 
limited to a single dose 
Close monitoring of AEs to 
assess ocular effects 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
No AEs related to corneal or lens lesions or other eye 
disorders suggestive of treatment-related ocular injury were 
reported in the completed Phase 1 and Phase 2 studies. 
Testicular effects 
In long term toxicity studies in rats and dogs, adverse effects 
were observed in the testis with decreased sperm in the 
epididymis which were fully reversible and demonstrated 
safety margins for the 50 mg BID dose in humans of >25-fold 
of the NOEL in rats and >6-fold of the NOAEL in dogs. No 
effect on reproductive hormone levels was seen. 
No AEs related to male reproductive disorders were reported 
in the completed Phase 1 and Phase 2 clinical trials. 
Reproductive hormone levels were tested in a subset of men 
enrolled in SOOTHE (25 males with mean age of 58.3 
years), and results showed no effects at any dose of 
camlipixant. 
Exposure to camlipixant is 
limited to a single dose. 
Close monitoring of AEs to 
assess any potential 
testicular effects. 
Cardiovascular 
effects – QT 
prolongation 
In vitro studies indicated that camlipixant is a weak inhibitor 
of hERG channels. 
Camlipixant has a dose-dependent QT prolongation effect as 
shown in a thorough QT study. The study showed the 
likelihood of a clinically relevant prolongation of QT interval 
(i.e., a ∆∆QTcF) of 10ms or more) is considered low at 
doses up to 200 mg BID. No cardiac rhythm disturbances 
(e.g., Torsade de pointes, ventricular or atrial arrythmias, 
prolonged QT interval) were reported in the completed Phase 
1 and Phase 2 clinical trials. ECG results did not suggest an 
imbalance in cardiac conduction-related abnormalities or an 
effect on QTc interval at doses up to 200 mg BID. 
Exposure to camlipixant is 
limited to a single dose and 
at a dose which a clinically 
relevant prolongation of QT 
interval is not anticipated. 
ECGs are performed at 
baseline, 1.5 hours post-
dose (at the anticipated 
time of Cmax) and at Day 5 
to monitor for any 
abnormalities. 
Close monitoring of AEs to 
assess any that may be 
secondary to QT 
prolongation. 
Hepatic effects 
Hepatocellular findings were observed with repeat dosing 
with camlipixant in mice (28-day study) and rats (26-week 
study) consistent with xenobiotic nuclear receptor CAR 
and/or PXR induction. No adverse liver findings were 
reported in the repeat-dose toxicity studies in dogs. 
In clinical studies, reversible elevations of ALT and AST 
>3×ULN not associated with concurrent increase in bilirubin 
have been observed in participants receiving higher doses of 
camlipixant (≥200 mg BID). Mild hyperbilirubinemia was also 
observed at higher doses of camlipixant (≥200 mg BID). It 
was not associated with transaminase elevations and 
appears likely due to OATP inhibition. 
Exposure to camlipixant is 
limited to a single dose. 
Liver enzymes will be 
monitored during the study. 
Close monitoring of AEs to 
assess any potential 
hepatic effects. 

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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Gastrointestinal (GI) 
disturbances 
Camlipixant-related decreased motility and mucosal erosions 
were observed in repeat-dose toxicity studies in rats up to 6 
months duration and in dogs up to 9 months duration. These 
findings were reversible and demonstrated safety margins for 
the 50 mg BID dose in humans of >8-fold of the NOAEL in 
rats and >25-fold of the NOAEL in dogs. 
Mild to moderate GI dysmotility AEs have been reported in 
the completed Phase 1 and Phase 2 clinical studies; none 
caused treatment discontinuation, and no dose relationship 
was observed. No GI ulcers or bleeding was reported. 
Exposure to camlipixant is 
limited to a single dose. 
Close monitoring of AEs to 
assess any potential 
gastrointestinal 
disturbances. 
Taste disturbances  
Taste disturbance has been reported in clinical studies of 
camlipixant and other P2X3 antagonists. 
In completed Phase 1 and Phase 2 studies, most taste 
disturbances were mild to moderate in intensity, started 
within a week of the first dose, and resolved by the end of the 
study. In phase 2 studies of 4 weeks duration and doses up 
to 200 mg BID, taste disturbances were more frequent 
among participants who received camlipixant than among 
those who received placebo (4.6% vs. 0% in SOOTHE and 
15.3% vs. 2.9% in BLUEPRINT).  
Exposure to camlipixant is 
limited to a single dose. 
Close monitoring of AEs to 
assess taste disturbance. 
Study Procedures  
Venipuncture 
Participants will be required to have blood samples taken. 
Risk of bruising, and rarely infection. 
Trained personnel will 
perform venipuncture. 
Risks of ECG pad 
removal 
Some discomfort and rash may occur where the ECG pads 
are applied and subsequently removed. 
ECGs will be conducted by 
appropriately trained 
personnel and effort made 
to minimize contact time for 
application of the pads. 
 
Reproductive risks: Currently we are not fully aware of the effects of the study drug on 
unborn babies, or pregnant or breastfeeding women. In the oral study of the effects of 
camlipixant on embryo-fetal development (EFD) in rats, no test article-related effects on 
maternal survival, clinical findings, or ovarian and uterine parameters were observed at 
any camlipixant dose levels evaluated. Lower maternal and gestational mean body 
weights and reduced food consumption were observed in pregnant female rats at the 
highest dose administered. Lower fetal body weights and increased incidence of fetal tail 
abnormality and skeletal variations were observed at this highest dose. The NOAEL for 
both maternal toxicity and for developmental toxicity was considered 100 mg/kg/day. 

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2.3.2. 
Benefit assessment 
There will be no direct therapeutic benefit for participants from receipt of study drug. An 
indirect health benefit to the participants enrolled in this study are the free medical tests 
received at screening and during the study. 
2.3.3. 
Overall benefit-risk conclusion 
The dose of camlipixant administered in this study is not anticipated to induce any 
potential risk to participants participating in this study, as it is within doses assessed in 
prior clinical studies that have been demonstrated to be well tolerated at 
 
 in healthy 
volunteers. The safety monitoring practices employed by this protocol (i.e., AEs, clinical 
laboratory tests, vital sign measurements, 12-lead ECG, and physical examination) are 
adequate to protect the participants’ safety and should detect all TEAEs. 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
 
Objective(s) 
Endpoint(s) 
Primary 
To assess the effect of HI on the PK of camlipixant in 
participants with HI compared to healthy control 
participants. 
AUC(0-∞) and Cmax. 
Secondary 
To evaluate the safety and tolerability of camlipixant in 
participants with HI compared to healthy control 
participants. 
Incidence of Adverse Events, Serious Adverse Events 
and Adverse Events of Special Interest. 
Incidence of participants with clinically relevant changes 
in clinical laboratory tests, ECG and vital signs 
assessments. 
To assess the effect of HI on other PK parameters of 
camlipixant in participants with HI compared to healthy 
control participants. 
Tmax, t½, CL/F, and Vz/F. 
 
AUC(0-): Area under the concentration-time curve from 0 extrapolated to infinity, CL/F: Apparent oral clearance, 
 
 Cmax: Maximum observed concentration, HI: Hepatic impairment, PK: 
Pharmacokinetics, Tmax: Time of occurrence of Cmax, t½: Half-life, 
, Vz/F: Apparent volume of 
distribution, 
 
Primary Estimand: 
The geometric mean of PK parameters area under the concentration-time curve from time 
zero extrapolated to infinity [AUC(0-∞)] and maximum observed plasma concentration 
[Cmax] in adult participants with HI vs. adult healthy control participants receiving 50 mg 
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of camlipixant (or 25 mg in scenario 3) where issues that affect exposure to study drug 
such as emesis, dosing errors, or important protocol violations will be handled while on-
treatment strategy. The primary PK estimand is described by the following attributes: 
• 
Population: male and female adult participants 18 to 75 years of age inclusive with 
mild, moderate, or severe HI vs. healthy male and female adult participants 18 to 75 
years of age inclusive. 
• 
Treatment condition: single dose of 50 mg camlipixant or a single dose of 25 mg in 
the severe hepatic impairment group in Scenario 3. 
• 
Variable: area under the concentration-time curve from time zero extrapolated to 
infinity [AUC(0-∞)] and maximum observed plasma concentration [Cmax]. 
• 
Summary measure: ratio of the geometric mean of each HI group vs. healthy 
matched participants for AUC(0-∞) and Cmax. 
• 
Intercurrent events: issues that affect exposure to study drug such as emesis, dosing 
errors, or important protocol violations will be handled while on-treatment strategy. 
Interest lies in estimating the effect of HI on the PK of camlipixant, when patients 
receive the single dose of camlipixant and while patients are sufficiently compliant 
with camlipixant to accurately assess exposure. 
 
4. 
STUDY DESIGN 
4.1. 
Overall design 
This will be a phase 1, open-label, multi-center (3 planned), non-randomized, parallel-
group, single dose, adaptive study in adults with moderate (Part 1) and mild and/or severe 
HI (Part 2) and matched healthy control participants with normal hepatic function (Part 1 
and 2). All participants will undergo screening within 28 days prior to dosing. A decision 
to progress from Part 1 to Part 2 and which groups to dose on Part 2 will be made based 
on the available safety and PK study results from Part 1. 
A total of up to 48 male and female participants will be enrolled. 
In Part 1, enrollment will begin for participants with moderate HI (Child-Pugh score of 7-
9; n=8). Healthy control participants (n=8) will be matched in gender, race, age (±10 
years), and weight (±20%) to participants with moderate HI. All participants will receive 
50 mg of camlipixant as a single oral dose in the fasted state. Following safety and PK 
data review by the study team of a minimum of n=6 in each group of Part 1 a decision 
will be made about which HI category to be dosed on Part 2 according to the following 
criteria (see Section 9.4 for additional details). 
• 
Scenario 1: 
 
 
 
  
• 
Scenario 2: 
 
 
 
 
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• 
Scenario 3: 
 
 
 
  
In Part 2, a single oral dose of camlipixant 50 mg (or 25 mg in Scenario 3) will be 
administered to the selected group(s) and their matched healthy control participants in a 
fasted state. If the camlipixant dose is reduced to 25 mg for the severe HI participants, the 
matching healthy controls to the severe HI group will also be dosed with 25 mg. 
In both Parts, PK samples for camlipixant total plasma concentration will be collected 
pre-dose and up to 96 hours post-dose. Participants will be confined to the investigator 
site from Day -1 at the time indicated by the investigator site (at least 10 hours prior to 
Day 1 dosing), until after the 96-hour blood draw and/or study procedures. 
 
 
 
A follow-up visit will occur 14 days (±2 days) after the dose of study treatment. The 
investigator site will attempt to contact over the phone all participants who received the 
study intervention (including participants who withdrew early from the study) using their 
standard procedures 14 ± 2 days after dosing to determine if any AE has occurred since 
the last study visit. 
A participant’s total involvement with the study will be up to 6 weeks (including 
screening window). 
Table 2 
Study Cohorts 
Study Part 
Group 
Sample Size 
Treatment1 
Part 1 
1 (Moderate HI)2 
8 
Camlipixant 50 mg tablet 
2 (Matched Healthy 
Controls to Group 1)3 
8 
Part 2 
3 (Mild HI)2 
8 
4 (Severe HI)2 
8 
5 (Matched Healthy 
Controls to Groups 3 and 
4)3,4 
8 to 16 
1 All participant will receive a single 50 mg oral dose of camlipixant in a fasted state (or 25 mg for severe HI in scenario 
3). 
2. Hepatic impairment categorized by Child-Pugh classification system (see Table 3: Mild: Score 5-6; Moderate: Score 
7-9; Severe: Score 10-15) in conjunction with the specification listed in Section 5. 
3 Healthy control participants are matched to the HI participants in gender, race, age (±10 years), and weight (±20%). 
4 A healthy control participant in group 5 can be matched to both a mild HI and a severe HI participant (Scenario 2 
only). 
Child-Pugh classification of HI: 
The Child-Pugh classification will be used to categorize HI due to its widespread use and 
acceptance by regulatory agencies (including the US FDA [FDA, 2003] and the European 
Medicines Agency [EMA, 2005]). This study design is supported by FDA guidelines for 
drugs that undergo substantial hepatic metabolism and for which a dosage guideline is 
sought for participants with HI. 
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In the current study, participants with chronic, stable HI (i.e., has a diagnosis of chronic 
[≥6 months], stable (no acute episodes of illness within 30 days prior to dosing due to 
deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to 
any etiology) will be enrolled, and the Child-Pugh scale will be used to classify the 
severity of liver disease. The scale employs 5 clinical measures of liver disease listed in 
Table 3. Each clinical measure is scored 1 to 3, with 3 indicating the most severe 
condition. A composite of all 5 scores for each clinical measure is determined for each 
participant. 
Participants with composite scores of 5 to 6, 7 to 9, and 10 to 15 on this Child-Pugh scale 
are classified as having mild, moderate, and severe HI, respectively (see Table 4 and 
Table 5). 
Table 3 
Derivation of Child-Pugh Classification Score1 
Parameters 
1 point 
2 points 
3 points 
Serum albumin (g/dL) 
>3.5 
2.8 to 3.5 
<2.8 
Total serum bilirubin 
(mg/dL) 
<2.0 
2.0 to 3.0 
>3.0 
Prothrombin time (sec 
prolonged) 
or 
International normalized 
ratio 
<4.0 
 
<1.70 
4.0 to 6.0 
 
1.70 to 2.30 
>6.0 
 
>2.30 
Ascites 
Absent 
Slight or participant on 
one medication to 
control ascites 
Moderate or participant 
on medications to 
control ascites 
Hepatic encephalopathy 
grade 
(see Table 4) 
None 
Grade 1 or 2 (or 
suppressed with 
medication) 
Grade 3 or 4 (participant 
receiving medication(s) to 
prevent encephalopathy) 
1 Adapted from U.S. Department of Health and Human Services. Guidance for Industry. Pharmacokinetics in Patients 
with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling [FDA, 2003]. 
Table 4 
Determination of Encephalopathy Grade1 
Encephalopathy Grade 
Definition 
0 
Normal consciousness, personality, neurological 
examination 
1 
Restless, sleep disturbed, irritable/agitated, tremor, 
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Encephalopathy Grade 
Definition 
2 
Lethargic, time-disoriented, inappropriate, asterixis, 
ataxia 
3a 
Somnolent, stuporous, place-disoriented, hyperactive 
reflexes, rigidity 
4a 
Unrousable coma, no personality/behavior, decerebrate 
1 Adapted from U.S. Department of Health and Human Services. Guidance for Industry. Pharmacokinetics in 
Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling [FDA, 
2003]. 
a. Participants with clinically active Grade 3 or 4 encephalopathy are excluded. 
Safety will be monitored throughout the study by repeated AE assessments, vital signs, 
physical examinations, clinical laboratory tests, and ECGs. 
Discontinued participants may be replaced at the discretion of the sponsor if they were 
not discontinued due to AEs or SAEs. 
4.2. 
Scientific rationale for study design 
This study will be an open-label, single dose, parallel-group, adaptive study for 
assessment of camlipixant in participants with HI and matched control participants. The 
study design is consistent with the recommendations outlined in the FDA guidance, 
[FDA, 2003] and the European Medicines Agency [EMA, 2005]. 
This study will be open-label as the primary endpoint is PK. 
A single dose of camlipixant will be used in this study as camlipixant PK is linear and 
time independent. 
Part 1 of the study will be conducted in participants with moderate HI and matched 
healthy controls. The adaptive design of this study allows for review of the moderate HI 
(group 1) PK and safety data before dosing mild and/or severe HI participants (groups 3 
and 4) depending on the extent of change in camlipixant AUC(0-∞) in the moderate HI 
participants (group 1) relative to matched healthy controls (group 2) (see Section 9.4). 
The adaptive nature of the study will allow reviewing dosing the severe HI group if the 
increase in exposure in the moderate group is significantly higher than predicted. 
 
 
 although a 
50 mg dose in the severe group may still be within the safety margins, a dose reduction to 
25 mg may be considered as it could be more informative to generate PK data at a dose 
less likely to approach the saturation of the liver capacity. At the same time, the adaptive 
nature of the study will avoid dosing the mild HI group if a minimum effect is observed 
in 
 
 
 vs healthy controls has been set as the limit for which camlipixant PK is 
considered not affected by moderate HI impairment as such difference would be unlikely 
to warrant a dose adjustment.  
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Cmax is not included in the decision criteria to move from Part 1 to Part 2 as HI is 
expected to affect the clearance of camlipixant and therefore mainly the AUC. Based on 
the camlipixant PK characteristics, any effect of HI on Cmax is expected to be of lower 
magnitude than an effect of HI on AUC. 
To ensure participants in the healthy control group are comparable (by gender, age, race 
and body weight) to the hepatically impaired group, each participant with HI (Group 1 
and Groups 3 and 4)) will be matched to a healthy control participant (Groups 2 and 5). 
Healthy participants will be matched to participants with different degrees of HI by age 
(± 10 years), race, body weight (±20%), and gender (1:1). 
 
 
 
; therefore, light 
smokers may be enrolled in this study as no significant impact on the PK of camlipixant 
is anticipated. 
Camlipixant plasma protein binding 
 [IB, 2023]. 
 
 
 
 
 
 
 
 
4.3. 
Justification for dose 
Camlipixant was well tolerated at 
 
 in healthy participants, and expected exposures in 
this study are lower than exposures from the highest single dose in the single ascending 
dose/multiple ascending dose and exposures in the 28-day phase 2 studies. The 
anticipated therapeutic oral doses of camlipixant of 
 and 
 BID are being 
investigated in phase 3 clinical trials in RCC participants. Camlipixant PK is relatively 
linear across the dose range being evaluated in the phase 3 studies. Therefore, a single 
dose of 50 mg camlipixant was selected for this study 
 
. 
 
 
 
 
 
 
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4.4. 
End-of-study definition 
A participant is considered to have completed the study if the participant has completed 
the study including the last contact or the last scheduled procedure shown in the SoA 
(Section 1.3). 
The end of the study is defined as the date of the last contact with the last participant. 
Following an unresolved AE/SAE to resolution or ongoing concomitant medication, or an 
unscheduled assessment that occurs after the last scheduled assessment, is considered last 
contact. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
Participants who do not qualify based on a reversible medical condition or mild 
intercurrent illness may be re-evaluated after further testing/examination or re-screened 
after the condition is resolved following discussion with the sponsor. Screening tests may 
be repeated per discretion of the PI or the sponsor. 
5.1. 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
5.1.1. 
Inclusion criteria for all participants 
1. Adult male or female participant, ≥ 18 years and ≤ 75 years of age at the screening 
visit. 
2. Male and female participants must follow protocol-specified contraception guidance 
as described in Section 10.4. 
• 
Female Participants: A female participant is eligible to participate if she is not 
pregnant or breastfeeding, and one of the following conditions applies: 
− 
Is a woman of non-childbearing potential (WONCBP) as defined in Section 
10.4: Contraceptive and Barrier Guidance. 
OR 
− 
Is a WOCBP and using a contraceptive method that is highly effective, with a 
failure rate of <1%, as described in Section 10.4 during the study intervention 
period and for at least 14 days after the last dose of study intervention. The 
investigator should evaluate potential for contraceptive method failure (e.g., 
noncompliance, recently initiated) in relationship to the first dose of study 
intervention. 

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• 
A WOCBP must have a negative highly sensitive pregnancy test urine or serum as 
required by local regulations) within specify timeframe before the first dose of study 
intervention. See Section 8.3.5 Pregnancy Testing. 
− 
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the participant must be excluded 
from participation if the serum pregnancy result is positive. 
• 
Additional requirements for pregnancy testing during and after study intervention are 
located in Section 8.3.5. 
• 
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
3. Must weigh at least 50 kg and have a BMI ≥ 18.0 and ≤ 40.0 kg/m2, at the screening 
visit. 
4. Continuous non-smoker who has not used nicotine- and tobacco-containing products 
or light smoker (≤ 5 cigarettes/day or the equivalent) for the last 3 months prior to 
study screening. 
5. Understands the study procedures in the informed consent form (ICF) and is willing 
and able to comply with the protocol. 
5.1.1.1. 
Additional inclusion criteria for hepatic impaired participants 
6. Aside from HI, be sufficiently healthy for study participation based upon medical 
history, physical examination, vital signs, ECGs, and screening clinical laboratory 
profiles, as deemed by the PI or designee, including the following: 
− 
Seated blood pressure is ≥ 90/40 mmHg and ≤160/100 mmHg at the screening 
visit. 
− 
Seated heart rate is ≥40 bpm and ≤99 bpm at the screening visit. 
− 
QTcF interval is ≤480 msec and has ECG findings considered normal or not 
clinically significant by the PI or designee at the screening visit. 
− 
Estimated creatinine clearance ≥80 mL/min at the screening visit. 
− 
Total bilirubin ≤6 mg/dL. 
7. Has a score on the Child-Pugh scale at the screening visit as follows: 
− 
Severe HI: ≥10 and ≤15; or 
− 
Moderate HI: ≥7 and ≤9; or 
− 
Mild HI: ≥5 and ≤6. 
8. Has stable HI as defined by a diagnosis of chronic (≥ 6 months), stable (no acute 
episodes of illness within 30 days prior to dosing due to deterioration in hepatic 
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5.1.1.2. 
Additional inclusion criteria for healthy control participants 
9. Medically healthy with no clinically significant medical history, physical 
examination, screening clinical laboratory profiles, vital signs and ECGs, as deemed 
by the PI or designee, including the following: 
− 
Seated blood pressure is ≥90/40 mmHg and ≤140/90 mmHg at the screening 
visit. 
− 
Seated heart rate is ≥40 bpm and ≤99 bpm at the screening visit. 
− 
QTcF interval is ≤450 msec and has ECG findings considered normal or not 
clinically significant by the PI or designee at the screening visit. 
− 
QTc ≤480 msec in participants with bundle branch block 
NOTE: 
− The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF). It is either machine-read or manually over-read. 
− AST, ALT, direct bilirubin, indirect bilirubin, and total bilirubin within normal 
ranges at the screening visit and check-in. Only abnormal values up to 1.5 x upper 
limit of normal may be repeated once. 
5.2. 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
5.2.1. 
Exclusion criteria for all participants 
5.2.1.1. 
Medical conditions 
1. Mentally or legally incapacitated or has significant emotional problems at the time of 
the screening visit or are expected during the conduct of the study. 
2. Surgical or medical condition which might significantly alter the absorption, 
distribution, metabolism, or excretion of drugs, or which may jeopardize the 
participant's safety in case of participation in the study. 
3. History or presence of liver or other solid organ transplant. 
4. History of acute pancreatitis within 1 year of study entry. 
5.2.1.2. 
Prior/concomitant therapy 
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or 
related compounds. 
6. Has received any COVID-19 vaccine within 14 days prior to dosing. 
7. Unable to refrain from or anticipates the use of prohibited prescription or non-
prescription medication, herbal remedies, or supplements as listed in Section 6.8. 

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8. History or presence of drug abuse within the past 6 months prior to dosing. Positive 
drug screen due to prescription drug use in hepatic impaired participants will be 
allowed if approved by PI on a case by case basis. 
5.2.1.3. 
Prior/concurrent clinical study experience 
9. Participation in another clinical study within 30 days (or 5 half-lives, whichever is 
longer) prior to dosing. The 30-day window will be derived from the date of the last 
blood collection or dosing, whichever is later, in the previous study to Day 1 of the 
current study. 
5.2.1.4. 
Diagnostic assessments 
10. Positive pre-study drug/alcohol screen, including THC (tetrahydrocannabinol) at the 
screening visit or at check-in, unless the positive drug test is due to prescription drug 
use that is approved by the PI or designee and sponsor. 
11. Positive results for HIV. 
12. Has positive coronavirus (SARS-CoV-2) rapid test and/or positive polymerase chain 
reaction test (based on local procedures) at check-in. 
13. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody 
(HBcAb) at screening or within 3 months prior to first dose of study intervention. 
14. Positive hepatitis C antibody test result at screening or within 3 months prior to 
starting study intervention. NOTE: Participants with positive hepatitis C antibody 
due to prior resolved disease can be enrolled, after performing a reflex test for HCV 
RNA and documenting the negative hepatitis C RNA test is obtained before the 
enrollment of participant. 
5.2.1.5. 
Other exclusion criteria 
15. Unhealthy alcohol use, defined as use more than 24 g pure alcohol per day for male 
and 12 g for female (12 g equals to approximately 300 mL beer, 100 mL wine, or 25 
mL spirits). 
16. Has been on a diet incompatible with the on study diet, in the opinion of the PI or 
designee, within the 30 days prior to dosing. 
17. Donation of blood or plasma greater than 400 ml within the last 90 days prior to 
dosing. 
18. Donation of bone marrow within the last 6 months prior to dosing. 
5.2.2. 
Additional exclusion criteria for hepatic impaired participants 
5.2.2.1. 
Medical conditions 
19. History or presence of clinically significant medical or psychiatric condition or 
disease (aside from HI) in the opinion of the PI or designee and Sponsor medical 
representative. 

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5.2.3. 
Additional exclusion criteria for healthy control participants 
5.2.3.1. 
Medical conditions 
20. History or presence of clinically significant medical or psychiatric condition or 
disease in the opinion of the PI or designee and Sponsor medical representative. 
5.2.3.2. 
Other exclusion criteria 
21. History or presence of alcoholism or drug abuse within the past 2 years prior to 
dosing. 
22. Female participant with a positive pregnancy test at the screening visit or at check-in 
or who is lactating (also applies to female HI participants). 
 
5.3. 
Lifestyle considerations 
5.3.1. 
Meals and dietary restrictions 
• 
Water (except water provided with dosing) will be restricted 1 hour prior to and 1 
hour after dosing, but will be allowed ad libitum at all other times. Other fluids may 
be given as part of meals and snacks but will be restricted at all other times 
throughout the confinement period. 
• 
Participants will be required to fast overnight for at least 10 hours prior to dosing and 
will continue the fast for at least 4 hours post-dose. 
• 
After dosing, if a participant exhibits symptom(s) of hypoglycemia, a sugary 
beverage may be provided at the discretion of the PI and must be documented. 
• 
Each meal and/or snacks served at the investigator site will be standardized and will 
be similar in caloric content and composition and will be taken at approximately the 
same time. 
• 
When confined, standard meals and snacks will be provided at appropriate times, 
except when they are required to fast. When confined in the investigator site, 
participants will be required to fast from all food and drink except water between 
meals and snacks. 
• 
Refrain from consumption of red wine, Seville oranges, grapefruit, or grapefruit 
juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices from at least 14 
days before the start of study intervention until the last PK sample collection. 
5.3.2. 
Caffeine, alcohol, and tobacco 
Participants will refrain to use the following: 
• 
During the dosing session, participants will abstain from ingesting caffeine- or 
xanthine-containing products e.g., coffee, tea, cola drinks, and chocolate for 24 hours 
before the start of dosing until after collection of the final PK sample. 

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• 
During the dosing session, participants will abstain from alcohol and alcohol 
containing foods or beverages for 48 hours before the start of dosing until after 
collection of the final PK sample. 
• 
Participants who use tobacco products will be instructed that use of nicotine-
containing products (including nicotine patches) will not be permitted while they are 
in the clinical unit. 
5.3.3. 
Activity 
Participants will remain ambulatory or seated upright for the first 4 hours after the 
morning camlipixant dosing, except when they are supine or semi-reclined for study 
procedures. However, should AEs occur at any time, participants may be placed in an 
appropriate position or will be permitted to lie down on their right side. 
• 
Participants will abstain from strenuous exercise before each blood collection for 
clinical laboratory tests. Participants may participate in light recreational activities 
during studies (e.g., watching television, reading). 
5.4. 
Screen failures 
Within 28 days prior to dosing, medical history and demographic data, including name, 
sex, age, race, ethnicity, body weight (kg), height (cm), BMI (kg/m2), and tobacco use 
(including number of cigarettes smoked per day) will be recorded. At the screening visit, 
each participant will be assessed by collection of AEs, SAEs, clinical laboratory tests, 
vital sign measurements (heart rate, blood pressure, temperature, and respiratory rate), 
12-lead ECG, and a physical examination. 
A screen failure occurs when a participant who consents to participate in the clinical 
study is not subsequently entered in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, any protocol deviations 
and any serious adverse events (SAEs). If there is a shift in score leading to a change of 
grade in reference to the screening visit, then the participant will be screen failed for the 
study. The participant may be re-screened later on if the hepatic condition stabilized. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be re-screened once. Re-screened participants should be assigned a new participant 
number are to be record in the participants’ eCRF. 
5.5. 
Criteria for temporarily delaying 
enrollment/randomization/administration of study 
intervention 
Not applicable. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
The definition of study intervention is provided in the Definition of Terms 
 
Table 5 
Study Intervention (s) administered 
Intervention Label 
BLU-5937 
Intervention Name 
Camlipixant BLU-5937 (GSK5464714) 
Intervention Description 
Camlipixant BLU-5937 (GSK5464714) 50 mg* tablet 
Type 
Drug 
Dose Formulation 
Tablet 
Unit Dose Strength(s) 
50 mg* 
Dosage Level(s) 
50 mg* single dose At 0 hour on Day 1** 
Route of Administration 
Oral*** 
Use 
Experimental 
IMP and NIMP/AxMP 
IMP 
Sourcing 
Provided centrally by the 
Sponsor. 
Packaging and Labeling 
Study intervention will be provided in a container. Each 
container contains 68 tablets and will be labeled as 
required per country requirement. 
* 25 mg tablets will be supplied if the severe HI group requires a dose reduction. 
** The exact clock time of dosing will be recorded. Hour 0 will be set as dosing time. Participants in all groups will be 
dosed at approximately the same clock time in the morning. 
*** Study drugs will be administered orally with approximately 240 mL of water. Participants will be instructed not to 
crush, split, or chew the study drug. 

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6.1. 
Preparation, handling, storage, and accountability 
• 
The investigator or designee must confirm appropriate conditions (e.g., temperature) 
have been maintained during transit for all study intervention received, and any 
discrepancies are reported and resolved before use of the study intervention. 
• 
Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. 
• 
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
• 
The investigator, institution, the head of the medical institution (where applicable), 
or authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (i.e., receipt, reconciliation, and final 
disposition records). 
• 
Further guidance and information for the final disposition of unused study 
interventions are provided in the pharmacy manual. 
• 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. 
• 
A MSDS/equivalent document describing occupational hazards and recommended 
handling precautions either will be provided to the investigator, where this is 
required by local laws, or is available upon request from GSK. 
6.2. 
Assignment to study intervention 
Each participant will be assigned a unique identification number upon the screening visit.  
Participants will receive the treatment on one occasion. 
6.3. 
Blinding 
This is an open-label study and all participants will be receiving the same 50 mg dose. 
The severe hepatic impaired group (Group 4) and the matched healthy controls (Group 5) 
may receive a reduced dose of 25 mg in Scenario 3 based on the review of safety and PK 
data in Part 1. The dose used in Group 4 and Group 5 will be communicated to the site 
prior to the start of screening.  
6.4. 
Study intervention compliance 
As participants are dosed at the site, they will receive study treatment directly from the 
investigator or designee, under medical supervision. A qualified designee will be 
responsible for monitoring the administration of the timed oral dose. The date and time of 
the dose administered in the clinic will be recorded in the source documents. 

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6.5. 
Dose modification 
The dose and administration of the study drug may be modified in the severe HI 
participants and in matching healthy controls to severe HI participants but may not be 
modified in other participants. 
6.6. 
Continued access to study intervention after the end of the 
study 
Not applicable. 
6.7. 
Treatment of overdose 
In the event of an overdose, the investigator/treating physician should: 
• 
Although unlikely to occur as study drug is administered as a single dose under 
direct supervision, should a participant experience an overdose with camlipixant 
(with or without an AE/SAE), protocol deviation will need to be documented and 
reported promptly to the sponsor. 
• 
Evaluate the participant to determine, in consultation with the medical monitor, if 
possible, whether study intervention should be interrupted or whether the dose 
should be reduced. 
• 
Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
study intervention can no longer be detected systemically (at least 5 days), as 
medically appropriate. 
6.8. 
Prior and concomitant therapy 
All participants must not have received another investigational agent within 90 days prior 
to dosing. 
For all participants, any drugs known to be moderate and strong inhibitors of 
, 
and 
, including St. John’s Wort, will be restricted for 14 days or 5 half-lives (or 5 
half-lives, whichever is longer) prior to dosing and throughout the study. For all 
participants, any drugs known to be 
 
enzymes will be restricted for 28 days (or 5 half-lives, whichever is longer) prior to 
dosing and throughout the study. Use of weak inhibitors or inducers may be deemed 
acceptable following consultation with the sponsor and the PI or designee. Appropriate 
sources (e.g., Flockhart TableTM) will be consulted to confirm lack of potential 
PK/pharmacodynamic interaction with the study drug. 
For all participants proton pump inhibitors and dabigatran will be restricted for at least 14 
days prior to dosing and throughout the study. 
Healthy participants will be restricted from using any prescription medications/products 
and any over-the-counter, non-prescription preparations (including vitamins, minerals, 
dietary supplements, and phytotherapeutic/herbal/plant derived preparations) from at 
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least 14 days (or 5 half-lives, whichever is longer) prior to dosing and throughout the 
study. Healthy participants that are on stable medication (i.e., steady dose, drug, and 
regimen) for at least 8 weeks may be enrolled upon approval by the PI (or designee) and 
sponsor (e.g., stable/well-managed hypertension and hypercholesterolemia). 
Participants with HI who are taking medications to treat manifestations of hepatic disease 
or medications needed to treat for stable diseases (e.g., diuretics such as Spironolactone, 
angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, beta-
blockers, lactulose, rifaximin or antibiotics used for spontaneous bacterial peritonitis like 
fluoroquinolones) will be allowed to participate in the study at the discretion of the PI (or 
designee) and following consultation with the sponsor. Participants must be on a stable 
dose (i.e., steady dose, drug, and regimen) for at least 8 weeks before dosing and able to 
withhold the use for at least 4 hours post-dose; phosphate binders containing aluminum, 
calcium, or lanthanum salts; iron supplements or other metal cations; H2-receptor 
antagonists; or multivitamins containing iron or zinc must be withheld at least 10 hours 
before dosing and at least 6 hours post-dose. 
Following study drug administration, paracetamol (up to 2 g per 24 hours) may be 
administered at the discretion of the PI or designee. Thyroid hormone replacement 
medication may be permitted if participant has been on same stable dose for the last 8 
weeks prior to study drug administration. Birth control methods are allowed as described 
in Section 10.4 (Appendix 4), and hormone replacement therapy may also be permitted. 
All medications taken by participants during the course of the study will be recorded. 
Concurrent medication during the course of the study including both prescription and 
non-prescription drugs may be permitted based on the timing of study drug 
administration and its pharmacology, however must first be discussed with the PI or 
designee and sponsor prior to dosing, unless appropriate medical care necessitates that 
therapy should begin before the PI or designee and sponsor can be consulted. 
If deviations occur, the PI will decide on a case-by-case basis whether the participant 
may continue participation in the study based on the time the study drug was 
administered and its pharmacology. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
As each participant receives a single dose of study intervention, later discontinuation of 
study drug is not possible. If an AE or other situation is identified, it is preferred for the 
participant to remain in the study for full evaluation per the SoA (Section 1.3). 
If the participant experiences a liver event, refer to Section 10.6 for required Liver Safety 
Actions and Follow-up Assessments; the participant does not need to be withdrawn from 
the study. 

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The primary reason for premature discontinuation of the study intervention will be 
documented in the [CRF/eCRF] based on the list below: 
Reasons 
Additional items/Sub-reasons 
Lost to follow-up 
Participant Relocated  
Participant was Incarcerated  
Other, specify 
Unknown 
Physician Decision 
Specify Safety, behavioral 
Protocol Deviation 
Specify Incorrect dose Or dose not given 
Site Terminated by Sponsor 
  
Study Terminated by Sponsor 
  
Withdrawal by Participant 
Burden of Procedure  
Participant Relocated  
COVID-19  
Other 
Unknown 
Other 
Specify 
Death 
  
7.1.1. 
Liver chemistry stopping criteria 
Discontinuation of study intervention for abnormal liver tests is required by the 
investigator when a participant meets one of the conditions outlined in the algorithm or in 
the presence of abnormal liver chemistries not meeting protocol-specified stopping rules 
if the investigator believes that it is in best interest of the participant. 
Study intervention will be discontinued for a participant if liver chemistry stopping 
criteria are met. 
Due to this being a single dose study, participants will not be discontinued from 
treatment; however, the monitoring/follow-up criteria will apply. 

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Phase 1 Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
 
Abbreviations: ALT = alanine transaminase; INR = international normalized ratio; SAE = serious adverse event; 
ULN = upper limit of normal. 
Refer to Section 10.6 (Appendix 6) for required Liver Safety Actions and Follow-up 
Assessments. 
For participants with hepatic impairment, liver function tests may be above ULN at 
baseline. Recruitment and dosing will be stopped, and a safety review will occur 
following any of the below events: 
• 
Elevation of total bilirubin or hepatic transaminases (within an 8-day window post-
dose) beyond the following thresholds: 
− ALT or AST ≥3 x ULN starting from a baseline in the reference range; 
− Increase in ALT or AST >150 U/L for males or >100 U/L for females starting 
from a baseline outside the reference range 
− A ≥2.5-fold elevation of ALP and/or gamma glutamyl transferase (GGT) relative 
to the baseline result; 
− Total bilirubin >3 x ULN, with >50% being direct; starting from a baseline in the 
reference range; 
− Increase in total bilirubin by 2.5 mg/dL starting from a baseline outside of the 
reference range; 
Note: These findings must be verified by repeated testing following initial 
observation, OR be part of an upgoing trend. 
• 
Any other event deemed by the Investigator or Sponsor to reflect potentially 
unacceptable risk to subsequent participant associated with further dosing. 

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• 
Severe TEAE or SAE related to IP. 
7.1.2. 
QTc Stopping criteria 
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment, the investigator or qualified designee will determine if 
the participant can continue the study intervention and if any change in participant 
management is needed. This review of the ECG printed at the time of collection must be 
documented. Any new clinically relevant finding should be reported as an AE. 
A participant who meets either bulleted criteria based on the average of triplicate ECG 
readings will be withdrawn from study intervention: 
For hepatic impaired and healthy participants: 
• 
QTcF >500 msec 
• 
Change from baseline of QTcF >60 msec 
For patients with underlying bundle branch block, follow the discontinuation criteria 
listed below: 
Baseline QTc with Bundle Branch Block 
Discontinuation QTc with Bundle Branch 
Block 
<450 msec 
>500 msec 
450 – 480 msec 
≥530 msec 
Due to this being a single dose study, participants will not be discontinued from 
treatment; however, the monitoring/follow-up criteria will apply. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
A participant may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons. 
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
At the time of discontinuing from the study, if possible, an ED visit should be conducted, 
as shown in the SoA (Section 1.3). See SoA (Section 1.3) for data to be collected at the 
time of study discontinuation and follow-up and for any further evaluations that need to 
be completed. 
The participant will be permanently discontinued from the study intervention and the 
study at that time. 

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All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. If the participant withdraws 
consent for disclosure of future information, the sponsor may retain and continue to use 
any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, the participant may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study 
records. 
In addition, participants may be withdrawn from the study by the PI or designee for the 
following reasons but not limited to: 
• 
AEs/SAEs 
• 
Difficulties in blood collection 
• 
Positive pregnancy test 
• 
Positive drug or alcohol test 
If a participant is discontinued prior to study completion, efforts should be made to 
perform all procedures scheduled for the end-of-treatment (i.e., Day 4) or early 
termination as outlined in the SoA (Section 1.3). 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.7.5). 
7.3. 
Lost to follow-up 
A participant will be considered lost to follow-up if the participant is unable to be 
contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, [3] 
telephone calls, and if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the Schedule of activities 
(SoA) (Section 1.3). Protocol waivers or exemptions are not allowed. 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. Participants who have signed informed 
consent but are not eligible to proceed should be recorded in the eCRF with a status 
of ‘screen failure’. 
• 
Procedures conducted as part of the participant’s routine clinical management [(e.g., 
blood count)] and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the timeframe defined in the SoA. 
The SoA (Section 1.3) summarizes the clinical procedures to be performed at each visit. 
Individual clinical procedures are described in detail below. Additional 
evaluations/testing may be deemed necessary by the PI or designee and/or the sponsor for 
reasons related to participant safety. 
For this study, the blood collection for camlipixant is the critical parameter and needs to 
be collected as close to the exact time point as possible. All other procedures should be 
completed as close to the prescribed/scheduled time as possible, but can be performed 
prior or after the prescribed/scheduled time in the following order (except for the 
screening visit and check-in): ECGs, vital signs, PK sampling, and other procedures. 
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 

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Blood Volume drawn for study assessment: 
Table 6 
Blood Volume during the Study 
Sample Type 
Number of 
Time 
Points 
Approximate 
Volume per Time 
Point * (mL) 
Approximate 
Sample 
Volume Over 
Course 
of Study (mL) 
Screening laboratory 
safety tests 
(including 
hematology, serum 
chemistry, 
coagulation, and 
serology), FSH (for 
postmenopausal 
female participants 
only), and serum 
pregnancy (for female 
participants only). 
1 
16 
16 
On study hematology, 
serum chemistry, 
and coagulation (this 
includes serum 
pregnancy for female 
participants only 
when scheduled at 
the same time) 
2 
16 
32 
Blood for camlipixant 
PK 
20 
2 
40 
Total Blood Volume (mL)→ 
* Represents the largest collection tube that is expected to be used (a smaller tube may be used). 
** If additional safety or PK analysis are necessary, additional blood may be obtained (up to a maximum of 50 mL). 
8.1. 
Administrative procedures 
8.1.1. 
Collection of demographic data 
Record demographic data such as date of birth, sex, race, and ethnicity in the 
participant’s eCRF. 
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the trial participants, and to determine if the trial participants are truly representative of 
the impacted population. 
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8.1.2. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history including tobacco use (including 
number of cigarettes smoked per day) by interviewing the participant and/or review of 
the participant’s medical records. Record any pre-existing conditions, signs and/or 
symptoms present prior to the first dose of study intervention/study intervention/study 
start in the eCRF. 
8.2. 
Efficacy and/or immunogenicity assessments 
Not applicable. 
8.3. 
Safety assessments 
AEs, SAEs and other safety reporting will be captured as per GSK standard procedures 
(see Appendix 3, Section 10.3). 
Planned timepoints for all safety assessments are provided in the SoA (See Section 1.3). 
8.3.1. 
Physical examination 
A full physical examination including body weight (kg) will be performed as outlined in 
the SoA (Section 1.3). Additional physical examinations may be performed at other 
times, if deemed necessary by the PI or designee. 
8.3.2. 
Vital signs 
Single measurements of body temperature, respiratory rate, blood pressure, and heart rate 
will be measured as outlined in the SoA (Section 1.3). Additional vital signs may be 
taken at any other times, if deemed necessary by the PI or designee. 
Blood pressure and heart rate measurements will be performed with participants in a 
seated position for at least 5 minutes, except when they are supine or semi-reclined 
because of study procedures and/or AEs (e.g., nausea, dizziness) or if deemed necessary 
by the PI or designee. 
Vital signs will be measured within 3 hours prior to Day 1 dosing. When scheduled post-
dose, vital signs will be performed within approximately 15 minutes of the scheduled 
time point. 
8.3.3. 
Electrocardiograms 
Single 12-lead ECGs will be performed as outlined in the SoA (Section 1.3). Additional 
ECGs may be taken at any other times, if deemed necessary by the PI or designee. 
ECGs will be performed with participants in a supine position for at least 5 minutes. All 
ECG tracings will be reviewed by the PI or designee. 

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ECGs will be measured within 3 hours prior to Day 1 dosing. When scheduled post-dose, 
ECGs will be performed within approximately ±20 minutes of the scheduled time point. 
8.3.4. 
Clinical safety laboratory tests 
• 
See Section 10.2 for the list of clinical laboratory tests to be performed in accordance 
with lab manual and the SoA (Section 1.3). 
• 
The investigator must review the laboratory results, document this review, and 
record any clinically significant changes occurring during the study as an AE. The 
laboratory results must be retained with source documents. 
• 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 5 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
− In the absence of a diagnosis, abnormal laboratory findings assessments PI or 
designee or other abnormal results the investigator considers clinically significant 
will be recorded as an AE or SAE, if they meet the definition of an AE or SAE 
(refer to Section 10.3.1 and Section 10.3.2). 
− If clinically significant values do not return to normal/baseline within a period of 
time judged reasonable by the investigator, the etiology should be identified, and 
the sponsor notified. 
− If laboratory values from non-protocol-specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g, SAE or AE or dose 
modification), then the results must be recorded. 
8.3.5. 
Pregnancy testing 
• 
Female participants of childbearing potential must perform a urine/blood pregnancy 
test before the administration of study intervention. Pregnancy testing must be done 
even if the participant is menstruating at the time of the study visit. The study 
intervention may only be administered if the pregnancy test is negative. 
• 
Refer to Section 8.4.6 for the information on study continuation for participants who 
become pregnant during the study. 
8.3.6. 
Study stopping rules/holding rules, safety monitoring AND/OR 
Committee 
The investigator sites and/or PPD reserve the right to terminate the study in the interest of 
participant welfare. 
The sponsor reserves the right to suspend or terminate the study at any time. 
• 
Participant safety will be continuously monitored by the Medical Monitor, 
designated Safety Lead (or delegate) throughout the study. Pertinent findings and 

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conclusions are shared with the product’s SRT for review of the overall benefit- risk 
profile of the product. 
8.4. 
Adverse Events (AEs) serious adverse events (SAEs), and 
other safety reporting 
For definitions relating to safety information see Section 10.3. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE and other safety 
information and remain responsible for following up [all AEs OR AEs that are serious, 
considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study] (see Section 7). This includes events reported by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time period and frequency for collecting AE, SAE, and other 
safety information 
All SAEs will be collected from the start of study intervention until the final follow-up 
telephone call at the time points specified in the SoA (Section 1.3). 
SAEs assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to a GSK 
product (non-IMP) will be recorded from the time a participant consents to participate in 
the study. 
All AEs will be collected from the start of study intervention until the final follow-up 
telephone call at the timepoints specified in the SoA (Section 1.3). 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded as medical history/current medical conditions, not as 
AEs. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under 
no circumstance should this exceed 24 hours, as indicated in Section 10.3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
A poststudy AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
period defined in Section 8.4.1. 
Investigators are not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, after a participant has been discharged from the study, the investigator 
must record it in the medical records. If the investigator considers the event to be 

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reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2. 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
nonleading verbal questioning and/or questionnaires of the participant is the preferred 
method to inquire about AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AEs of special interest (as defined 
in Section 8.4.4)] will be followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is provided in Section 10.3.7.5. 
8.4.4. 
AESIs 
Adverse events of special interest (AESIs) are AEs of scientific interest specific to the 
drug class. AESIs for this study include the following, but not limited to: 
1. Taste disturbance (dysgeusia, hypogeusia, ageusia) 
2. Oral paraesthesia 
3. Oral hypoesthesia 
Participants will be asked to respond to a taste questionnaire, as detailed in Section 10.5 
(Appendix 5). This will only be captured if reporting of a taste disturbance AE is initiated 
spontaneously by the participant, following dosing on Day 1. This is monitored 
throughout and until the end of the study. One questionnaire per taste disturbance AE is 
to be completed by the clinical staff for inclusion in the EDC. 
8.4.5. 
Regulatory reporting requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities toward the safety of participants and the 
safety of a study intervention under clinical investigation are met. See [Section 8.4.1] 
for reporting timeframes. 
• 
For SAEs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.3.7.6. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 

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Table 7 
Timeframes for submitting SAE, pregnancy and other events reports 
to GSK 
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
Paper/electronic AEs Report 
24 hours* 
Paper/electronic AEs Report 
Pregnancies  
24 hours* 
Paper pregnancy notification 
report/electronic pregnancy 
report  
24 hours * 
Paper pregnancy follow-up 
report/electronic pregnancy 
report  
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff.  
‡ Paper AEs Report will be dated and signed by the investigator (or designee). For each SAE, the investigator(s) must 
document in the medical notes that they have reviewed the SAE and have provided an assessment of causality. 
8.4.6. 
Pregnancy 
Female participants who become pregnant after administration of the study intervention 
may continue the study at the discretion of the investigator. 
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until time period for reporting pregnancies should align with 
the time period for postintervention contraception determined in Section 5.1. 
• 
If a pregnancy is reported at any time following study drug administration (or up to 
30 days following dosing), the investigator will record pregnancy information on the 
Pregnancy Notification Form and submit it to the sponsor within 24 hours of learning 
of the female participant pregnancy. 
• 
Any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to the sponsor. See Table 7 for reporting 
timeframes. 
• 
Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.4.4. While the investigator is not obligated to actively seek this information 
in former study participants he or she may learn of an SAE through spontaneous 
reporting. 
• 
Any female participant who becomes pregnant while participating in the study can 
continue on the study. 

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8.4.7. 
CV and death events 
For any CV events detailed in Section 10.3 (Appendix 3) and all deaths, whether or not 
they are considered SAEs, specific CV and death sections of the eCRF will be required to 
be completed. These sections include questions regarding CV (including sudden cardiac 
death) and non-CV death. 
The CV eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms. The CV information should be recorded in the specific CV section of the eCRF 
within one week of receipt of a CV event data query prompting its completion. 
The death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
8.4.8. 
Contact information for reporting SAEs, pregnancies and study 
holding rules 
Table 8 
Contact information for reporting SAEs, pregnancies and study 
holding rules 
Study contact for questions regarding SAEs, AESIs, and pregnancies  
Contact GSK’s local and/or medical contacts 
Contacts for reporting SAEs and pregnancies  
Available 24/24 hours and 7/7 days 
uk.gsk-rd-gcsp-ctsm-admin@gsk.com 
8.4.9. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending 
physician/LAR/caregiver/family member that the participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator(s) or their back up. 
8.5. 
Pharmacokinetics 
• 
Blood samples of approximately 2 mL will be collected for measurement of total 
plasma concentrations of camlipixant as specified in the SoA (Section 1.3). 
 
 
 
 
 
 
 
 
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• 
 
 
 
 
 
 
 
• 
A maximum of 3 blood samples may be collected at additional timepoints during the 
study if warranted and agreed upon between the investigator and the sponsor. The 
timing of sampling may be altered during the course of the study based on newly 
available data (e.g., to fully characterize the elimination phase) to ensure appropriate 
monitoring. 
• 
Instructions for the collection and handling of biological samples will be provided by 
the sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• 
Samples will be used to evaluate the PK of camlipixant. Each plasma
 sample 
will be divided into 2 aliquots (1 each for PK analyses, and a backup]). Samples 
collected for analyses of camlipixant plasma concentration may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the 
study. 
• 
Genetic analyses will not be performed on these plasma samples unless consent for 
this was included in the informed consent. Participant confidentiality will be 
maintained. At visits during which [plasma/serum/whole blood/etc.] samples for the 
determination of plasma concentration of camlipixant will be taken, one sample of 
sufficient volume can be used. 
8.6. 
Pharmacodynamics 
Not applicable. 
8.7. 
Genetics 
Not applicable. 
8.8. 
Biomarkers 
Not applicable. 
8.9. 
Immunogenicity assessments 
Not applicable. 
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8.10. 
Health economics or medical resource utilization and health 
economics 
Not applicable. 
9. 
STATISTICAL CONSIDERATIONS 
The SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
the most important endpoints including primary and key secondary endpoints. 
9.1. 
Statistical hypothesis 
No formal hypotheses are being tested in this study. 
9.2. 
Analysis sets 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
All participants who were screened for eligibility. 
• 
Study Population 
Enrolled 
• 
All participants who entered the study (who received study 
intervention or underwent a post screening study 
procedure). 
• 
Note screening failures (who never passed screening even 
if re-screened) and participants screened but never 
enrolled into the study (Met eligibility but not needed) are 
excluded from the Enrolled analysis set as they did not 
enter the study. 
• 
Study Population 
 Assigned  
• 
All participants who were assigned to study intervention in 
the study. 
• 
Study Population 
Safety 
• 
Participants who received study intervention. 
• 
Safety 
PK 
• 
All participants in the Safety analysis set who had at least 1 
non-missing PK assessment (NQ values will be considered 
as non-missing values). 
• 
Data will be reported according to the actual study 
intervention. 
• 
PK 

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9.3. 
Statistical analyses 
9.3.1. 
Primary endpoints analysis 
9.3.1.1. 
Pharmacokinetics analysis 
Samples from all participants will be assayed even if the participants do not complete the 
study. 
PK parameters for the primary, secondary and exploratory endpoints will be calculated 
by 
 analysis in Phoenix WinNonlin. Further details will be described 
in the SAP.  
The primary PK parameters are: 
AUC(0-∞) 
The area under the concentration-time 
curve, from time 0 extrapolated to infinity 
Cmax 
Maximum observed concentration 
Descriptive statistics: 
The plasma camlipixant concentrations and the PK parameters listed above will be 
summarized using the appropriate descriptive statistics which will be fully outlined in the 
SAP. 
Analysis of variance: 
A linear model will be fitted to the log-transformed blood PK parameters (AUC0-∞, and 
Cmax) to assess the effect of HI on the PK of camlipixant. The model will constitute 
moderate HI vs. Healthy participants in Part 1.  
In the case of Scenario 1, only severe HI participants will be enrolled in Part 2. In this 
scenario, the model will constitute severe HI vs. Healthy participants in Part 2. 
In the case of Scenario 2, both mild HI and severe HI participants will be enrolled in Part 
2 at the same dose. The model then will constitute severe, mild HI vs. Healthy 
participants in Part 2. In this scenario, healthy participants in Part 2 can be matched to 
both mild and severe HI participants. The model tackles this by pooling healthy 
participants in Part 2. 
In the case of Scenario 3, healthy participants can only be matched to either a mild or 
severe HI participant in order to accommodate the two doses. In this scenario, a separate 
model will be fit for each of the severe and mild HI groups in Part 2. If severe HI 
participants are not dosed in Part 2, then a separate model will be fit only for mild HI 
participants. 
 
 
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The analyses of interest are as follows: 
• 
Moderate HI (Group 1) compared to their matched control participant (Group 2) 
• 
Mild HI (Group 3) compared to their matched control participant (Group 5) 
• 
Severe HI (Group 4) compared to their matched control participant (Group 5). Note: 
Healthy participants in Group 5 can be matched to both mild (Group-3) and severe 
(Group-4) HI participants.  
Note: In Scenario 2, healthy participants in Group 5 can be matched to both mild (Group-
3) and severe (Group-4) HI participants. In Scenario 3, healthy participants can only be 
matched to either a mild or severe HI participant. 
9.3.2. 
Secondary endpoint analysis 
Other PK parameters of interest are Tmax, t1/2, CL/F and Vz/F. If there is not sufficient 
data to analyze AUC(0-∞) with a linear model, then AUC(0-t) will be calculated and 
analyzed. 
Descriptive statistics as described in Section 9.3.1.1 will also be performed on the 
secondary PK endpoints.  
9.3.2.1. 
Safety analyses 
All safety data will be listed by participant in the final report. 
AEs will be coded using the most current version of the MedDRA available at PPD and 
summarized by treatment for the number of participants reporting the TEAE and the 
number of TEAEs reported. A by participant AE data listing including verbatim term, 
coded term, treatment, severity, and relationship to treatment will be provided.  
Secondary Endpoint: Summary of incidence of AEs, SAEs and AESIs will be provided. 
Additionally, for participants with clinically relevant changes in clinical laboratory tests, 
ECG and vital signs assessments will also be reported during the study period. Safety 
data including clinical laboratory results, vital signs assessments, and ECG will be 
summarized by time point of collection. Quantitative safety data as well as the change 
from baseline, when appropriate, will be summarized using the appropriate descriptive 
statistics. In addition, a shift table describing out of reference range shifts will be 
provided for clinical laboratory results, as appropriate. 
Concomitant medications will be listed by participant and coded using the most current 
version of WHO drug dictionary available at PPD. 
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9.4. 
Interim analyses 
An informal interim analysis of the primary endpoint will be conducted following 
completion of Part 1 of the study, with possible progression to Part 2 based on the 
following criteria: 
The SAP will describe the planned interim analyses in greater detail. 
9.5. 
Pre-dose sample size determination 
The sample size chosen for this study was selected based on FDA guidance for industry 
[FDA, 2003]. It has been determined adequate to meet the study objectives and provide 
an acceptable level of estimate precision. Eight participants will be enrolled in each HI 
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group (i.e., Groups 1, 3, and 4). Eight healthy participants will be enrolled in Group 2 and 
8 to 16 healthy participants in Group 5 will be enrolled with normal hepatic function, 
matched to the age (±10 years), weight (±20%), and sex (1:1) of a participant in Group 1, 
3, and/or 4. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1. 
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 CIOMS international ethical guidelines 
− Applicable ICH GCP guidelines 
− Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• 
Protocols and any amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
• 
The investigator will be responsible for the following, as applicable: 
− Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures 
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− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, US Code of Federal 
Regulations, 21 CFR Parts 50, 56, and 312, and all other applicable local 
regulations 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
• 
The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the participants and answer all questions 
regarding the study. 
• 
Potential participants must be informed that their participation is voluntary. They 
will be required to physically or digitally sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA 
requirements, privacy and data protection requirements, where applicable, and the 
IRB/IEC or study center. 
• 
Sample testing will be done in accordance with the recorded consent of the 
individual participant. 
• 
By default, collected samples for the study will be stored for a maximum of 20 years. 
This storage period begins when the last participant completes the last study visit. 
This timeline can be adapted based on local laws, regulations or guidelines requiring 
different timeframes or procedures. In all cases, the storage period should be aligned 
with participant’s consent. These additional requirements must be formally 
communicated to, discussed and agreed with GSK.  
• 
The medical record must include a statement that physical or digital informed 
consent was obtained before the participant was enrolled in the study and the date the 
physical or digital consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF. 
• 
Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the study. 
• 
A physical or digital copy of the ICF(s) must be provided to the participant. 
• 
Participants who are re-screened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The investigator or authorized designee will 
explain to each participant the objectives of the exploratory research. Participants will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
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In case of unexpected pregnancy, participant must be informed that personal information 
such as date of birth, sex of the baby will be collected as part of safety follow-up. 
Consent for the collection of information about the baby may be obtained from the 
participant and/or their partner as per local regulations. 
10.1.4. 
Recruitment strategy 
Participants will be identified for potential recruitment using clinical database and 
IEC/IRB-approved advertisements (e.g., newspaper, social media) prior to consenting to 
take part in this study. 
10.1.5. 
Data protection 
• 
Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred. 
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
The participant must be informed that their personal study-related data will be used 
by the sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant, that their data will be used as described in 
the informed consent. 
• 
The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 
The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure 
or access. GSK, third parties working on behalf of GSK, and/or institutions working 
with GSK for the purposes of this study are contractually bound to protect participant 
coded data. GSK will protect participant coded data and will only share it as 
described in the ICF. 
• 
GSK has a global, internal policy that requires all GSK staff and complementary 
workers to report data incidents or breaches immediately, using dedicated tools. 
Clear procedures are defined for assessing and investigating data breaches to identify 
and to take appropriate remediation steps, to contain and to mitigate any risks for 
individuals resulting from a breach, in compliance with applicable laws. 

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10.1.6. 
Committees structure 
A SRT is in place for each GSK product. It comprises of a global cross-functional team 
responsible for the ongoing assessment of benefit-risk for a product. The SRT contribute 
to the continual assessment of incoming new efficacy and safety information. 
10.1.7. 
Dissemination of Clinical Study Data 
• 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries 
prior to study start and target results summaries submission within 12 months of 
primary/ study completion date. Where external regulations require earlier 
disclosure, GSK will follow those timelines. 
• 
Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 
• 
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results, including a summary of trial results 
understandable to laypersons. The investigator is encouraged to share the plain 
language summary with the study participants, as appropriate. The full study report 
will be made available upon request, after decision on marketing authorization by 
regulatory authorities. 
• 
Where required by regulation, the names of the sponsor signatory and investigator 
signatory will be made public. 
• 
GSK will provide the investigator with the participant-level line listings for their site 
only after completion of the full statistical analysis. 
• 
GSK intends to make anonymized participant-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. Data will be shared with researchers in a non-
identifying way, and appropriate measures will be taken to protect PI; these measures 
will comply with data protection and privacy laws that apply. 
 

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10.1.8. 
Data quality assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRFs unless 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 physically or electronically signing the CRF. 
• 
Guidance on completion of eCRFs will be provided in eCRF completion guidelines. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
• 
QTLs will be predefined in the QTL Plan to identify systematic issues that can 
impact participant right, safety and/or reliability of study results. These predefined 
parameters will be monitored during the study, and important deviations from the 
QTLs and remedial actions taken will be summarized in the CSR. 
• 
Monitoring details describing strategy, including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as risk 
management and mitigation strategies and analytical risk-based monitoring, 
involvement of central reading mechanism) methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the monitoring 
plan. 
• 
The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data. 
• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for a minimum period of 15 years from the issue 
of the final CSR/ equivalent summary, or in accordance with Applicable Law, 
whichever is longer. 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. 
10.1.9. 
Source documents 
• 
For this study there will not be source data recorded directly into the eCRF (i.e., no 
prior written or electronic record of data is available). 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the eCRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must 
be explained. The investigator may need to request previous medical records or 
transfer records, depending on the study. Also, current medical records must be 
available. 

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• 
Definition of what constitutes source data and its origin can be found in e.g. source 
data acknowledgment. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• 
The sponsor or designee will perform monitoring 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 participants 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. 
10.1.10. 
Study and site start and closure 
Start of study and first act of recruitment 
The start of study and the first act of recruitment are defined as FSFV (first ICF signature 
date) at a country-level. 
Study/site termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• 
Discontinuation of further study intervention development 
For site termination: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary suspension, as specified by the applicable regulatory requirements. The 

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investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
10.1.11. 
Publication policy 
GSK seeks to publish medically or scientifically significant results in searchable peer-
reviewed scientific literature within 18 months from LSLV. We follow International 
Committee of Medical Journal Editors standards for authorship and use Good 
Publications practices to guide our publications. 
10.2. 
Appendix 2: Clinical laboratory tests 
• 
The tests detailed in Table 7 will be performed by local laboratories. 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• 
Investigators must document their review of each laboratory safety report. 
Table 9 
Protocol-required safety laboratory tests 
Laboratory Tests 
Parameters 
Hematology 
• 
Platelet count 
• 
Red blood cell (RBC) count 
• 
RBC indices 
− 
Mean corpuscular volume (MCV) 
− 
Mean corpuscular hemoglobin (MCH) 
− 
%Reticulocytes 
• 
WBC count with 
differential: 
− 
Neutrophils 
− 
Lymphocytes 
− 
Monocytes 
− 
Eosinophils 
− 
Basophils 
• 
Hemoglobin 
• 
Hematocrit 

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Laboratory Tests 
Parameters 
Serum chemistry* 
• 
Blood urea 
nitrogen 
(BUN)/Urea 
• 
Potassium 
• 
Creatinine** 
• 
Sodium 
• 
Calcium 
• 
Glucose [indicate if 
fasting or non-
fasting] 
• 
Creatine 
phosphokinase 
(CPK) 
• 
Serum Albumin 
Concentration 
• 
 
− 
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic 
transaminase (SGOT) 
− 
Alanine aminotransferase (ALT)/serum glutamic-pyruvic 
transaminase (SGPT) 
− 
Alkaline phosphatase2 
− 
Total bilirubin 
− 
Direct bilirubin 
− 
Indirect bilirubin 
− 
Total protein 
Routine urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, [bilirubin, urobilinogen, nitrite, leukocyte esterase] 
by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
− 
Epithelial cells 
− 
Red Blood cells 
− 
WBC 
− 
Casts 
− 
Crystals 
Coagulation testing • 
Prothombin Time 
• 
International normalized ratio 
• 
Activated partial thromboplastin 
CCI
CCI
CCI

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Laboratory Tests 
Parameters 
Additional tests 
• 
HIV text 
• 
HBsAg (and DNA test, as applicable) 
• 
HBcAb  
• 
HCV (and RNA test for participants with HI, as applicable) 
• 
Urine drug screen- Opiates, Amphetamines, Cocaine, Cannabinoids 
• 
Breath alcohol screen 
• 
Serum/urine pregnancy test (for females only)*** 
• 
Serum FSH (for postmenopausal females only) 
• 
SARS-CoV-2 rapid test and/or polymerase chain reaction test 
* Serum chemistry tests will be performed after at least an 8-hour fast; however, in case of dropouts or rechecks, 
participants may not have fasted for 8 hours prior to when the serum chemistry sample is taken. 
** At the screening visit, creatinine clearance will be calculated using the Cockcroft-Gault formula. 
*** At screening, pregnancy test will be performed in serum; other pregnancy test can be performed in serum or urine 
as per local guidelines. 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting 
10.3.1. 
Definition of AE 
AE definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 

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• New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• Events that occur as a result of protocol-mandated procedures (i.e. invasive 
procedures, modification of participant’s previous therapeutic regimen). 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital, admission for routine examination.). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. Pre-existing diseases 
will be recorded in the medical history section of the eCRF. 
• Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. 
Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 

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An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant. 
f. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth,  
g. Is a suspected transmission of any infectious agent via an authorized medicinal 
product 
h. Other situations: 
• 
Possible Hy’s Law case: ALT ≥3x ULN AND total bilirubin ≥2x ULN (>35% 
direct bilirubin) or INR >1.5 must be reported as SAE 
• 
Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
− Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
10.3.3. 
Solicited events 
Definition of solicited event 
• 
Solicited AEs are predefined local systemic events for which the participant is 
specifically questioned.  

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10.3.4. 
Unsolicited AE 
Definition of unsolicited AE 
• 
An unsolicited AE is an AE that was not solicited and that is communicated by a 
participant who has signed the informed consent. Unsolicited AEs include serious 
and nonserious AEs. 
• 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participants will be instructed to contact the site as soon as possible 
to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant concern. Detailed information about reported 
unsolicited AEs will be collected by qualified site personnel and documented in 
the participant’s records. 
• 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participants and by 
review of available medical records at the next visit. 
10.3.5. 
Definition of CV events 
CV definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularization 
10.3.6. 
Definition of TEAE 
TEAE Definition: 
• 
A TEAE is an event that emerges during treatment, having been absent pre-
treatment or worsens relative to the pre-treatment state. 

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10.3.7. 
Recording, assessment and follow-up of AE, SAE, AESIs and 
pregnancies 
10.3.7.1. 
AE and SAE recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the eCRF required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
10.3.7.2. 
Assessment of intensity 
The investigator will make an assessment of intensity for each AE, AESIs and SAE 
reported during the study and assign it to one of the following categories: 
• 
Mild: 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities 
of daily living. 
• 
Moderate:  
A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
• 
Severe:  
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
10.3.7.3. 
Assessment of causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/AESI. The investigator will use clinical 
judgment to determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 

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• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• 
For causality assessment, the investigator will also consult the IB and/or product 
information, for marketed products. 
• 
The investigator must review and provide an assessment of causality for each 
AE/SAE and document this in the medical notes There may be situations in which an 
SAE has occurred and the investigator has minimal information to include in the 
initial report to GSK. However, it is very important that the investigator always make 
an assessment of causality for every event before the initial transmission of the SAE 
data to GSK. 
• 
The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
10.3.7.4. 
Assessment of outcomes 
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
10.3.7.5. 
Follow-up of AEs, SAEs, AESIs, pregnancies or any other events of 
interest 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK/Sponsor with a copy of any postmortem 
findings including histopathology. 
• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 

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After the initial AE/SAE/AESI/pregnancy or any other event of interest, the investigator 
is required to proactively follow each participant at subsequent visits/contacts. All SAEs 
will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up. 
Other nonserious AEs must be followed until end of the study or until the participant is 
lost to follow-up. 
Follow-up during the study 
AEs/AESIs documented at a previous visit/contact and defined as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 
follow-up. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available postmortem findings, including 
histopathology. 
Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At the 
end of the pregnancy, whether full-term or premature, information on the status of the 
mother and child will be forwarded to GSK using the paper pregnancy follow-up 
report/electronic pregnancy report and the AE Report if applicable. Generally, the follow-
up period does not need to be longer than 6 to 8 weeks after the estimated date of 
delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, the investigator must report any SAE occurring as a result of a poststudy 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention, to GSK as described in the Section 10.3.7.7. 
10.3.7.6. 
Updating of SAE and pregnancy information after removal of write 
access to the participant’s eCRF 
When additional SAE or pregnancy information is received after write access to the 
participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be sent to the Study contact for reporting SAEs (refer to Section 
8.4.3). 
10.3.7.7. 
Reporting of SAEs and pregnancies 
SAE Reporting to GSK via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to GSK will be the electronic data 
collection tool. 

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• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see next 
section) or to the GSK by telephone. 
• 
If the site during the course of the study or poststudy becomes aware of any serious, 
nonserious AEs, pregnancy exposure, related to any GSK non-IMP they will report 
these events to GSK or to the concerned competent authority via the national 
spontaneous reporting system. These will be classified as spontaneous ICSRs. 
• 
Contacts for SAE reporting can be found in Section 8.4.8. 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Email/facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the GSK. 
• 
In rare circumstances and in the absence of email/facsimile equipment, notification 
by telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting 
timeframes. 
• 
Contacts for SAE reporting can be found in Section 8.4.8. 
10.4. 
Appendix 4: Contraceptive and barrier guidance 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of childbearing potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
Adolescents of childbearing potential: Tanner stage ≥2 (post-thelarche) irrespective of the 
occurrence of menarche or following menarche. 
From the time of menarche until becoming postmenopausal unless permanently sterile 
(see below) 

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Note: Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development and 
pubic hair growth. 
10.4.1.2. 
Woman of non-childbearing potential (WONCBP) 
Women in the following categories are considered WONCBP: 
• 
Premenarchal: Tanner stage 1 (prepubertal) 
Permanently sterile due to one of the following procedures: 
a. 
Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. 
Documented bilateral oophorectomy 
For permanently sterile individuals due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. If reproductive 
status is questionable, additional evaluation should be considered. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• 
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with more than 
one FSH measurement is required. 
• 
Females on HRT and whose menopausal status is in doubt must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment. 
10.4.2. 
Contraception guidance 
Guidance for Female Participants 
Female participants of childbearing potential must agree to one of the following methods 
of contraception: 
• 
Hysteroscopic sterilization or bilateral tubal ligation at least 6 months prior to 
dosing. 
• 
Non-hormonal releasing IUD or hormonal contraceptives (e.g., oral, IUD, vaginal 
ring, transdermal patch, depot, implantable, etc.) for at least 3 months prior to dosing 

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and with either a physical (e.g., condom, diaphragm, or other) or a chemical (e.g., 
spermicide) barrier method from the time of the screening visit. 
In addition, female participants of childbearing potential will be advised to keep the same 
birth control method for at least 30 days after dosing. 
Female participant must agree not to donate ova from dosing until at least 30 days after 
dosing. 
Guidance for male participants 
Male participants who are not vasectomized for at least 4 months prior to dosing and who 
are sexually active with a female partner of childbearing potential must be willing to use 
one of the following acceptable contraceptive methods from dosing until 90 days after 
dosing: 
• 
Simultaneous use of condom and hormonal contraceptive (e.g., oral, IUD, vaginal 
ring, patch, depot, implantable, etc.) or non-hormonal intrauterine device used for at 
least 3 months prior to dosing for the female partner 
• 
Simultaneous use of condom and a diaphragm or cervical cap with spermicide for the 
female partner. 
No restrictions are required for a vasectomized male provided his vasectomy has been 
performed 4 months or more prior to dosing. A male who has been vasectomized less 
than 4 months prior to dosing must follow the same restrictions as a non-vasectomized 
male. 
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10.6. 
Appendix 6: Liver safety: suggested actions and follow-up 
assessments 
Phase 1 liver chemistry stopping criteria have been designed to assure participant safety 
and to evaluate liver event etiology. 
Phase 1 Liver Chemistry Stopping Criteria and Required Follow-Up Assessments 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
 
ALT≥3xULN 
If ALT 3xULN AND total bilirubin1,2 2xULN (for participants with known Gilbert’s syndrome 
these criteria only apply if total bilirubin 2xULN, and direct bilirubin 2xULN and at least 
doubled from baseline value) or ALT 3xULN AND INR 1.5, report as an SAE. 
Required Actions, Monitoring and Follow-up Assessments  
Actions 
Follow-Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event form, and complete an 
SAE data collection tool if the event also meets 
the criteria for an SAE2 
• 
Perform liver event follow-up assessments as 
described in the Follow-Up Assessment column 
• 
Monitor the participant until liver chemistries 
(see MONITORING ) 
MONITORING: 
If ALT≥3xULN AND total bilirubin 2xULN or INR 
>1.5: 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
and perform liver event follow-up assessments 
within 24 hours 
• 
Monitor participant twice weekly until liver 
chemistries reduce to 3xULN for ALT, 
2xULN for total bilirubin or 1.5 for INR or 
return to or remain within baseline or normal 
limits.A specialist or hepatology consultation is 
recommended 
If ALT≥3xULN AND total bilirubin <2xULN and INR 
≤1.5: 
• 
Perform liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
and perform liver event follow-up assessments 
within 24-72 hours 
• 
Monitor participant weekly until liver 
chemistries reduce to 3xULN for ALT or 
• 
Viral hepatitis serology3. 
• 
Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G (IgG) or gamma 
globulins. 
• 
Obtain INR and recheck with each liver chemistry 
assessment until the aminotransferases values show 
downward trend. 
• 
Obtain blood sample for pharmacokinetic (PK) 
analysis, 96 hr after the dose4. 
• 
Obtain serum creatine phosphokinase (CPK), lactate 
dehydrogenase (LDH), gamma-glutamyl transferase 
(GGT), glutamate dehydrogenase (GLDH) and 
serum albumin. 
• 
Fractionate bilirubin, if total bilirubin 2xULN. 
• 
Obtain complete blood count with differential to 
assess eosinophilia. 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on the 
liver event form. 
• 
Record use of concomitant medications on the 
concomitant medications CRF page including 
acetaminophen, herbal remedies, recreational drugs 
and other over-the-counter medications. 
• 
Record alcohol use on the liver event alcohol intake 
form. 
If ALT≥3xULN AND total bilirubin 2xULN or INR >1.5 
obtain the following in addition to the assessments listed 
above: 

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Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
 
ALT≥3xULN 
If ALT 3xULN AND total bilirubin1,2 2xULN (for participants with known Gilbert’s syndrome 
these criteria only apply if total bilirubin 2xULN, and direct bilirubin 2xULN and at least 
doubled from baseline value) or ALT 3xULN AND INR 1.5, report as an SAE. 
Required Actions, Monitoring and Follow-up Assessments  
Actions 
Follow-Up Assessments 
return to or remain within baseline or normal 
limits. 
• 
Serum acetaminophen adduct assay should be 
conducted (where available to assess potential 
acetaminophen contribution to liver injury unless 
acetaminophen use is very unlikely in the preceding 
week (e.g., where the participant has been resident 
in the clinical unit throughout). 
• 
Liver imaging (ultrasound, magnetic resonance, or 
computed tomography) to evaluate liver disease; 
complete liver imaging form. 
• 
Liver biopsy may be considered and discussed with 
local specialists if available for instance: 
− 
In participants when serology raises the 
possibility of autoimmune hepatitis (AIH) 
− 
In participants when suspected DILI progresses 
or fails to resolve on withdrawal of study 
intervention 
− 
In participants with acute or chronic atypical 
presentation. 
• 
 If liver biopsy is conducted, then complete liver 
biopsy form 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation testing is 
unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.  
2. 
All events of ALT 3xULN and total bilirubin 2xULN (for participants with known Gilbert’s syndrome these criteria 
only apply if total bilirubin 2xULN, and direct bilirubin 2xULN and at least doubled from baseline value) or ALT 
3xULN and INR 1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants 
receiving anticoagulants. 
3. 
Includes: hepatitis A Immunoglobulin M (IgM) antibody; HbsAg and HBcAb; hepatitis CRNA; Cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing); hepatitis E IgM antibody and RNA PCR test. HBV DNA quantification, and HDV antibody 
should be measured if participant known to be HBsAg and/or HBcAb positive prior to onset of the liver event or 
subsequently found to be HBsAg positive on investigation following the liver event. If hepatitis delta antibody 
assay cannot be performed, it can be replaced with a PCR of hepatitis D RNA virus (where needed and if this is 
feasible). 
4. 
Record the date/time of the PK blood sample draw and the date/time of the dose of study intervention prior to pk 
blood sample draw on the CRF. If the date or time of the dose is unclear, provide the participant’s best 
approximation. If the date/time of the dose cannot be approximated OR a PK sample cannot be collected in the 
time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in the 
pharmacy manual. 

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11. 
REFERENCES 
Camlipixant. BELLUS Health. Investigators’ Brochure, IB. Edition 6.0. 10 October 
2023. 
European Medicines Agency Committee for Medicinal Products (EMA) for Human Use: 
Guideline on the Evaluation on the Pharmacokinetics of Medicinal Products in Patients 
with Impaired Hepatic Function dated February 2005. 
Food and Drug Administration, FDA. Guidance for Industry: Pharmacokinetics in 
Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on 
Dosing and Labeling. (Draft Guidance May 2003). 
Kim JH, Sherman ME, Curriero FC, et al. Expression of cytochromes P450 1A1 and 1B1 
in human lung from smokers, non-smokers, and exsmokers. Toxicol Appl Pharmacol. 
2004; 199(3): 210-9. 

Signature Page for  221852 TMF-19121244 v1.0
Signature Page for TMF-19121244 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 25-Apr-2024 15:47:22 GMT+0000
PPD