Clinical trial NCT05959447
Conditions: Cough Healthy
Sponsor: Bellus Health Inc. - a GSK company
Start date: 2023-07-26; Completion date: 2023-10-13
Enrollment: 45 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 1, 2-part, open-label, fixed-sequence study evaluating potential drug-drug interactions between gemfibrozil (part 1) or dabigatran etexilate (part 2) and camlipixant (BLU-5937) 50 mg tablet in healthy participants under fasting conditions.

Detailed description:

Arms: arm 1: Participants received a single oral dose of camlipixant 50 milligram (mg) tablet on Day 1, followed by repeat oral doses of gemfibrozil 600 mg tablet twice daily (BID), every 12 hours, (total daily dose of 1200 mg) on Days 5 to 11, with co-administration of a single oral dose of camlipixant 50 mg tablet with the gemfibrozil on Day 9. There was a washout of at least 4 days between the dose of camlipixant on Day 1 and the dose of gemfibrozil on Day 5. arm 2: Participants received single oral dose of dabigatran etexilate 150 mg capsule on Day 1, followed by repeated oral doses of camlipixant 50 mg tablet twice daily (BID) (total daily dose of 100 mg) from Days 5 to 9, with co-administration of a single oral dose of dabigatran etexilate 150 mg capsule with the morning dose of camlipixant on Day 10. There was a washout of at least 4 days between the dose of dabigatran etexilate on Day 1 and the dose of camlipixant on Day 5.
Interventions: intervention 1: Camlipixant intervention 2: Dabigatran etexilate intervention 3: Gemfibrozil
Intervention descriptions: intervention 1: Camlipixant will be administered intervention 2: Dabigatran etexilate will be administered intervention 3: Gemfibrozil will be administered.

Protocol documents:
Prot_000.pdf: 
Protocol
Study ID:  221854
Official Title of Study: A PHASE 1, 2-PART, OPEN-LABEL, 
FIXED-SEQUENCE STUDY EVALUATING POTENTIAL DRUG-
DRUG INTERACTIONS BETWEEN GEMFIBROZIL (PART 1) OR 
DABIGATRAN ETEXILATE (PART 2) AND CAMLIPIXANT 
(BLU-5937) 50 mg TABLET IN HEALTHY PARTICIPANTS UNDER 
FASTING CONDITIONS
Date of Document: 29 June 2023


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PROTOCOL 220265 
Bellus Health Study Number: BUS-P1-12 
 
A PHASE 1, 2-PART, OPEN-LABEL, FIXED-SEQUENCE STUDY EVALUATING 
POTENTIAL DRUG-DRUG INTERACTIONS BETWEEN GEMFIBROZIL (PART 1) 
OR DABIGATRAN ETEXILATE (PART 2) AND CAMLIPIXANT (BLU-5937) 50 mg 
TABLET IN HEALTHY PARTICIPANTS UNDER FASTING CONDITIONS 
 
Sponsor: 
Bellus Health 
275 Armand-Frappier Blvd. 
Laval, Quebec 
Canada, H7V 4A7 
Tel.: 450 680 4500 
 
Contract Research 
Organization: 
Protocol Version: 
Final 
Date: 
20-JUN-2023 
CONFIDENTIAL 
 
This document is strictly confidential. It was developed for Bellus Health by 
. The information in this 
document may be disclosed only to persons involved in the study, ethics committees, regulatory agencies and study 
audit personnel. This document is copyrighted in favor of 
 and cannot be reproduced, modified, or 
adapted, in part or in total, without prior written approval by 
 
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Protocol Historical File 
 
 
 
 
 
 
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Sponsor Signature Page
Bellus Health Cough Inc.
275 Armand-Frappier Blvd.
Laval, Quebec
Canada H7V 4A7
Tel.: (450) 680-4500
s:
_________________
______________________
Date
Chief Scientific Officer
Tel.: 
E-mail: 
___________________
______________________
Date
, Early Phase Development
Tel.: 
E-mail: 
______________
______________________
Date
 of Clinical Pharmacology
Tel.:
E-mail:
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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Facilities and Responsible Staff 
Clinical Research Facilities 
This study will be conducted by 
 at the following facility: 
Screening and/or visits may also be performed at the 
 facility: 
 
 
Biomedical Laboratory Facilities 
Biomedical laboratory testing will be performed by the following laboratories: 
 
 
 
 
 
 
 
 
 
 
If another biomedical laboratory is used, this will be documented and annexed to the protocol. 
 
 
 
 
 
 
 
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Institutional Review Board 
Advarra Aurora, Ontario, Canada 
372 Hollandview Trail, Suite 300 
Aurora, Ontario, Canada L4G 0A5 
Tel.: 1-905-727-7989 
 
 
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Table of Contents 
PROTOCOL HISTORICAL FILE ............................................................................................. 2 
SPONSOR SIGNATURE PAGE ................................................................................................. 3 
INVESTIGATOR SIGNATURE PAGE..................................................................................... 4 
FACILITIES AND RESPONSIBLE STAFF ............................................................................. 5 
CLINICAL RESEARCH FACILITIES.................................................................................................................................... 5 
BIOMEDICAL LABORATORY FACILITIES ......................................................................................................................... 5 
CLINICAL PHARMACOLOGY AND BIOANALYSIS ............................................................................................................. 5 
BIOANALYTICAL FACILITY ............................................................................................................................................. 5 
INSTITUTIONAL REVIEW BOARD .................................................................................................................................... 6 
TABLE OF CONTENTS ............................................................................................................. 7 
LIST OF TABLES AND FIGURES ............................................................................................ 9 
LIST OF ABBREVIATIONS .................................................................................................... 10 
SYNOPSIS OF PROTOCOL .................................................................................................... 13 
1. 
INTRODUCTION ............................................................................................................. 27 
1.1 
BACKGROUND INFORMATION............................................................................................................................ 27 
1.2 
NONCLINICAL ................................................................................................................................................... 27 
1.3 
CLINICAL .......................................................................................................................................................... 28 
1.4 
BACKGROUND INFORMATION ON GEMFIBROZIL ............................................................................................... 30 
1.5 
BACKGROUND INFORMATION ON DABIGATRAN ETEXILATE ............................................................................. 31 
1.6 
STUDY RATIONALE ........................................................................................................................................... 32 
1.7 
BENEFIT/RISK ASSESSMENT .............................................................................................................................. 35 
2. 
OBJECTIVES .................................................................................................................... 37 
3. 
ENDPOINTS ...................................................................................................................... 37 
4. 
STUDY DESIGN ............................................................................................................... 37 
5. 
STUDY POPULATION .................................................................................................... 40 
5.1 
NUMBER OF PARTICIPANTS ............................................................................................................................... 40 
5.2 
INCLUSION CRITERIA ........................................................................................................................................ 40 
5.3 
EXCLUSION CRITERIA ....................................................................................................................................... 41 
5.4 
PARTICIPANT WITHDRAWAL AND REPLACEMENT ............................................................................................. 43 
6. 
STUDY TREATMENTS .................................................................................................. 44 
6.1 
DRUG SUPPLIES AND ACCOUNTABILITY ............................................................................................................ 44 
6.2 
IDENTIFICATION OF TREATMENTS ..................................................................................................................... 44 
6.3 
RANDOMIZATION AND BLINDING ...................................................................................................................... 44 
6.4 
STUDY DRUG ADMINISTRATION ....................................................................................................................... 45 
7. 
STUDY RESTRICTIONS ................................................................................................ 46 
7.1 
CONCOMITANT MEDICATIONS .......................................................................................................................... 46 
7.2 
DRUGS, NICOTINE AND ALCOHOL ..................................................................................................................... 47 
7.3 
DIET .................................................................................................................................................................. 47 
7.4 
POSTURE AND PHYSICAL ACTIVITY .................................................................................................................. 47 
8. 
STUDY PROCEDURES ................................................................................................... 48 
8.1 
PHARMACOKINETIC ASSESSMENTS ................................................................................................................... 48 
8.2 
PHARMACOGENOMIC ASSESSMENTS ................................................................................................................. 49 


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8.3 
SAFETY AND TOLERABILITY ASSESSMENTS ...................................................................................................... 49 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ......................................................................................... 52 
8.5 
PREMATURE TERMINATION OF THE STUDY ....................................................................................................... 57 
9. 
STATISTICAL ANALYSES ............................................................................................ 57 
9.1 
ANALYSIS POPULATIONS................................................................................................................................... 57 
9.2 
PHARMACOKINETIC PARAMETERS .................................................................................................................... 58 
9.3 
PHARMACOKINETIC STATISTICAL ANALYSIS .................................................................................................... 58 
9.4 
CRITERIA FOR NO DRUG-DRUG INTERACTION FOR CAMLIPIXANT .................................................................... 59 
9.5 
SAFETY AND TOLERABILITY ANALYSIS ............................................................................................................ 60 
9.6 
PHARMACOGENOMIC EVALUATION ................................................................................................................... 60 
10. 
DATA COLLECTION ...................................................................................................... 60 
11. 
REGULATORY CONSIDERATIONS AND QUALITY ASSURANCE .................... 61 
11.1 
IEC APPROVAL OF PROTOCOL AND OTHER STUDY DOCUMENTS ...................................................................... 61 
11.2 
COMPLIANCE..................................................................................................................................................... 61 
11.3 
QUALITY ASSURANCE AND MONITORING ......................................................................................................... 61 
11.4 
CONFIDENTIALITY AND RETENTION OF STUDY RECORDS ................................................................................. 62 
12. 
REFERENCES .................................................................................................................. 63 
13. 
APPENDIX 1 ..................................................................................................................... 64 
14. 
APPENDIX 2 ..................................................................................................................... 68 
 


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List of Tables and Figures 
TABLE 1. 
SCHEDULE OF ASSESSMENTS FOR PART 1 .................................................................. 21 
TABLE 2. 
SCHEDULE OF ASSESSMENTS FOR PART 2 .................................................................. 24 
FIGURE 1. STUDY DESIGN DIAGRAM FOR PART 1 .......................................................................... 38 
FIGURE 2. STUDY DESIGN DIAGRAM FOR PART 2 .......................................................................... 39 
TABLE 3. 
TIME WINDOWS FOR PK BLOOD SAMPLES FOR PART 1 ............................................. 48 
TABLE 4. 
TIME WINDOWS FOR PK BLOOD SAMPLES FOR PART 2 ............................................. 49 
TABLE 5. 
CLINICAL LABORATORY ASSESSMENTS ..................................................................... 51 
TABLE 6. 
SEVERITY SCALE ....................................................................................................... 54 
TABLE 7. 
RELATIONSHIP CATEGORIES ...................................................................................... 54 


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List of Abbreviations 
AE 
adverse event 
AEMI 
adverse event of medical interest 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
ATP 
adenosine triphosphate 
AUC 
area under the concentration-time curve 
AUC0-inf 
area under the concentration-time curve from time zero to infinity 
(extrapolated) 
AUC0-t 
area under the concentration-time curve from time zero until the last 
observed concentration 
BCRP 
breast cancer resistance protein 
 
 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CDER 
Center for Drug Evaluation and Research 
CI 
confidence interval 
CK 
creatine kinase 
Cl/F 
apparent clearance 
Cmax 
maximal observed concentration 
COVID-19 
coronavirus 2019 
CrCl 
creatinine clearance 
CRO 
contract research organization 
CTA 
Clinical Trial Application 
CV% 
coefficient of variation 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
DMP 
data management plan 
DVT 
deep vein thrombosis 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
EFD 
embryo-fetal development 
ET 
early termination 
FDA 
Food and Drug Administration 
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FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GEM-1-O-gluc 
gemfibrozil-1-O-beta-glucuronide 
GGT 
gamma-glutamyl transferase 
GMP 
Good Manufacturing Practice 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HEENT 
head, eyes, ears, nose, and throat 
HIV 
human immunodeficiency virus 
HPMC 
hydroxypropylmethylcellulose 
IB 
Investigator’s Brochure 
IBS 
irritable bowel syndrome 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IME 
important medical event 
INR 
international normalized ratio 
Kel 
terminal elimination rate constant 
LFT 
liver function test 
Max 
maximum 
MDMA 
3,4-methylenedioxymethamphetamine 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
minimum 
MRHD 
maximum recommended human dose 
NOAEL 
no observed adverse effect level 
NOEL 
no observed effect level 
NOL 
No Objection Letter 
OATP 
organic anion transporter polypeptide 
OTC 
over-the-counter 
PBPK 
physiologically based pharmacokinetic 
PC 
pharmacokinetic concentration 
PCP 
phencyclidine 
PE 
pulmonary embolism 
PEPT1 
peptide transporter 1 


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P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PT 
prothrombin time 
 
 
QT 
QT interval 
QTcF 
Fridericia’s corrected QT interval 
RBC 
red blood cell 
RCC 
refractory and unexplained chronic cough 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis system 
SD 
standard deviation 
SOP 
standard operation procedure 
SUSAR 
suspected, unexpected, serious adverse reaction 
T½ el 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
THC 
tetrahydrocannabinol 
THR 
total hip replacement 
TKR 
total knee replacement 
Tmax 
time when the maximal concentration is observed 
 
 
UGT1A1 
UDP glucuronosyltransferase 1 A1 
ULN 
upper limit of normal 
VLDL 
very low density lipoprotein 
VTE 
venous thromboembolic events 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
WHODrug 
World Health Organization Drug 
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Synopsis of Protocol 
Project Number: 
220265 
Bellus Health study number: BUS-P1-12 
Title: 
A Phase 1, 2-Part, Open-label, Fixed-sequence Study Evaluating Potential 
Drug-Drug Interactions between Gemfibrozil (Part 1) or Dabigatran 
Etexilate (Part 2) and Camlipixant (BLU-5937) 50 mg Tablet in Healthy 
Participants under Fasting Conditions 
Investigational 
Product: 
Camlipixant (BLU-5937) 50 mg Tablet 
Study Phase and Type: 
Phase 1 – Drug-Drug Interaction (DDI) 
Objectives: 
Primary objectives: 
• 
To assess the effect of repeated oral doses of gemfibrozil, a cytochrome 
P450 (CYP) 2C8 inhibitor, on the pharmacokinetics (PK) of a single 
oral dose of camlipixant (Part 1) administered to healthy participants. 
• 
To assess the effect of repeated oral doses of camlipixant on the PK of a 
single oral dose of dabigatran etexilate, a P-glycoprotein (P-gp) 
substrate (Part 2), administered to healthy participants. 
Secondary objective: 
• 
To evaluate the safety and tolerability of camlipixant when 
administered alone and in combination with gemfibrozil or dabigatran 
etexilate to healthy participants. 
Endpoints: 
Primary endpoints: 
• 
PK parameters: AUC0-inf, AUC0-t, and Cmax of camlipixant (Part 1) and 
dabigatran (Part 2*) 
Secondary endpoints: 
• 
PK parameters: Tmax, T½ el, Residual area, Kel, Cl/F, and Vz/F of 
camlipixant (Part 1) and dabigatran (Part 2*) 
*For Part 2, both total and free dabigatran will be assayed, and their PK 
parameters generated. 
• 
Safety evaluation: 
o Adverse events (AEs), serious adverse events (SAEs), adverse 
events of medical interest (AEMIs), vital signs measurements 
(blood pressure, heart rate, respiratory rate, and oral temperature), 
12-lead electrocardiogram (ECG) recordings, physical 
examinations, and clinical laboratory test results, including 
hematology, biochemistry, coagulation, and urinalysis. 
Study Design: 
This is a single-center, 2-part, Phase 1, open-label, fixed-sequence, DDI 
study designed to compare the PK of camlipixant when administered with 


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and without gemfibrozil (Part 1) or to compare the PK of dabigatran when 
administered with and without camlipixant (Part 2) in healthy participants 
under fasting conditions. Participants will be enrolled to either Part 1 or 
Part 2. In each part, participants will receive the assigned treatment. The 
start of study conduct for Part 2 is independent from Part 1 study conduct. 
In Part 1, participants will receive a single oral dose of 1 x 50 mg 
camlipixant tablet on Day 1, followed by 72 hours of PK and safety 
assessments. Repeated oral doses of 
 mg gemfibrozil tablet will be 
administered 
 
, (total daily dose of 
mg) on Days 5 to 11, with co-administration of a single oral dose of 
1 x 50 mg camlipixant tablet with the morning dose of gemfibrozil on 
Day 9. Administration of camlipixant on Day 9 will occur 1 hour 
(± 2 minutes) after administration of gemfibrozil, followed by 72 hours of 
PK and safety assessments. 
In Part 2, participants will receive a single oral dose of 
mg 
dabigatran etexilate capsule on Day 1, followed by 72 hours of PK and 
safety assessments. Repeated oral doses of 1 x 50 mg camlipixant tablet will 
be administered on Days 5 to 10 (
 mg, 
on Days 5 to 9), with same time co-administration of a single oral dose of 
mg dabigatran etexilate capsule and the dose of camlipixant in the 
morning of Day 10. This will be followed by 72 hours of PK and safety 
assessments. 
The study will include a screening visit from Day -28 to Day -1. In each 
part of the study, eligible participants will be admitted to the clinical site on 
Day -1 and will be confined until completion of the assessments on Day 12 
(Part 1) or Day 13 (Part 2). There will be a washout period of at least 4 days 
between the first dose of camlipixant on Day 1 and the first dose of 
gemfibrozil on Day 5 (Part 1), and a washout period of at least 4 days 
between the first dose of dabigatran etexilate on Day 1 and the first dose of 
camlipixant on Day 5 (Part 2). A follow-up phone call will be performed 
7 ± 2 days after discharge (Day 19 ± 2 in Part 1 and Day 20 ± 2 in Part 2). 
Study Population: 
A total of 36 healthy participants are planned to be enrolled, with 
16 participants enrolled in Part 1 and 20 participants enrolled in Part 2. 
Participants must be males or females, ≥ 18 and ≤ 55 years of age, and 
non-smoker for enrollment in the study. 
Inclusion/Exclusion 
Criteria: 
Inclusion Criteria: 
1. Male or female, non-smoker (no use of tobacco or nicotine products 
within 3 months prior to screening), ≥18 and ≤55 years of age, with 
body mass index (BMI) >18.5 and <30.0 kg/m2 and body weight 
≥50.0 kg. 
2. Healthy as defined by: 
a. the absence of clinically significant illness and surgery within 
4 weeks prior to dosing. 
b. the absence of clinically significant history of neurological, 
endocrine, cardiovascular, respiratory, hematological, 
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immunological, psychiatric, gastrointestinal, renal, hepatic, and 
metabolic disease. 
3. Female participants of non-childbearing potential must be: 
a. post-menopausal (spontaneous amenorrhea for at least 12 months 
prior to dosing) with confirmation by documented 
follicle-stimulating hormone (FSH) levels ≥40 mIU/mL; or 
b. surgically sterile (bilateral oophorectomy, bilateral salpingectomy, 
or hysterectomy) at least 3 months prior to dosing. 
4. Females of childbearing potential who are sexually active with a 
non-sterile male partner (sterile male partners are defined as men 
vasectomized since at least 3 months) must be willing to use one of the 
following acceptable contraceptive methods throughout the study and 
for 90 days after the last study drug administration: 
a. simultaneous use of intra-uterine contraceptive device without 
hormone release system placed at least 4 weeks prior to study drug 
administration, and condom for the male partner; 
b. simultaneous use of diaphragm or cervical cap with intravaginally 
applied spermicide and male condom for the male partner, started at 
least 21 days prior to study drug administration. 
c. tubal ligation at least 3 months prior to dosing. 
5. Female participants must be willing not to donate ova for 90 days after 
the last dose. 
6. Male participants who are not vasectomized for at least 3 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 the first dose and for 90 days 
after the last dose: 
a. simultaneous use of condom and hormonal contraceptive (e.g., oral, 
patch, depot injection, implant, vaginal ring, intrauterine device) or 
non-hormonal intrauterine device used for at least 4 weeks prior to 
sexual intercourse for the female partner; 
b. simultaneous use of condom and a diaphragm or cervical cap with 
spermicide for the female partner. 
7. Male participants (including men who have had a vasectomy) with a 
pregnant partner must agree to use a condom from the first dose and for 
90 days after the last dose. 
8. Male participants must be willing not to donate sperm for 90 days after 
the last dose. 
9. Able to understand the study procedures and provide signed informed 
consent to participate in the study. 


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Exclusion Criteria: 
1. Any clinically significant abnormal finding at physical examination at 
screening. 
2. Clinically significant abnormal laboratory test results or positive 
serology test results for hepatitis B surface antigen (HBsAg), hepatitis 
C virus (HCV) antibody, or human immunodeficiency virus (HIV) 
antigen and antibody, at screening. 
3. Any of the following laboratory parameters above the upper limit of 
normal (ULN) values at screening or baseline (Day -1): aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), direct 
bilirubin, indirect bilirubin, and total bilirubin. Only abnormal values up 
to 1.5x ULN may be repeated once for confirmation to below ULN. 
4. Positive pregnancy test or lactating female participant. 
5. Positive urine drug screen, urine cotinine test, or alcohol breath test. 
6. Positive test for coronavirus 2019 (COVID-19) at admission. 
7. Known allergic reactions or hypersensitivity to camlipixant, gemfibrozil 
(participants in Part 1 only), dabigatran etexilate or dabigatran 
(participants in Part 2 only), or other related drugs, or to any excipient 
in the formulation. 
8. Clinically significant ECG abnormalities (for example, Fridericia’s 
corrected QT interval [QTcF] > 450 ms) or vital signs abnormalities 
(systolic blood pressure lower than 90 or over 140 mmHg, diastolic 
blood pressure lower than 50 or over 90 mmHg, or heart rate less than 
50 or over 100 bpm) at screening. 
9. History of drug abuse within 1 year prior to screening or use of drugs 
(such as cocaine, phencyclidine [PCP], crack, opioid derivatives 
including heroin, and amphetamine derivatives) within 3 months prior 
to screening, except for cannabis, hashish, or any products containing 
either, which are not allowed within 1 month prior to screening. 
10. History of alcohol abuse within 1 year prior to screening or regular use 
of alcohol within 6 months prior to screening that exceeds 10 units for 
women or 15 units for men of alcohol per week (1 unit = 340 mL of 
beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%). 
11. History of gastrointestinal disorders, such as stomach ulcers, irritable 
bowel syndrome (IBS), ulcerative or pseudomembranous colitis, 
intestinal obstruction, previous liver disease or hepatic dysfunction 
(including primary biliary cirrhosis), hyperbilirubinemia, jaundice, or 
elevated liver enzymes. 
12. Known Gilbert, Rotor, Crigler-Najjar, or Dubin-Johnson syndrome. 
13. 
 
.  
14. History of gallbladder disease, including cholelithiasis. 
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15. History of renal dysfunction and those with estimated creatinine 
clearance (CrCl) less than 60 mL/min. 
16. Participants in Part 1 only: History of myoglobinuria, myopathy, 
myalgia, myositis or rhabdomyolysis. 
17. Participants in Part 1 only: History of Type I hyperlipoproteinemia. 
18. Participants in Part 2 only: Participants with haemorrhagic 
manifestations, clinically significant active bleeding, including 
gastrointestinal bleeding, bleeding diathesis, spontaneous or 
pharmacological impairment of haemostasis. 
19. Participants in Part 2 only: Participants with lesions, diseases, or 
procedures at risk of clinically significant bleeding/haemorrhagic risks, 
such as congenital or acquired coagulations disorders, 
thrombocytopenia or functional platelet defects, recent cerebral 
infarction (haemorrhagic or ischemic) within the last 6 months, active 
ulcerative gastrointestinal disease (including peptic ulcer) with recent 
gastrointestinal bleeding, bacterial endocarditis, recent biopsy or major 
trauma, brain, spinal or ophthalmic surgery, prosthetic heart valves, or 
hemodynamically significant rheumatic heart disease. 
20. Participants in Part 2 only: History of antiphospholipid disease. 
21. Participants in Part 2 only: Participants having undergone any major 
surgery within 6 months prior to the start of the study, unless deemed 
otherwise by the Investigator. 
22. Participants in Part 2 only: Any of the following laboratory parameters 
outside the normal ranges at screening or baseline (Day -1): 
prothrombin time (PT) and activated partial thromboplastin time 
(aPTT). 
23. Use of medications for the timeframes specified below, with the 
exception of medications exempted by the Investigator on a case-by-
case basis because they are judged unlikely to affect the PK profile of 
the study drug or participant safety (e.g., topical drug products without 
significant systemic absorption): 
a. depot injection or implant within 3 months prior to dosing; 
b. any drug known to induce or inhibit hepatic drug metabolism, 
including St. John’s wort, within 30 days prior to dosing or 
10 half-lives, whichever is longer; 
c. prescription medications within 14 days prior to dosing; 
d. any vaccine, including COVID-19 vaccine, within 14 days prior to 
dosing; 
e. over-the-counter (OTC) medications and natural health products 
(including herbal remedies, homeopathic and traditional medicines, 
probiotics, food supplements such as vitamins, minerals, amino 
acids, essential fatty acids, and protein supplements used in sports) 
within 7 days prior to dosing, with the exception of the occasional 
use of acetaminophen (up to 2 g daily). 


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24. Participation in a clinical research study involving the administration of 
an investigational or marketed drug or device within 30 days prior to 
dosing, administration of a biological product in the context of a clinical 
research study within 90 days prior to dosing, or concomitant 
participation in an investigational study involving no drug or device 
administration. 
25. Donation of plasma within 7 days prior to dosing or donation or loss of 
500 mL or more of whole blood within 8 weeks prior to dosing. 
26. Any reason which, in the opinion of the Investigator, would prevent the 
participant from participating in the study. 
Study Treatments: 
Participants will receive: 
• 
Camlipixant (BLU-5937) 1 x 50 mg tablet administered under 
fasting conditions 
 on Day 1 and Day 9 (Part 1), or 
1 x 50 mg tablet for 6 consecutive days from Day 5 to Day 9 as 
, (total daily dose 100 mg), and as 
 
(
 in the morning of Day 10 (Part 2). 
• 
On Day 9 (Part 1), camlipixant will be administered 1 hour 
(± 2 minutes) after morning administration of gemfibrozil (Part 1). 
• 
Gemfibrozil 
 mg tablet administered 
 
 mg), for 7 consecutive days from Day 5 to 
Day 11 (Part 1). Administration will occur before 
 
except for the morning dose on Day 9. 
• 
Dabigatran etexilate 
 mg capsule administered under fasting 
condition in the 
 on Day 1 and Day 10 (Part 2). 
• 
On Day 10 (Part 2), dabigatran etexilate will be co-administered at 
the same time with the 
administration of camlipixant 
(Part 2). 
On Day 1: No food will be allowed from at least 10 hours before 
camlipixant (Part 1) or dabigatran etexilate (Part 2) dosing until at least 
4 hours after dosing. 
On Day 9 (Part 1) or Day 10 (Part 2): No food will be allowed from at least 
10 hours before gemfibrozil (Part 1) or camlipixant/dabigatran etexilate 
(Part 2) dosing until at least 4 hours after camlipixant (Part 1) or 
camlipixant/dabigatran etexilate (Part 2) dosing. 
On Days 5 to 8, evening of Day 9, and Days 10 and 11 (Part 1): 
Gemfibrozil will be administered approximately 30 minutes (±10 minutes) 
before a standard morning/evening meal. 
On Days 5 to 9 (Part 2): No food will be allowed from at least 2 hours 
before morning camlipixant dosing until 1-hour post-morning dose. A 
normo-caloric breakfast will be served at least 1 hour after camlipixant 
administration. 
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Study Procedures: 
Blood samples for PK analysis will be collected and safety procedures will 
be performed at pre-defined times throughout the study as specified in 
Table 1. Schedule of Assessments for Part 1 and Table 2. 
Schedule of 
Assessments for Part 2. 
Participants will be monitored throughout the study by the clinical staff for 
AEs and concomitant medication use. 
Statistical Analyses: 
PK analysis: 
 
 
 
 
 
 
 
 
 
Concentrations for gemfibrozil (Part 1) and camlipixant (Part 2) will be 
tabulated. They will be presented as supportive data. Descriptive statistics 
on pre-morning dose concentrations of gemfibrozil in Part 1 (Days 7, 8 and 
9) and camlipixant in Part 2 (Days 8, 9, and 10) will be performed to 
evaluate the attainment of steady-state. 
 
 
 
 
 
 
 
 The sample may be also used to investigate 
other possible exploratory markers as deemed necessary  
Metabolites of camlipixant may be assayed at a later time, if deemed 
necessary. 
Safety and tolerability analysis: 
Safety and tolerability of camlipixant alone (Part 1 and Part 2) and in 
combination with gemfibrozil (Part 1) or dabigatran etexilate (Part 2) will 
be evaluated through the assessment of AEs, SAEs, AEMIs (i.e., 
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seriousness, severity, relationship to the study drug and the interacting drug, 
outcome, duration, and management), vital signs, 12-lead ECGs, clinical 
laboratory tests, and physical examinations. Treatment-emergent adverse 
events (TEAEs) will be tabulated by treatment. Safety and tolerability data 
will be reported using descriptive statistics. 
A Summary Table of study procedures is presented in Appendix 1. 


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Table 1. 
Schedule of Assessments for Part 1 
Study Stage 
Screening 
Baseline 
Treatment 
Follow-up 
phone call 
Day 
-28 to -1 
-1 
1 
2-3 
4 
5 
6-8 
9 
10 
11 
12 
19 ± 2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
Confinement 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Discharge/ET 
 
 
 
 
 
 
 
 
 
 
X14 
 
Follow-up phone call 
 
 
 
 
 
 
 
 
 
 
 
X15 
Study drug administration 
 
 
 
 
 
 
 
 
Camlipixant1 
 
 
X 
 
 
 
 
X 
 
 
 
 
Gemfibrozil2 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
 
 
 
Blood samples for PK analysis of 
camlipixant3 
 
 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Blood samples for PK analysis of 
gemfibrozil4 
 
 
 
 
 
X 
X 
X 
 
 
 
 
Blood sample for pharmacogenomic 
analysis 
 
X 
 
 
 
 
 
 
 
 
 
 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination5 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
Body measurements (height, weight, BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signs6 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
12-lead ECG7 
X 
 
X 
 
 
X 
 
X 
 
 
X 
 
Serology tests8 
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests (biochemistry, 
hematology, and coagulation)9 
X 
X 
 
 
 
X 
 
X 
 
 
X 
 
Urinalysis10 
X 
X 
 
 
 
X 
 
X 
 
 
X 
 
FSH (for post-menopausal females)11 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy tests12 
X 
X 
 
 
 
 
 
 
 
 
X 
 


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Study Stage 
Screening 
Baseline 
Treatment 
Follow-up 
phone call 
Day 
-28 to -1 
-1 
1 
2-3 
4 
5 
6-8 
9 
10 
11 
12 
19 ± 2 
Drug, cotinine, and alcohol screens 
X 
X 
 
 
 
 
 
 
 
 
 
 
COVID-19 test 
 
X 
 
 
X 
 
 
 
 
 
 
 
Monitoring and recording of AEs, SAEs, 
AEMIs, and prior/concomitant medication 
use13 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; AEMI =adverse event of medical interest; BMI = body mass index; CK = creatine kinase; COVID-19 = coronavirus 2019; 
ECG = electrocardiogram; ET = early termination; FSH = follicle-stimulating hormone; HbsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = 
human immunodeficiency virus; LFT = liver function test; PK = pharmacokinetic; SAE = serious adverse event. 
1 
On Day 9, camlipixant will be administered 1 hour (± 2 minutes) after
 administration of gemfibrozil. 
2 
Administration of gemfibrozil 
, will occur at approximately the 
 and evening from Days 5 to 11. A time 
window of ± 10 minutes from the scheduled dosing time will be allowed, as long as the 1-hour (± 2 minutes) time interval between gemfibrozil and 
camlipixant dosing on Day 9 is respected. 
3 
A total of 19 blood samples will be collected for PK analysis of camlipixant on Day 1 and Day 9: at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 
12, 15, 18, 24, 48, and 72 hours post-dose. Refer to Table 3 for more details. 
4 
A total of 5 blood samples will be collected for PK analysis of gemfibrozil pre-morning dose on Days 5, 6, 7, 8, and 9. Refer to Table 3 for more details. 
5 
A complete physical examination will be performed at screening. A brief physical examination will be performed on Day -1, in the evening of Day 8, and at 
discharge on Day 12 (or ET). 
6 
Blood pressure, heart rate, respiratory rate, and oral temperature will be measured at screening and discharge on Day 12 (or ET). Blood pressure and heart 
rate will be measured before camlipixant dosing on Day 1 and before gemfibrozil dosing on Day 9. 
7 
12-lead ECG will be measured at screening, before camlipixant dosing on Day 1, before gemfibrozil dosing on Day 5 and Day 9, at approximately 1 hour 
post-dosing of camlipixant on Day 9, and at discharge on Day 12 (or ET). 
8 
Serology tests include HbsAg, HCV antibody, HIV antigen and antibody. 
9 
Standard biochemistry (including LFT and CK), hematology, and coagulation tests will be performed at screening, on Day -1, before gemfibrozil dosing on 
Day 5 and Day 9, and at discharge on Day 12 (or ET). 
10 Urinalysis tests will be performed at screening, on Day -1, before gemfibrozil dosing on Day 5 and Day 9, and at discharge on Day 12 (or ET). 
11 FSH levels will be measured at screening to confirm the post-menopausal status. 
12 A urine pregnancy test will be performed at screening and at discharge on Day 12 (or ET), and a serum pregnancy test will be performed on Day -1. If there 
is a positive pregnancy result following the first study drug administration, a Pregnancy Notification form is to be completed and submitted to the Sponsor. 
13 All AEs, SAEs, and AEMIs will be closely monitored and reported as indicated in safety section 8.4. Following dosing on Day 1 until the end of the study, 
participants who spontaneously report
 
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Reported 
 will continue to be followed until resolved. Testing for COVID-19 (SARS-CoV-2) should be performed for participants 
reporting any ongoing or recent (within 1 week of ending) 
 
14 In case of ET, discharge procedures will be performed as soon as possible. 
15 A safety follow-up phone call will be performed 7 ± 2 days after discharge. 
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Table 2. 
Schedule of Assessments for Part 2 
Study Stage 
Screening 
Baseline 
Treatment 
Follow-up 
phone call 
Day 
-28 to -1 
-1 
1 
2 
3 
4 
5 
6-9 
10 
11-12 
13 
20 ± 2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
Confinement 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Discharge/ET 
 
 
 
 
 
 
 
 
 
 
X14 
 
Follow-up phone call 
 
 
 
 
 
 
 
 
 
 
 
X15 
Study drug administration 
 
 
 
 
 
 
 
 
 
 
 
 
Dabigatran etexilate1 
 
 
X 
 
 
 
 
 
X 
 
 
 
Camlipixant2 
 
 
 
 
 
 
X 
X 
X 
 
 
 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
 
 
 
Blood samples for PK analysis of 
dabigatran3 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
 
Blood samples for PK analysis of 
camlipixant4 
 
 
 
 
 
 
X 
X 
X 
 
 
 
Blood sample for pharmacogenomic 
analysis 
 
X 
 
 
 
 
 
 
 
 
 
 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination5 
X 
X 
 
 
 
 
X 
 
 
X 
 
Body measurements (height, weight, BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signs6 
X 
 
X 
 
 
 
 
 
X 
 
X 
 
12-lead ECG7 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
Serology tests8 
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests (biochemistry, 
hematology, and coagulation)9 
X 
X 
 
 
 
 
X 
X 
 
 
X 
 
Urinalysis10 
X 
X 
 
 
 
 
X 
X 
 
 
X 
 
FSH (for post-menopausal females)11 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy tests12 
X 
X 
 
 
 
 
 
 
 
 
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Study Stage 
Screening 
Baseline 
Treatment 
Follow-up 
phone call 
Day 
-28 to -1 
-1 
1 
2 
3 
4 
5 
6-9 
10 
11-12 
13 
20 ± 2 
Drug, cotinine, and alcohol screens 
X 
X 
 
 
 
 
 
 
 
 
 
 
COVID-19 test 
 
X 
 
 
 
X 
 
 
 
 
 
 
Monitoring and recording of AEs, SAEs, 
AEMIs, and prior/concomitant medication 
use13 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; AEMI =adverse event of medical interest; aPTT = activated partial thromboplastin time; BMI = body mass index; CK = 
creatine kinase; COVID-19 = coronavirus 2019; CrCl = creatinine clearance; ECG = electrocardiogram; ET = early termination; FSH = follicle-stimulating 
hormone; HbsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; LFT = liver function test; PK = 
pharmacokinetic; PT = prothrombin time; SAE = serious adverse event. 
1 
On Day 10, dabigatran etexilate will be co-administered with camlipixant at the same time. Camlipixant will be swallowed first, followed immediately by 
dabigatran. The entire procedure should be completed within 2 minutes. 
2 
Administration of camlipixant 
, will occur at approximately the same time in the 
and in the evening from Days 5 to 9, and in 
the 
of Day 10. A time window of ± 10 minutes from the scheduled dosing time will be allowed, as long as the co-administration of camlipixant and 
dabigatran etexilate at the same time on Day 10 is respected. 
3 
A total of 21 blood samples will be collected for PK analysis of dabigatran on Day 1 and Day 10: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 
10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose. Refer to Table 4 for more details. 
4 
A total of 5 blood samples will be collected for PK analysis of camlipixant pre-morning dose on Days 5, 7, 8, 9 and 10. Refer to Table 4 for more details. 
5 
A complete physical examination will be performed at screening. A brief physical examination will be performed on Day -1, in the evening of Day 9, and at 
discharge on Day 13 (or ET). 
6 
Blood pressure, heart rate, respiratory rate, and oral temperature will be measured at screening and discharge on Day 13 (or ET). Blood pressure and heart 
rate will be measured before dabigatran etexilate dosing on Day 1 and before camlipixant dosing on Day 10. 
7 
12-lead ECG will be measured at screening, before dabigatran etexilate dosing on Day 1, before camlipixant dosing on Day 5 and Day 10, and at discharge 
on Day 13 (or ET). 
8 
Serology tests include HbsAg, HCV antibody, and HIV antigen and antibody. 
9 
Standard biochemistry (including LFT and CK), hematology, and coagulation tests will be performed at screening, on Day -1, before camlipixant dosing on 
Day 5, the day before dabigatran dosing on Day 9, and at discharge on Day 13 (or ET). All subjects should have PT, aPTT and CrCl measured. The PT and 
aPTT should be within the normal range and the CrCl value should be more than 60 mL/min for each subject before dabigatran dosing in order to prevent or 
avoid the possibility of bleeding. 
10 Urinalysis will be performed at screening, on Day -1, before camlipixant dosing on Day 5, the day before dabigatran dosing on Day 9, and at discharge on 
Day 13 (or ET). 
11 FSH levels will be measured at screening to confirm the post-menopausal status. 
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12 A urine pregnancy test will be performed at screening and at discharge on Day 12 (or ET), and a serum pregnancy test will be performed on Day -1. If there 
is a positive pregnancy result following the first study drug administration, a Pregnancy Notification form is to be completed and submitted to the Sponsor. 
13 All AEs, SAEs, and AEMIs will be closely monitored and reported as indicated in safety section 8.4. Following dosing on Day 5 until the end of the study, 
participants who spontaneously report taste disturbance as an AE will be asked to provide additional characterization of their taste disturbance.
 
 
 
14 In case of ET, discharge procedures will be performed as soon as possible. 
15 A safety follow-up phone call will be performed 7 ± 2 days after discharge. 
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1. 
Introduction 
1.1 
Background Information 
Camlipixant (previously identified as BLU-5937) is a small molecule of the 
 
 that is developed for the treatment of refractory (or unexplained) chronic cough 
(RCC). It has been shown to be a potent, selective, and non-competitive P2X3 homotrimeric 
receptor antagonist. P2X3 receptors are adenosine triphosphate (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 refractory 
RCC. Camlipixant was shown to reduce significantly cough frequency in patients with baseline 
awake cough frequency
 coughs/hour in a Phase 2b clinical study.
 
Of note, 
the high selectivity of camlipixant for the P2X3 homotrimeric receptor versus P2X2/3 
heterotrimeric receptor should reduce the taste disturbance AEs that have been associated to 
P2X2/3 and observed with other less selective P2X3 antagonists  
1.2 
Nonclinical 
 
 
 
 
 
 
 
 
The toxicology of camlipixant has been studied in several preclinical species. Selected findings 
are presented below. Please refer to the Investigator’s Brochure (IB) for a complete description 
and summary. Regarding the male reproductive system, camlipixant was shown to have effects 
in the testis with decreased sperm in the epididymis upon long-term administration in animal 
toxicity studies (26 weeks in rat and 39 weeks in dog). These findings were fully reversible and 
were not observed with shorter-term dosing (28 days toxicity study, and a fertility study where 
male rats were administered camlipixant up to 60 days)  However, it is not known whether the 
effects seen in animals will also occur in men dosed with camlipixant. Since only the long-term 
preclinical studies have resulted in testicular toxicity and that this has been observed to be 
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reversible, it is considered that the risks to healthy male adults receiving single doses, and with a 
suitable washout period between doses, is minimal.  
Lens and corneal opacities have been observed upon chronic 26- and 39-week administration in 
rats and dogs, respectively. These were minor in terms of severity and were considered 
non-adverse as they are not expected to affect the vision. These were not observed with 
short-term dosing and the risks to healthy participants receiving single doses is considered 
minimal  
1.3 
Clinical 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
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To date, approximately 560 participants have been exposed to camlipixant at doses ranging from 
12.5 mg to 1200 mg as single or multiple BID doses for up to 4 weeks in Phase 1 and Phase 2 
studies. Camlipixant was found to be generally well tolerated in healthy adult participants, 
participants with RCC, and participants with chronic pruritis associated with atopic dermatitis. 
Overall, 210 healthy participants have been exposed to camlipixant at doses ranging from 
12.5 mg to 1200 mg as single or multiple doses in Phase 1 studies. There were no deaths or 
SAEs reported during these studies. The most common TEAEs (camlipixant/placebo) following 
administration were headache (10.0% / 3.2%), somnolence (9.5% [possibly all related to 
in a DDI study]) / 0.0%), dysgeusia (9.0% / 1.6%), constipation (6.2% / 0.0%), 
dizziness (5.2% / 0.0%), nausea (4.3% / 4.8%), hypoesthesia (3.8% / 0.0%), diarrhea (3.3% / 
0.0%), dyspepsia (2.4% / 1.6%), and abdominal pain (0.0% / 3.2%). There were no significant 
changes in vital signs or ECG parameters at any dose level. There were no significant changes in 
laboratory parameters, except for two isolated cases of mild elevations in liver enzymes (ALT 
and/or AST), 1 case at 400 mg BID in the FIH and one case at 200 mg BID in a DDI study 
(BUS-P1-02). In both cases, these elevations in liver enzymes were not associated with a 
concomitant increase in bilirubin or with clinical symptoms of liver injury. There was a slight 
trend of increased bilirubin in the FIH study (especially at 400 mg BID) and 1 case with 200 mg 
BID in a DDI study (BUS-P1-02; both representing a supra-therapeutic dose), which were not 
associated with any concomitant increases in liver enzymes. The mild elevation in bilirubin in 
the absence of increased liver enzyme levels is likely due to the drug’s interference in bilirubin 
disposition through OATP inhibition and is likely to represent a benign process. Overall, 
3 participants were discontinued from the Phase 1 clinical studies due to TEAEs, all from the 
DDI (BUS-P1-02) study at the 200 mg BID dose: 2 participants had mild rash (camlipixant) and 
one of these participants had increased AST and ALT levels (sulfasalazine alone)  
 
 
 
Refer to the IB v.5 and the IB addendum for detailed background information on camlipixant  
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1.4 
Background Information on Gemfibrozil 
Gemfibrozil is an antihyperlipidemic agent indicated as an adjunct to diet and other therapeutic 
measures for: 1) treatment of adult patients with very high serum triglyceride levels, Fredrickson 
classification Type
 
 
 
 
. The maximum recommended daily dose is 
1500 mg. AEs associated with gemfibrozil are listed in the Product Monograph.5 
Gemfibrozil is a lipid regulating agent which decreases serum triglycerides and total cholesterol, 
and increases high density lipoprotein cholesterol. The mechanism of action has not been 
definitely established. In man, gemfibrozil has been shown to inhibit peripheral lipolysis and to 
decrease the hepatic extraction of free fatty acids, thus reducing hepatic triglyceride production. 
Gemfibrozil also inhibits the synthesis and increases clearance of very low density lipoprotein 
(VLDL) carrier apolipoprotein B, leading to a decrease in VLDL.5 
Gemfibrozil is completely absorbed after oral administration. Peak plasma levels occur in 1 to 
2 hours following single doses. Plasma levels appear proportional to dose and do not 
demonstrate accumulation across time following multiple doses. Gemfibrozil PK is affected by 
the timing of meals relative to time of dosing. In one study, both the rate and extent of absorption 
of the drug were significantly increased when administered 0.5 hours before meals. Average area 
under the concentration-time curve (AUC) was reduced by 14 to 44% when gemfibrozil was 
administered after meals compared to 0.5 hour before meals. In a subsequent study, rate of 
absorption of gemfibrozil was maximum when administered 0.5 hour before meals with the Cmax 
50-60% greater than when given either with meals or fasting. In this study, there were no 
significant effects on AUC of timing of dose relative to meals.5 
Three metabolic pathways have been identified. The first metabolic pathway is that of 
conjugation of gemfibrozil and its metabolites. The second, and presumably the principal route, 
involves hydroxylation of the meta-methyl group of gemfibrozil, yielding a benzyl alcohol 
(Metabolite II) that undergoes rapid oxidation to a benzoic acid metabolite (Metabolite III, the 
major metabolite). The third pathway involves hydroxylation of the aromatic ring to a phenol 
(Metabolite I) which is further converted to a compound (Metabolite IV) with no intact 
carboxylic acid function, but which is phenolic in nature. In human subjects, approximately 70% 
of a given dose is excreted in the urine, primarily as the glucuronide conjugate, with less than 2% 
excreted as unchanged gemfibrozil; 6% of the dose is accounted for in the feces. The mean 
half-life was approximately 1.5 hours following single doses and 1.3 hours following multiple 
doses.5 
Gemfibrozil inhibits CYP 2C8 isoenzyme. This irreversible inactivation of CYP2C8 is mediated 
by Gemfibrozil-1-O-beta-glucuronide (GEM-1-O-gluc), a metabolite of gemfibrozil. 
Gemfibrozil is also known to potently inhibit CYP2C9 activity. Although gemfibrozil also acts 
as an OATP1B1 inhibitor, a transporter involved in disposition of endogenous compounds such 
as bilirubin, this pathway is not believed to be important for camlipixant metabolism. 
Gemfibrozil is highly bound to plasma proteins and there is potential for displacement 
interactions with other drugs.5 
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1.5 
Background Information on Dabigatran Etexilate 
Dabigatran etexilate is a direct thrombin inhibitor, indicated for the prevention of venous 
thromboembolic events (VTE) in patients who have undergone elective total hip replacement 
(THR) or total knee replacement (TKR) surgery, treatment of venous thromboembolism events 
(deep vein thrombosis [DVT], pulmonary embolism [PE]) and prevention of recurrent DVT and 
PE, and prevention of stroke and systemic embolism in patients with atrial fibrillation. In most 
indications, for patients with creatinine clearance (CrCl) >30 mL/min, the recommended dose of 
dabigatran etexilate is 150 mg taken orally, BID, with food or on an empty stomach. Dosage may 
be individualized according to the patient’s age and medical condition. AEs associated with 
dabigatran etexilate are listed in the Product Monograph.6 
Dabigatran etexilate is a prodrug which does not exhibit anticoagulant activity itself. Following 
oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by 
esterase-catalysed hydrolysis in plasma and in the liver. Dabigatran is a competitive, reversible 
direct thrombin inhibitor and is the main active principle in plasma. Since thrombin (serine 
protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its 
inhibition prevents the development of thrombus. Dabigatran also inhibits free thrombin, 
fibrin-bound thrombin and thrombin-induced platelet aggregation.6 
After oral administration, dabigatran etexilate is rapidly and completely converted to dabigatran. 
The PK profile of dabigatran in plasma is characterized by a rapid increase in plasma 
concentrations with Cmax attained 0.5 to 2.0 hours post-administration. The absolute 
bioavailability of dabigatran following oral administration of dabigatran etexilate was 
approximately 6.5 %. The oral bioavailability may be increased by 75% (about 1.8 -fold) 
compared to the reference capsule formulation when the pellets are taken without the 
hydroxypropylmethylcellulose (HPMC) capsule shell. Hence, the integrity of the HPMC 
capsules should always be preserved in clinical use to avoid unintentionally increased 
bioavailability of dabigatran etexilate. As such, dabigatran etexilate should be taken orally with 
the entire capsule to be swallowed whole. The capsule should not be chewed, broken, or opened. 
Food does not affect the bioavailability of dabigatran but delays the time-to-peak plasma 
concentrations by 2 hours.6 
The cleavage of the prodrug dabigatran etexilate by esterase-catalysed hydrolysis to the active 
principle dabigatran is the predominant metabolic reaction. Dabigatran is metabolised in the liver 
by conjugation with activated glucuronic acid forming pharmacologically active 
acylglucuronides. Four positional isomers, 1-O, 2-O, 3-O, 4-O-acylglucuronide exist, each 
accounting for <10% of total dabigatran in plasma. Cytochrome P450 metabolic enzymes are not 
involved in dabigatran metabolism.6 
After Cmax, plasma concentrations of dabigatran showed a biexponential decline with a mean 
terminal half-life of approximately 11 hours in healthy elderly subjects. Following administration 
of multiple doses, a terminal half-life of about 12 to 14 hours was observed, with the half-life 
independent of dose. Cmax and AUC were dose-proportional. After an intravenous dose, the 
dabigatran-derived radioactivity was eliminated primarily in the urine (85%). Faecal excretion 
accounted for 6% of the administered dose. Hepatic elimination via the bile represents a minor 
elimination pathway (approximately 20% of the administered dose). Dabigatran is eliminated 


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primarily in the unchanged form in the urine, at a rate of approximately 100 mL/min 
corresponding to the glomerular filtration rate.6 
1.6 
Study Rationale 
Part 1: 
 
 
 
 
 
 
 
 
Metabolic inhibition may result in increased plasma concentrations of drugs and/or their active 
metabolite(s). These increased plasma concentrations may lead to toxicity associated with these 
drugs. 
Therefore, the purpose of Part 1 is to assess, in vivo, the potential of camlipixant to be a victim of 
DDIs precipitated by inhibition of the CYP2C8 enzyme believed to be involved in the 
biotransformation of camlipixant. In accordance with the recommendations provided in the FDA 
Guidance for Clinical Drug Interaction Studies – Cytochrome P450 Enzyme- and 
Transporter-Mediated Drug Interactions (2020),7 multiple doses of the CYP inhibitor 
gemfibrozil8 will be administered to evaluate the effect on the PK of single dose camlipixant. 
Gemfibrozil is a clinically validated, strong inhibitor for CYP2C8.8 Its use in the current clinical 
DDI study will allow to potentially corroborate the findings related to CYP2C8 inhibition from 
the previously conducted PBPK study. 
Part 2: 
Based on PBPK modeling predicting camlipixant as a perpetrator in DDIs, a weak interaction 
may be seen with the P-gp substrate dabigatran while no other interactions are anticipated with 
substrates of CYP or transporters. PBPK simulations performed using the Ki for P-gp inhibition 
showed no significant interaction with digoxin and dabigatran. Using a 15-x reduced P-gp Ki, a 
small increase in Cmax (28%) and no significant increase in AUC were predicted for digoxin 
while a 56% and 44% increase in Cmax and AUC was predicted for dabigatran  
Therefore, the purpose of Part 2 is to assess, in vivo, the potential of camlipixant to act as a 
perpetrator in DDIs through inhibition of the P-gp transporter. In accordance with the 
recommendations provided in the FDA Guidance for Clinical Drug Interaction Studies – 
Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (2020),7 a single dose 
of dabigatran etexilate, a clinically validated substrate of P-gp,8 will be administered alone and in 
combination with camlipixant, in order to evaluate the impact of camlipixant on P-gp efflux. The 
choice of dabigatran etexilate will allow to verify clinically the observations on P-gp from the 
PBPK study. 
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1.6.1 
Analytes to Measure 
The analytes to be measured will include the investigational drug camlipixant (Parts 1 and 2), as 
well as gemfibrozil (Part 1) and dabigatran (Part 2). 
Metabolites of camlipixant may be assayed at a later time, if deemed necessary. 
Dabigatran etexilate is a prodrug and, after oral administration, it is rapidly and completely 
converted to dabigatran, which is the active form in plasma after oral administration. The analyte 
of interest will be dabigatran. Both free dabigatran (non-conjugated) and total dabigatran will be 
analyzed. Results for the free form will be used as supportive data. 
In this clinical study, perpetrator drugs (gemfibrozil in Part 1 and camlipixant in Part 2) will be 
administered in a controlled setting i.e., within a clinical research unit with directly observed 
dosing. Thus, it is not relevant to measure extensively gemfibrozil in Part 1 or camlipixant in 
Part 2 blood levels. Accordingly, as participants will be confined to the clinical unit the full 
duration of the study, only sparse samples for gemfibrozil in Part 1 and camlipixant in Part 2 will 
be collected to provide information on attainment of steady-state, or to help explain any aberrant 
results. 
1.6.2 
Rationale for the Dose and Dosing Regimen 
Camlipixant is a film-coated, immediate release tablet, available in different strengths from 12.5 
to 100 mg.1 In Part 1, one tablet of 50 mg camlipixant will be administered as a single dose on 
Day 1 and Day 9. According to the FDA guidance, single dose administration of the substrate 
drug is acceptable if the substrate does not show time-dependent-PK, and, if the substrate drug 
has dose-proportional PK, any dose in the linear range may be used.7 The 50 mg dose of 
camlipixant was chosen because it is the highest clinically relevant dose currently being tested in 
Phase 3 studies. In addition, since the PK are linear, the drug interaction at a 50 mg dose is 
anticipated to be representative of the interactions across the clinically relevant range. In Part 2, 
camlipixant will be administered at 50 mg BID from Days 5 through 9, and in the morning of 
Day 10. According to the FDA guidance,7 the dose of the perpetrator drug used in DDI studies 
should maximize the possibility of identifying a DDI, by using the maximum approved dose and 
shortest dosing interval. In a population PK model, exposure response modeling confirmed that 
the camlipixant 50 mg BID dose should provide near maximal or maximal participant benefit 
with the highest level of confidence. Doses higher than 50 mg BID (62.5, 75, and 200 mg BID) 
did not provide a substantial increase in the maximum effect. Accordingly, the highest proposed 
dose and dosing regimen of camlipixant for Phase 3 clinical trials is 50 mg BID. Considering the 
half-life of camlipixant is 4 to 9 hours  a 5-day lead-in period with camlipixant ensures 
attainment of steady-state before co-administration with dabigatran etexilate on the 6th day 
(Day 10) of dosing. 
For gemfibrozil, the 
 
) 30 minutes before the
 and 
meal.5 Therefore, in line with FDA guidance7 and commonly used dose in the 
literature,9,10 a 
mg dose of gemfibrozil will be administered 
 
 A 4-day lead-in period from Days 5 to 8 before co-administration 
with camlipixant on the 5th day (Day 9) ensures attainment of steady-state and inhibition of 
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CYP2C8 by the day of co-administration. The last gemfibrozil dose will be administrated on the 
evening of Day 11, before-last PK sampling timepoint of camlipixant, to maintain inhibition. 
Other than the morning dose that will be co-administered with camlipixant on Day 9, all other 
gemfibrozil administrations will occur 30 minutes (±10 minutes) before a standard 
morning/evening meal. 
The recommended dose of dabigatran etexilate is 
 mg taken orally, 
, with food or on an 
empty stomach.6 Following recommendations from the FDA guidance,7 one capsule of 
mg 
of 
 
 will be administered alone as a single dose on Day 1 and co-administered 
with camlipixant on Day 10. This dose is commonly used in the literature.11 
1.6.3 
Pharmacogenomic Testing 
One blood sample for pharmacogenomic testing will be taken on Day -1
 
. The sample may be also used to investigate other possible exploratory markers as 
deemed necessary. 
1.6.4 
Rationale for the Study Population 
A healthy volunteer population has been selected for the study because healthy participants with 
no concomitant diseases and using no concomitant medications represent a homogenous 
population allowing for proper evaluation of the PK, safety, and tolerability of a drug without 
confounding factors. 
To date, approximately 560 participants have been exposed to camlipixant at doses ranging from 
12.5 mg to 1200 mg as single or multiple BID doses for up to 4 weeks in Phase 1 and Phase 2 
studies. Camlipixant was found to be generally well tolerated in healthy adult participants as 
outlined in Section 1.3. Embryo-fetal development (EFD) and female and male fertility studies 
on camlipixant in rats and rabbits did not identify any findings of concern for humans, including 
teratogenicity, at the proposed clinical doses (safety margins >20 at the 50 mg single dose 
proposed in this current study). The no observed adverse effect levels (NOAEL) for EFD toxicity 
in pregnant rats was 100 mg/kg/day with lower maternal body weights, lower fetal body weights, 
and increased incidence of fetal tail abnormalities and skeletal variations observed at the highest 
dose tested (250 mg/kg/day). No test article-related effects on maternal survival, clinical 
findings, ovarian and uterine parameters or gross macroscopic findings were observed at any 
camlipixant dose level evaluated. The NOAEL for fertility and reproductive effects and early 
embryonic development in female rats was 150 mg/kg/day due to adverse lower fertility and 
fecundity indices, lower number of implantation sites, and post implantation loss observed at 
450 mg/kg/day. In the EFD study in pregnant rabbits, based upon the maternal clinical signs and 
lower body weight gain and food consumption at 450 mg/kg/day, the NOAEL for maternal 
toxicity was considered to be 200 mg/kg/day while the NOAEL for EFD toxicity is considered to 
be 450 mg/kg/day. In the male fertility study, the no observed effect level (NOEL) for paternal 
toxicity and male mating, fertility, sperm parameters, and reproductive outcome is considered to 
be 450 mg/kg/day  There have been no clinical studies of camlipixant conducted in pregnant 
women. 
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At oral doses of approximately 95 and 325 mg/kg/day in male and female rats, gemfibrozil 
produced a dose-related suppression of fertility but had no effect on length of gestation, duration 
of parturition, litter size, or embryonic or fetal wastage. Treated males were responsible for the 
reduced fertility rate, probably because of the marked suppression of weight gain they 
experienced. In pregnant rats and rabbits at doses of 81 and 281 mg/kg, examination of fetuses 
removed from treated rats and rabbits one day before expected parturition disclosed no 
significant effects on either litter or fetal characteristics, nor were significant malformations 
found among almost 400 offspring from 36 litters of treated rats or 100 fetuses from 22 litters of 
treated rabbits. Among women, gemfibrozil is to be discontinued several months prior to 
conception. Because of the potential for tumorgenicity shown in rats, a decision should be made 
whether to discontinue nursing or discontinue the drug for nursing mothers.5 
In teratology studies of dabigatran in rats and rabbits, a slight effect on the morphogenesis of 
foetuses was observed in rats at 200 mg/kg (free base equivalent). In a fertility study in rats, a 
slight decrease in corpora lutea and an increase in pre-implantation loss led to a decrease in the 
mean number of implantations in the 200 mg/kg (free base equivalent) dose group. Dabigatran 
decreased the number of implantations when male and female rats were treated at dosages about 
2.6 to 3.0x the human exposure at maximum recommended human dose (MRHD) prior to mating 
and up to implantation. Treatment of pregnant rats after implantation at the same dose increased 
the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. 
Although dabigatran increased the incidence of delayed or irregular ossification of fetal skull 
bones and vertebrae in the rat, it did not induce major malformations in rats or rabbits. There are 
no studies of dabigatran etexilate in pregnant women and therefore, the potential risk in these 
patients is unknown. There are no clinical data available on the excretion of dabigatran into 
breast milk.6 
In light of these data, only male and non-pregnant, non-lactating female participants will be 
enrolled in this study. Sexually active female subjects of childbearing potential and 
non-surgically sterile male participants with female partners of childbearing potential will be 
required to use a double contraceptive method. Pregnancy tests will also be performed at 
different times over the course of the study for female participants. Additional pregnancy 
reporting information is provided in section 8.4.7. 
Additionally, most older subjects demonstrate an increase in dabigatran exposure; especially in 
those patients with age-related decline of renal function. Elderly subjects showed an increase of 
40 to 60% (1.4 to 1.6-fold) in the AUC and about 25% (1.3-fold) in Cmax, compared to young 
subjects.6 Therefore, the population in this study will include healthy individuals between the 
ages of 18 and 55 years. 
Finally, for patients of low body weight (< 50 kg), dabigatran etexilate is to be used with caution 
since limited data are available in these patients. As such, a lower limit of 50 kg will be applied 
to participants in this study . 
1.7 
Benefit/Risk Assessment 
The inclusion and exclusion criteria have been chosen to select participants who are known to be 
free from any significant illness, history of autoimmune diseases, and from any condition that 


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could impact their safety or interfere with meeting the study objectives. The proposed safety 
screening and monitoring assessments are deemed to be sufficient to monitor potential risks of 
camlipixant administration alone and in combination with gemfibrozil or dabigatran etexilate. 
There is no anticipated therapeutic benefit for the healthy participants in this study. 


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2. 
Objectives 
Primary objectives: 
• To assess the effect of repeated oral doses of gemfibrozil, a CYP2C8 inhibitor, on the PK 
of a single oral dose of camlipixant (Part 1) administered to healthy participants. 
• To assess the effect of repeated oral doses of camlipixant on the PK of a single oral dose 
of dabigatran etexilate, a P-gp substrate (Part 2), administered to healthy participants. 
Secondary objective: 
• To evaluate the safety and tolerability of camlipixant when administered alone and in 
combination with gemfibrozil or dabigatran etexilate to healthy participants. 
3. 
Endpoints 
Primary endpoints: 
• PK parameters: AUC0-inf, AUC0-t, and Cmax of camlipixant (Part 1) and dabigatran 
(Part 2*) 
Secondary endpoints: 
• PK parameters: Tmax, T½ el, Residual area, Kel, Cl/F, and Vz/F of camlipixant (Part 1) and 
dabigatran (Part 2*) 
*For Part 2, both total and free dabigatran will be assayed, and their PK parameters 
generated. 
• Safety evaluation: 
o AEs, SAEs, AEMIs, vital signs measurements (blood pressure, heart rate, respiratory 
rate, and oral temperature), 12-lead ECG recordings, physical examinations, and 
clinical laboratory test results, including hematology, biochemistry, coagulation, and 
urinalysis. 
4. 
Study Design 
This is a single-center, 2-part, Phase 1, open-label, fixed-sequence, DDI study designed to 
compare the PK of camlipixant when administered with and without gemfibrozil (Part 1) or to 
compare the PK of dabigatran when administered with and without camlipixant (Part 2) in 
healthy participants under fasting conditions. Participants will be enrolled to either Part 1 or 
Part 2. In each part, participants will receive the assigned treatment. The start of study conduct 
for Part 2 is independent from Part 1 study conduct. 
A total of 36 participants will be enrolled in Part 1 or Part 2 (16 participants in Part 1 and 
20 participants in Part 2). In each part, participants will receive the assigned treatment. 


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In Part 1, participants will receive a single oral dose of 1 x 50 mg camlipixant tablet on Day 1, 
followed by 72 hours of PK and safety assessments. Repeated oral doses of 
 mg 
gemfibrozil tablet will be administered 
 mg) on 
Days 5 to 11, with co-administration of a single oral dose of 1 x 50 mg camlipixant tablet with 
the morning dose of gemfibrozil on Day 9. Administration of camlipixant on Day 9 will occur 
1 hour (± 2 minutes) after administration of gemfibrozil, followed by 72 hours of PK and safety 
assessments. The study design is presented in Figure 1. 
Figure 1. Study Design Diagram for Part 1 
 
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In Part 2, participants will receive a single oral dose of
 mg dabigatran etexilate capsule 
on Day 1, followed by 72 hours of PK and safety assessments. Repeated oral doses of 1 x 50 mg 
camlipixant tablet will be administered on Days 5 to 10 (
 
mg, on Days 5 to 9), with same time co-administration of a single oral dose of 
 mg 
dabigatran etexilate capsule and the dose of camlipixant in the morning of Day 10. This will be 
followed by 72 hours of PK and safety assessments. The study design is presented in Figure 2. 
Figure 2. Study Design Diagram for Part 2 
 
The study will include a screening visit from Day -28 to Day -1. In each part of the study, 
eligible participants will be admitted to the clinical site on Day -1 and will be confined until 
completion of the assessments on Day 12 (Part 1) or Day 13 (Part 2). There will be a washout 
period of at least 4 days between the first dose of camlipixant on Day 1 and the first dose of 
gemfibrozil on Day 5 (Part 1), and a washout period of at least 4 days between the first dose of 
dabigatran etexilate on Day 1 and the first dose of camlipixant on Day 5 (Part 2). A follow-up 
phone call will be performed 7 ± 2 days after discharge (Day 19 ± 2 in Part 1 and Day 20 ± 2 in 
Part 2). 
Outings may be permitted during confinement. If permitted, outings will be supervised at all 
times by the clinical site staff to ensure compliance with the protocol and will be limited to the 
grounds surrounding the clinic. 
The total duration of study participation for each participant from screening through the 
follow-up phone call is anticipated to be approximately 7 weeks for both study parts. 
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Each study part is intended to dose in one group; if, for any reason, the study is dosed in more 
than one group, all groups will be dosed at the same clinical site and the same protocol 
requirements and procedures will be followed within each group. 
5. 
Study Population 
5.1 
Number of Participants 
It is planned to enroll up to 16 participants in Part 1 and up to 20 participants in Part 2 for 
participation in this study (total of 36 participants) in order to have an adequate number of 
participants to characterize PK in both Part 1 and Part 2. No formal sample size calculation has 
been made. Based on experience from previous similar studies, a total of 36 participants (16 in 
Part 1 and 20 in Part 2) is considered sufficient to adequately characterize the potential for a 
clinical DDI. 
5.2 
Inclusion Criteria 
Participants must meet all of the following criteria to be included in the study: 
1. Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to 
screening), ≥18 and ≤55 years of age, with BMI >18.5 and <30.0 kg/m2 and body weight 
≥50.0 kg. 
2. Healthy as defined by: 
a. the absence of clinically significant illness and surgery within 4 weeks prior to dosing. 
b. the absence of clinically significant history of neurological, endocrine, cardiovascular, 
respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, 
and metabolic disease. 
3. Female participants of non-childbearing potential must be: 
a. post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with 
confirmation by documented FSH levels ≥40 mIU/mL; or 
b. surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) at 
least 3 months prior to dosing. 
4. Females of childbearing potential who are sexually active with a non-sterile male partner 
(sterile male partners are defined as men vasectomized since at least 3 months) must be 
willing to use one of the following acceptable contraceptive methods throughout the study 
and for 90 days after the last study drug administration: 
a. simultaneous use of intra-uterine contraceptive device without hormone release system 
placed at least 4 weeks prior to study drug administration, and condom for the male 
partner; 
b. simultaneous use of diaphragm or cervical cap with intravaginally applied spermicide and 
male condom for the male partner, started at least 21 days prior to study drug 
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c. tubal ligation at least 3 months prior to dosing. 
5. Female participants must be willing not to donate ova for 90 days after the last dose. 
6. Male participants who are not vasectomized for at least 3 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 the first dose and for 90 days after the 
last dose: 
a. simultaneous use of condom and hormonal contraceptive (e.g., oral, patch, depot 
injection, implant, vaginal ring, intrauterine device) or non-hormonal intrauterine device 
used for at least 4 weeks prior to sexual intercourse for the female partner; 
b. simultaneous use of condom and a diaphragm or cervical cap with spermicide for the 
female partner. 
7. Male participants (including men who have had a vasectomy) with a pregnant partner must 
agree to use a condom from the first dose and for 90 days after the last dose. 
8. Male participants must be willing not to donate sperm for 90 days after the last dose. 
9. Able to understand the study procedures and provide signed informed consent to participate 
in the study. 
5.3 
Exclusion Criteria 
Participants to whom any of the following applies will be excluded from the study: 
1. Any clinically significant abnormal finding at physical examination at screening. 
2. Clinically significant abnormal laboratory test results or positive serology test results for 
HBsAg, HCV antibody, or HIV antigen and antibody, at screening. 
3. Any of the following laboratory parameters above the ULN values at screening or baseline 
(Day -1): AST, ALT, direct bilirubin, indirect bilirubin, and total bilirubin. Only abnormal 
values up to 1.5x ULN may be repeated once for confirmation to below ULN. 
4. Positive pregnancy test or lactating female participant. 
5. Positive urine drug screen, urine cotinine test, or alcohol breath test. 
6. Positive test for COVID-19 at admission. 
7. Known allergic reactions or hypersensitivity to camlipixant, gemfibrozil (participants in 
Part 1 only), dabigatran etexilate or dabigatran (participants in Part 2 only), or other related 
drugs, or to any excipient in the formulation. 
8. Clinically significant ECG abnormalities (for example, QTcF > 450 ms) or vital signs 
abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood 
pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at 
screening. 
9. History of drug abuse within 1 year prior to screening or use of drugs (such as cocaine, PCP, 
crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months 


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prior to screening, except for cannabis, hashish, or any products containing either, which are 
not allowed within 1 month prior to screening. 
10. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 
6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol 
per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 
40%). 
11. History of gastrointestinal disorders, such as stomach ulcers, IBS, ulcerative or 
pseudomembranous colitis, intestinal obstruction, previous liver disease or hepatic 
dysfunction (including primary biliary cirrhosis), hyperbilirubinemia, jaundice, or elevated 
liver enzymes. 
12. Known Gilbert, Rotor, Crigler-Najjar, or Dubin-Johnson syndrome. 
13. 
 
.  
14. History of gallbladder disease, including cholelithiasis. 
15. History of renal dysfunction and those with estimated CrCl less than 60 mL/min. 
16. Participants in Part 1 only: History of myoglobinuria, myopathy, myalgia, myositis or 
rhabdomyolysis. 
17. Participants in Part 1 only: History of Type I hyperlipoproteinemia. 
18. Participants in Part 2 only: Participants with haemorrhagic manifestations, clinically 
significant active bleeding, including gastrointestinal bleeding, bleeding diathesis, 
spontaneous or pharmacological impairment of haemostasis. 
19. Participants in Part 2 only: Participants with lesions, diseases, or procedures at risk of 
clinically significant bleeding/haemorrhagic risks, such as congenital or acquired 
coagulations disorders, thrombocytopenia or functional platelet defects, recent cerebral 
infarction (haemorrhagic or ischemic) within the last 6 months, active ulcerative 
gastrointestinal disease (including peptic ulcer) with recent gastrointestinal bleeding, 
bacterial endocarditis, recent biopsy or major trauma, brain, spinal or ophthalmic surgery, 
prosthetic heart valves, or hemodynamically significant rheumatic heart disease. 
20. Participants in Part 2 only: History of antiphospholipid disease. 
21. Participants in Part 2 only: Participants having undergone any major surgery within 6 months 
prior to the start of the study, unless deemed otherwise by the Investigator. 
22. Participants in Part 2 only: Any of the following laboratory parameters outside the normal 
ranges at screening or baseline (Day -1): PT and aPTT. 
23. Use of medications for the timeframes specified below, with the exception of medications 
exempted by the Investigator on a case-by-case basis because they are judged unlikely to 
affect the PK profile of the study drug or participant safety (e.g., topical drug products 
without significant systemic absorption): 
a. depot injection or implant within 3 months prior to dosing; 
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b. any drug known to induce or inhibit hepatic drug metabolism, including St. John’s wort, 
within 30 days prior to dosing or 10 half-lives, whichever is longer; 
c. prescription medications within 14 days prior to dosing; 
d. any vaccine, including COVID-19 vaccine, within 14 days prior to dosing; 
e. OTC medications and natural health products (including herbal remedies, homeopathic 
and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino 
acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to 
dosing, with the exception of the occasional use of acetaminophen (up to 2 g daily). 
24. Participation in a clinical research study involving the administration of an investigational or 
marketed drug or device within 30 days prior to dosing, administration of a biological 
product in the context of a clinical research study within 90 days prior to dosing, or 
concomitant participation in an investigational study involving no drug or device 
administration. 
25. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of 
whole blood within 8 weeks prior to dosing. 
26. Any reason which, in the opinion of the Investigator, would prevent the participant from 
participating in the study. 
5.4 
Participant Withdrawal and Replacement 
Participants will be advised that they are free to withdraw from the study at any time. Over the 
course of the study, the Sponsor and the Investigator or designee may withdraw any participant 
from the study for one of the reasons described below; participant withdrawal will be done in 
accordance with the clinical site’s SOP: 
• Safety reason; 
• Non-compliance with protocol requirements; 
• Significant protocol deviation; 
• Positive pregnancy test, drug screen, cotinine test, or alcohol breath test. 
Participants who withdraw or are withdrawn from the study after dosing will not be replaced. 
However, in the event that the number of drop-outs exceeds initial expectations, participants who 
withdraw or are withdrawn might be replaced at the discretion of the Sponsor. Such replacement 
resulting in dosing more participants than planned in this protocol would be documented in a 
protocol amendment. 
Participants who withdraw or are withdrawn will be asked to remain at the clinic until the 
Investigator or designee agrees that the participant is safe and can be discharged. As soon as 
participant withdrawal is confirmed, blood sampling will be stopped. A PK blood sample may be 
collected at the time of withdrawal if deemed required by the Investigator. Discharge/ET 
procedures will be performed at the time of withdrawal from the study or as soon as possible 
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6. 
Study Treatments 
6.1 
Drug Supplies and Accountability 
It is the responsibility of the Sponsor to ensure that study drug provided for this study are 
manufactured under Good Manufacturing Practice (GMP) and are suitable for human use. The 
Sponsor is responsible to ship a sufficient amount of dosage units to allow the clinical site to 
maintain an appropriate sampling for the study. 
The clinical site will be responsible for sourcing gemfibrozil and dabigatran etexilate from the 
Canadian market. 
The study drugs will be stored at the clinical site pharmacy as per applicable requirements in a 
locked, environmentally-controlled medication room with restricted access. Container(s) will be 
labeled according to applicable regulations. 
Individual doses for each participant will be dispensed at the clinical site pharmacy, as per 
appropriate SOP and according to the fixed-sequence, in appropriate containers indicated with at 
least the project number and the participant number/spare number. 
All study drugs received at the site will be inventoried and accounted for throughout the study 
and the result recorded in the drug accountability record according to the clinical site appropriate 
SOP. 
6.2 
Identification of Treatments 
Parts 1 and 2: 
 
 
 
. 
Part 1: 
 mg tablet of gemfibrozil (Sourced from the Canadian market) 
administered 
 mg) for 7 consecutive 
days from Day 5 to Day 11. Administration will occur before the 
 
, except for the morning dose on Day 9. 
Part 2: 
 mg 
 of dabigatran etexilate (Sourced from the Canadian market) 
administered under 
 in the morning on Day 1 and Day 10. 
6.3 
Randomization and Blinding 
This study will be an open-label study due to the objective nature of the data. Thus, no 
randomization and blinding measures will be applied. Participants will be administered each 
treatment according to the fixed-sequence scheme. 
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6.4 
Study Drug Administration 
Part 1: 
On Day 1 and Day 9, camlipixant will be administered to each participant with 240 mL of water. 
On Day 9, camlipixant will be administered 1 hour after administration of gemfibrozil dosing, 
with a time-tolerance window of ± 2 minutes. The time of administration of both camlipixant and 
gemfibrozil will be recorded, and the time interval between the 2 administrations must not fall 
outside of the scheduled acceptable range. 
Gemfibrozil will be administered to each participant as 1 tablet 
for 7 consecutive days, from 
Day 5 to Day 11. The tablet will be administered to each participant with 240 mL of water. 
Administration of gemfibrozil will be performed at approximately the same time on Days 5 to 
11. A time window of ± 10 minutes from the scheduled gemfibrozil dosing time will be allowed, 
as long as the 1-hour (± 2 minutes) time interval between gemfibrozil and camlipixant dosing on 
Day 9 is respected. 
A hand and mouth check will be performed to ensure consumption of the medication. 
On Day 1, no food will be allowed from at least 10 hours before camlipixant dosing until at least 
4 hours post-dose. 
On Day 9, no food will be allowed from at least 10 hours before gemfibrozil dosing until at least 
4 hours after camlipixant dosing. 
On Days 5 to 8, evening of Day 9, and Days 10 and 11, gemfibrozil will be administered 
approximately 30 minutes (±10 minutes) before a standard morning/evening meal. 
On Day 1, except for water given with camlipixant, no fluids will be allowed for 1 hour before 
dosing until 1 hour post-dose. On Day 9, except for water given with camlipixant and 
gemfibrozil dosing, no fluids will be allowed for 1 hour before gemfibrozil dosing until 1 hour 
post-dose of camlipixant. On Days 5 to 8, 10, and 11, except for water given with gemfibrozil 
dosing and meals, no fluids will be allowed for 1 hour before dosing until 30 minutes post-dose. 
Water will be provided ad libitum at all other times. 
Meals will be standardized throughout the study. 
Part 2: 
On Day 1 and Day 10, dabigatran etexilate will be administered to each participant with 240 mL 
of water. The capsule should be swallowed whole, and must not be chewed, broken, or opened. 
On Day 10, dabigatran etexilate will be co-administered at the same time with camlipixant. The 
time of administration of both camlipixant and dabigatran etexilate will be recorded. Camlipixant 
will be swallowed first, followed immediately by dabigatran. The entire procedure should be 
completed within 2 minutes. 
Camlipixant will be administered to each participant as 1 tablet for 6 consecutive days, from 
Day 5 to Day 9 as 
, and as 
 in the morning of Day 10. The camlipixant 
tablet will be administered to each participant with 240 mL of water. Administration of 
camlipixant will be performed at approximately the same time on Days 5 to 10. A time window 
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of ± 10 minutes from the scheduled camlipixant dosing times will be allowed, as long as the 
dabigatran etexilate will be co-administered at the same time with camlipixant. 
A hand and mouth check will be performed to ensure consumption of the medication. 
On Day 1, no food will be allowed from at least 10 hours before dabigatran etexilate dosing until 
at least 4 hours post-dose. 
On Day 10, no food will be allowed from at least 10 hours before camlipixant/dabigatran 
etexilate dosing until at least 4 hours after camlipixant/dabigatran etexilate dosing. 
On Days 5 to 9: No food will be allowed from at least 2 hours before morning camlipixant 
dosing until 1-hour post-morning dose. A normo-caloric breakfast will be served at least 1 hour 
after camlipixant administration. 
On Day 1, except for water given with the dabigatran etexilate, no fluids will be allowed for 
1 hour before dosing until 1 hour post-dose. On Day 10, except for water given with 
camlipixant/dabigatran etexilate dosing, no fluids will be allowed for 1 hour before until 1-hour 
post-dose of camlipixant/dabigatran etexilate. On Days 5 to 9, except for water given with 
camlipixant dosing, no fluids will be allowed for 1 hour before dosing until 1-hour post-dose. 
Water will be provided ad libitum at all other times. 
Meals will be standardized throughout the study. 
7. 
Study Restrictions 
7.1 
Concomitant Medications 
Participants will be required to avoid receiving any vaccination (including COVID-19 vaccine) 
and using prescription medications, OTC medications, and natural health products (including 
herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as 
vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) for 
the period of time specified in exclusion criterion no. 23 and throughout the study.  
Hormonal contraception and hormone replacement therapy for female participants will not be 
allowed. 
No concomitant medications will be allowed during the study, with the exception of medications 
required for the medical management of an AE/SAE, and medications exempted by the 
Investigator on a case-by-case basis that are judged unlikely to affect the PK profile of the study 
drug or participant safety (e.g., topical drug products without significant systemic absorption). 
If vaccination is required for any reason, it must first be discussed with and exempted by the 
Investigator on a case-by-case basis to ensure that it does not compromise the PK profile of the 
study drug or the participant safety. 
Medications taken by participants before dosing will be documented as prior medications and 
medications taken by participants after dosing up to follow-up phone call will be documented as 
concomitant medications. Any prior or concomitant medication use, other than the allowed 


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medications stated above, will be reviewed and evaluated on a case-by-case basis by the 
Investigator to determine if they affect a participant’s eligibility or continued participation in the 
study, or for potential impact on the study results. 
7.2 
Drugs, Nicotine and Alcohol 
Participants will be required to abstain from: 
• Drugs of abuse from screening and throughout the study; 
• Any nicotine product from screening and throughout the study; 
• Alcohol-based products from 24 hours prior to admission until after the last PK blood 
sample collection of the study. 
7.3 
Diet 
Participants will be required to abstain from: 
• Food or beverages containing grapefruit, Seville orange, starfruit, pomegranate, 
pineapple, or pomelo from 7 days prior to first dosing until after the last PK blood sample 
collection of the study; 
• Food or beverages containing xanthine derivatives or xanthine-related compounds 
(coffee, black/green tea, chocolate) or energy drinks from 48 hours prior to first dosing 
until after the last PK blood sample collection of the study; 
• Food containing poppy seeds from 24 hours prior to admission. 
7.4 
Posture and Physical Activity 
Part 1: 
Participants will be allowed to engage in normal activity but will avoid lying down or sleeping 
for 4 hours after camlipixant administration on Day 1. On Day 9, participants will be allowed to 
engage in normal activity but will avoid lying down or sleeping for 5 hours after gemfibrozil 
morning administration. On Days 5 to 8 and Days 10 and 11, participants will be allowed to 
engage in normal activity but will avoid lying down or sleeping for 4 hours after each morning 
gemfibrozil administration. On Days 5 to 11, participants will be allowed to engage in normal 
activity but will avoid lying down or sleeping for 2 hours after each evening gemfibrozil 
administration. 
Participants will be required to refrain from strenuous exercise at least 3 days before admission 
and throughout the study. 
Part 2: 
Participants will be allowed to engage in normal activity but will avoid lying down or sleeping 
for 4 hours after dabigatran etexilate administration on Day 1. On Day 10, participants will be 


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allowed to engage in normal activity but will avoid lying down or sleeping for 4 hours after 
camlipixant/dabigatran etexilate morning administration. On Days 5 to 9, participants will be 
allowed to engage in normal activity but will avoid lying down or sleeping for 4 hours after each 
morning camlipixant administration. On Days 5 to 9, participants will be allowed to engage in 
normal activity but will avoid lying down or sleeping for 2 hours after each evening camlipixant 
administration. 
Participants will be required to refrain from strenuous exercise at least 3 days before admission 
and throughout the study. 
8. 
Study Procedures 
Participants must provide written informed consent prior to initiation of any study procedures. 
Unless otherwise specified, study procedures will be conducted in accordance with clinical site 
SOPs. From screening through the follow-up phone call, participants will undergo study 
procedures at pre-defined times as specified in Table 1. 
Schedule of Assessments for Part 1 
and Table 2. Schedule of Assessments for Part 2 and as described in sections 8.1, 8.2, and 8.3. 
Every effort will be made to schedule and perform the procedures as close to the nominal time as 
possible, giving considerations to appropriate posture conditions, practical restrictions, and other 
procedures to be performed at the same time point. 
PK blood sample collection will be performed closest to the nominal time. When vital signs 
measurement or ECG recording coincide with a blood collection, they should preferably be 
performed before the blood collection, whenever possible. Sample collections done outside the 
pre-defined time windows will not be considered as protocol deviations since actual post-dose 
sampling times will be used for PK and statistical analyses. 
8.1 
Pharmacokinetic Assessments 
8.1.1 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples for PK analysis will be collected via an intravenous catheter or by direct 
venipuncture at the time points indicated in Table 1. Schedule of Assessments for Part 1 and 
Table 2. 
Schedule of Assessments for Part 2. Applicable time windows for PK blood 
samples are defined in the tables below. 
Table 3. 
Time Windows for PK Blood Samples for Part 1 
Day 
Time point (camlipixant) 
Time point 
(gemfibrozil) 
Time window 
1 and 9 
Pre-dose 
Pre-dose (Day 9)* 
Within 30 minutes 
0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 
6 hours 
- 
±1 minute 
8, 10, 12, 15, and 18 hours 
- 
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2 and 10 
24 hours 
- 
±5 minutes 
3, 4, 11, and 12 
48 and 72 hours 
- 
±10 minutes 
5, 6, 7, and 8 
Not applicable 
Pre-dose* 
Within 30 minutes 
*morning dose only.  
Table 4. 
Time Windows for PK Blood Samples for Part 2 
Day 
Time point (dabigatran) 
Time point 
(camlipixant) 
Time window 
1 and 10 
Pre-dose 
Pre-dose (Day 10)* 
Within 30 minutes 
0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 
and 6 hours 
- 
±1 minute 
8, 10, 12, and 16 
- 
±3 minutes 
2 and 11 
24 and 36 hours 
- 
±5 minutes 
3, 4, 12, and 13 
48, 60, and 72 hours 
- 
±10 minutes 
5, 7, 8, and 9 
Not applicable 
Pre-dose* 
Within 30 minutes 
*morning dose only.  
The planned volume of blood to be collected for this study, including that collected for eligibility 
and safety purposes, should not exceed 250 mL in Part 1 and 300 mL in Part 2. Additional tests 
or blood draws could be performed, if deemed required by the Investigator or study staff. 
Procedures for collection and processing of PK blood samples will be detailed in a separate 
document. 
Plasma concentrations of the study drug will be determined using a validated analytical method. 
Details of the analytical method will be provided in a separate document. 
8.2 
Pharmacogenomic Assessments 
One blood sample for pharmacogenomic analysis will be collected upon admission on Day -1 in 
both Part 1 and Part 2. 
8.3 
Safety and Tolerability Assessments 
Part 1: 
Participants will be monitored throughout the study by the clinical staff for AEs/SAEs. On 
Day 1, the Investigator or designee will be on site for camlipixant administration and until 
4 hours post-dose. On Day 5, the Investigator or designee will be on site for gemfibrozil morning 
administration and until 4 hours post-dose. On Day 9, the Investigator or designee will be on site 
for gemfibrozil morning administration and camlipixant administration and until 4 hours 
post-dose of camlipixant. The Investigator or designee will be available on call for the remainder 
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Part 2: 
Participants will be monitored throughout the study by the clinical staff for AEs/SAEs. On 
Day 1, the Investigator or designee will be on site for dabigatran etexilate administration and 
until 4 hours post-dose. On Day 5, the Investigator or designee will be on site for camlipixant 
morning administration and until 4 hours post-dose. On Day 10, the Investigator or designee will 
be on site for camlipixant/dabigatran etexilate morning administration and until 4 hours 
post-dose. The Investigator or designee will be available on call for the remainder of the study.  
Parts 1 and 2: 
If necessary, the Investigator or designee at the clinical site or a healthcare professional in a 
nearby hospital will administer treatment for any AEs/SAEs. A crash cart or emergency bag 
containing the necessary rescue material and appropriate medications will be available in the 
clinic to allow rapid intervention in case of emergency. 
Safety parameters (ECG, vital signs, and clinical laboratory results) will be assessed by the 
Investigator or designee, using the clinical site acceptance ranges as suggested guidelines in 
making the medical assessment. 
For eligibility purposes, abnormal vital signs measurements or clinical laboratory test results 
may be repeated once if an abnormal result is observed at the initial reading. Only abnormal 
values up to 1.5x ULN may be repeated once for confirmation to below ULN for AST, ALT, 
direct bilirubin, indirect bilirubin, and total bilirubin at screening and baseline (Day -1). 
Moreover, abnormalities found in the ECG may need to be confirmed by repeated 
measurements. In the event that the participation of a participant in the study is delayed and 
some screening procedures had been performed outside of the prescribed screening window, 
outdated screening procedures can be repeated. 
Safety assessments scheduled during the study will be repeated according to the clinical site 
SOPs or upon request from the Investigator or designee. Any abnormal repeated measurement 
will be evaluated and repeated, if judged necessary. Further action may be taken upon the 
Investigator or designee’s request. 
8.3.1 
Physical Examination 
Physical examinations will be performed at the times specified in Table 1. Schedule of 
Assessments for Part 1 and Table 2. Schedule of Assessments for Part 2. 
A complete physical examination will include assessments of the following: head, eyes, ears, 
nose, throat (HEENT), neck, chest, lungs, abdomen, musculoskeletal, dermatological, 
cardiovascular/peripheral vascular, and general neurological examination. 
A brief physical examination will include assessments of the following: HEENT, chest, lungs, 
abdomen, dermatological, cardiovascular/peripheral vascular, and areas of note elicited from the 
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8.3.2 
Body Measurements 
Body measurements will be performed at screening and will include body weight and height 
measurements, as well as BMI calculation. 
8.3.3 
Vital Signs 
Blood pressure, heart rate, respiratory rate, and oral temperature will be measured after the 
participants have been resting for at least 5 minutes in a sitting position at the times specified in 
Table 1. 
Schedule of Assessments for Part 1 and Table 2. 
Schedule of Assessments for 
Part 2. 
8.3.4 
12-lead ECG 
Standard 12-lead ECG will be recorded after the participants have been resting for at least 
5 minutes in a semi-recumbent or supine position at the times specified in Table 1.
 
Schedule of Assessments for Part 1 and Table 2. 
Schedule of Assessments for Part 2.  
8.3.5 
Laboratory Assessments 
Blood and urine samples for clinical laboratory assessments will be collected according to the 
clinical site SOPs at the times specified in Table 1. Schedule of Assessments for Part 1 and 
Table 2. 
Schedule of Assessments for Part 2. The clinical laboratory assessments to be 
performed are listed in the table below. Clinical laboratory test results may be repeated once for 
eligibility purposes as described per Section 8.3. In case of abnormal results during the conduct 
of the study, additional testing may be performed at the discretion of the Investigator. 
Table 5. 
Clinical Laboratory Assessments 
Biochemistry 
Hematology 
Urinalysis 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
GGT 
Glucose 
Phosphorus 
Potassium  
Sodium 
Total, direct and indirect bilirubin1 
Total protein 
Urea (BUN) 
Uric acid 
Hematocrit 
Hemoglobin 
Platelet count 
RBC count 
WBC count and differential: 
• 
Basophils 
• 
Eosinophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Neutrophils 
Bilirubin 
Blood (occult) 
Color and appearance 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination (in the 
event of abnormal findings) 
Coagulation2 


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Creatinine clearance (estimated 
with serum creatinine values using 
the Cockcroft-Gault)  
aPTT 
PT 
INR 
Serology 
Drug, cotinine, and alcohol 
screens 
Hormone panel - females only 
HBsAg 
HCV antibody 
HIV antigen/antibody 
 
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine 
MDMA 
Methadone 
Opiates 
PCP 
THC 
 
Urine cotinine test 
Alcohol breath test 
FSH (post-menopausal females 
only) 
Serum pregnancy test 
Urine pregnancy test 
Abbreviations: ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl 
transferase; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; 
INR = international normalized ratio; LFT = liver function test; MDMA = 3,4- methylenedioxymethamphetamine; 
PCP = phencyclidine; PT = prothrombin time; RBC = red blood cell; THC = tetrahydrocannabinol; WBC = white 
blood cell. 
1 
Considering that indirect bilirubin is calculated from total and direct bilirubin values, indirect bilirubin result 
would not be available in case of total or direct bilirubin below the limit of quantification. 
2 
If the coagulation tests results come back normal but the LFTs results are still abnormal after the repeat, the 
coagulation tests may be repeated upon Investigator’s judgement. 
8.3.6 
Follow-up Phone Call 
A follow-up phone call will be performed at the times specified in Table 1.Schedule of 
Assessments for Part 1 and Table 2. Schedule of Assessments for Part 2, to ensure the ongoing 
wellbeing of participants after discharge. 
8.4 
Adverse Events and Serious Adverse Events 
8.4.1 
Definition of Adverse Event 
An AE is defined as any untoward medical occurrence in a participant who is administered a 
pharmaceutical product and which does not necessarily have a causal relationship with the 
treatment. An AE can, therefore, be any unfavourable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not considered related to the medicinal 
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8.4.2 
Definition of Adverse Events of Medical Interest 
AEMIs are AEs of scientific interest specific to the drug class. They are required to be monitored 
closely and reported by the Investigator to the Sponsor promptly, regardless of relationship, 
severity, expectedness, and seriousness.  
AEMIs for this study include the following, but not limited to: 
• 
 
• 
 
• 
 
The incidence of AEMIs from Day 1 to Day 5 pre-dose of gemfibrozil (Part 1) will act as a 
baseline. In Part 2, AEs occurring before camlipixant dosing on Day 5 should not be 
reported/treated as AEMIs. 
AEMIs appearing following gemfibrozil administration alone from Day 5 to Day 9 pre-dose of 
camlipixant (Part 1) will be accounted for causality based on their onset date/time with respect to 
camlipixant and gemfibrozil dosing and the known safety profiles of the drugs administered in 
respective treatment periods. 
AEMIs appearing following camlipixant administration alone from Day 5 to Day 10 pre-dose of 
dabigatran (Part 2) will be accounted for causality based on their onset date/time with respect to 
camlipixant and dabigatran dosing and the known safety profiles of the drugs administered in the 
respective treatment periods.   
AEMIs appearing following camlipixant co-administration with gemfibrozil on Day 9 (Part 1) or 
dabigatran on Day 10 (Part 2) until the end of the study will be accounted for causality based on 
their onset date/time, baseline reference, and known safety profiles of the drugs administered. 
 
 
8.4.3 
Definition of Serious Adverse Event 
A SAE is defined as any untoward medical occurrence that, at any dose: 
• Results in death; 
• Is life-threatening; 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity; 
• Is a congenital anomaly/birth defect, or; 
• Is otherwise considered to be an important medical event (IME) that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may 
require intervention to prevent one of the other outcomes listed in the definition above. 
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Medical and scientific judgement should be exercised in deciding whether an event should be 
considered as an IME. 
The Sponsor can upgrade an event at any time; downgrade is not permitted at any time.  
If a SAE occurs to a participant on this study, contact the Sponsor personnel listed in 
Section 8.4.6. 
8.4.4 
Assessment of Severity 
The severity will be described and documented using the following definitions: 
Table 6. 
Severity Scale 
Severity 
Description 
Mild 
Awareness of signs and symptoms but are easily tolerated; are of minor irritant type; 
causing no limitations of usual activities. Signs or symptoms may require minor 
action. 
Moderate 
Discomfort severe enough to cause some limitations of usual activities and may 
require action. 
Severe 
Incapacitating with inability to carry out usual activities or significantly affects 
clinical status, and requires specific action and/or medical attention. 
 
8.4.5 
Assessment of Relationship to Study Drug 
Each AE/SAE must be classified based on medical judgement and according to the following 
relationship categories: definite, probable, possible, unlikely, and not related. Causality 
assessments will need to be applied to the study drug and interacting drug the participant has 
been administered. The definitions for the relationship categories are as follows: 
Table 7. 
Relationship Categories 
Assessment 
Definition 
Definite 
A clinical event, including laboratory test abnormality, occurring in a plausible time 
relationship to drug administration and which cannot be explained by concurrent 
disease or other drugs or chemicals. The response to withdrawal of the drug 
(de-challenge) should be clinically plausible. The event must be definitive 
pharmacologically or phenomenologically using a satisfactory re-challenge (the drug 
is re-administered to determine if the same reaction occurs) procedure if necessary. 
Probable 
A clinical event, including laboratory test abnormality, occurring in a plausible time 
relationship to drug administration and which cannot be explained by concurrent 
disease or other drugs or chemicals. The response to withdrawal of the drug 
(de-challenge) should be clinically plausible. 
Possible 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to the drug administration, but which could also be explained by concurrent 
disease or other drugs or chemicals. Information on drug withdrawal may be lacking 
or unclear. 


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Unlikely 
A clinical event, including laboratory test abnormality, with a temporal relationship 
to drug administration which makes a causal relationship improbable and in which 
other drugs, chemicals or underlying disease provide plausible explanations. 
Not related 
Any event that does not meet the above criteria; there is sufficient information that 
aetiology of the event is in no relation to the study drug. 
 
8.4.6 
Event Reporting 
All safety events will be recorded and evaluated for their seriousness, severity, and relationship 
to the study drug and the interacting drug. Safety events will be collected and documented 
starting from the time of signing the informed consent form (ICF), throughout the study, and 
until the follow-up phone call.  
After the initial AE/SAE report, the Investigator is required to proactively follow up with each 
participant at all subsequent visits or contact. All events will be followed up until the resolution, 
stabilization, the event is otherwise explained, or the participant refuses to provide additional 
information (documented as lost to follow-up). 
At any point after completion of the study, if a participant experiences an SAE that is considered 
by the Investigator to be either Definite, Probable, or Possible to study drug, this needs to be 
submitted to the Sponsor as described within. 
Safety events will be reported within 24 hours of learning of the event, using the appropriate 
reporting forms (SAE Form or Pregnancy Form). The notification must be directed to: 
IQVIA Safety Operations: 
PHV_EarlyPhaseSafety_SO@iqvia.com 
 
 
 
And to: 
 
Blank copies of the forms are included in the study Investigator’s file. It is not acceptable for the 
Investigator to send photocopies of the patient’s medical records to the Sponsor company or its 
representative in lieu of completion of the appropriate AE electronic case report form (eCRF) 
page or SAE Report Form. However, there may be instances when copies of medical records for 
certain cases are requested by the Sponsor or its representative. In this instance, all participant 
identifiers will be blinded on the copies of the medical records before submission to the Sponsor 
or its representative.  
If the Investigator does not have all information regarding an SAE, he/she will not wait to 
receive additional information before completing and sending the form. 
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Follow-up reports (as many as required) should be completed and faxed/e-mailed following the 
same procedure above. The Investigator should follow the participant with the event until 
resolution or stabilization of the condition. 
The Investigator must keep a copy of all documentation related to the event in the clinical site 
files. 
8.4.6.1 
Suspected Unexpected Serious Adverse Event Reporting to the IEC and 
Regulatory Agency(ies) 
It is the responsibility of the clinical site to report suspected, unexpected, serious adverse 
reactions (SUSARs) to the IEC responsible for the study per their policies. Report of fatal or 
life-threatening SUSARs must be made as soon as possible, but no later than 7 calendar days 
after first knowledge of the event. Report of SUSARs that are neither fatal nor life-threatening 
must be made as soon as possible, but no later than 15 calendar days after first knowledge of the 
event. 
The Sponsor (or representative) is responsible for notifying the regulatory agency(ies) of 
SUSARs observed during the study conduct per their regulations, as soon as possible but no later 
than 7 calendar days after becoming aware of the information when fatal or life-threatening, or 
15 calendar days when neither fatal nor life-threatening. The Sponsor (or representative) is 
responsible to comply with any other applicable regulatory requirement(s) related to the 
reporting of SAE to other regulatory authority(ies). 
8.4.7 
Pregnancy Reporting 
In the event a dosed female participant or the female partner of a dosed male participant (i.e., has 
received at least one dose of the investigational product) becomes pregnant during or up to 
30 days after the last dose, this pregnancy will be reported to the Sponsor (or representative) 
within 24 hours of first knowledge of the event as described in Section 8.4.6. The applicable 
Pregnancy Notification and Outcome forms will be used.  
Any participant who becomes pregnant during the study will be immediately withdrawn. 
Follow-up information regarding the course and outcome of the pregnancy will be documented 
(after obtaining the consent of the female partner) as per site’s SOP.  
If at any time during the pregnancy or the outcome of the pregnancy, the participant and/or baby 
experiences an AE that meets the criteria of an SAE and/or reportable event, reporting of the 
event to the IEC responsible for the study and/or to applicable regulatory agency(ies) will be 
performed as per site’s SOP and country-specific reporting requirement. 
8.4.8 
Overdose Reporting 
Although unlikely to occur as study drug is administered as a single dose under direct 
supervision, should a participant experience an overdose (with or without an AE/SAE), protocol 
deviation will need to be documented and reported promptly to the Sponsor. 


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8.5 
Premature Termination of the Study 
The study may be prematurely terminated by the Investigator following consultation with the 
Sponsor, by the Sponsor or by the regulatory authorities. Following a decision to discontinue the 
trial, the Investigator will promptly inform the active study participants and the IEC responsible 
for this trial, stating the reasons for discontinuation of the study. It is the responsibility of the 
Sponsor (or representative) to report the premature termination of the study to the regulatory 
authority(ies), when required by the applicable regulatory requirement(s). 
9. 
Statistical Analyses 
A complete description of the statistical analyses to be performed on PK as well as safety and 
tolerability data will be presented in a statistical analysis plan (SAP). 
9.1 
Analysis Populations 
9.1.1 
Safety Population 
The safety population is defined as all participants who receive at least one dose of the study 
drug. 
9.1.2 
Pharmacokinetic Concentration Population 
Part 1: 
The pharmacokinetic concentration (PC) population for camlipixant will include all participants 
who received at least one dose of camlipixant drug at Day 1 or Day 9 and have at least one 
reportable concentration. 
Part 2: 
The PC population for dabigatran etexilate will include all participants who received at least one 
dose of dabigatran etexilate drug at Day 1 or Day 10 and have at least one reportable 
concentration. 
9.1.3 
Pharmacokinetic Parameter Population 
Part 1: 
The PK parameter population will include all participants for whom the Day 1 and Day 9 PK 
profiles of the victim drug camlipixant can be adequately characterized, specifically, when 
administered alone and in combination with gemfibrozil. 
Part 2: 
The PK parameter population will include all participants for whom the Day 1 and Day 10 PK 
profiles of the victim drug dabigatran can be adequately characterized, specifically, when 
administered alone and in combination with camlipixant. 


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Any participant who experienced emesis during the sampling interval will be evaluated on a 
case-by-case basis in order to determine whether the participant will be excluded from the 
descriptive statistics and statistical analysis. 
Here are some aspects to be considered (but not to be limited to) when determining data 
availability for the PK population: inclusion and exclusion criteria, acceptable times for visit 
dates and measurements, compliance with the dosing timing and number of camlipixant and 
gemfibrozil treatments (Part 1), dabigatran etexilate and camlipixant treatments (Part 2), the 
nature and quality of the data, withdrawal, and any protocol deviation. The final responsibility of 
deciding which participants are to be included or excluded lies with the Investigator and/or the 
Sponsor. 
9.1.4 
Pharmacogenomic Population 
The pharmacogenomic population is defined as all participants in the safety population who had 
at least one pharmacogenomic measurement data available. 
9.2 
Pharmacokinetic Parameters 
The following PK parameters will be calculated based on the PK population by standard 
non-compartmental methods for camlipixant (Part 1) and dabigatran (free and total) (Part 2): 
• AUC0-t: Area under the concentration-time curve from time zero until the last observed 
concentration 
• AUC0-inf: Area under the concentration-time curve from time zero to infinity 
(extrapolated) 
• Residual area: Percentage of AUC0-inf due to extrapolation from the time of the last 
observed concentration to infinity, calculated as [1 – (AUC0-t/AUC0-inf)] x 100 
• Cmax: Maximal observed concentration 
• Tmax: Time when the maximal concentration is observed 
• T½ el: Terminal elimination half-life 
• Kel: Terminal elimination rate constant 
• Cl/F: Apparent clearance 
• Vz/F: Apparent volume of distribution 
The following information will be presented for gemfibrozil (Part 1): pre-dose concentrations on 
the morning of Days 5, 6, 7, 8, and 9. 
The following information will be presented for camlipixant (Part 2): pre-dose concentrations on 
the morning of Days 5, 7, 8, 9, and 10. 
Additional PK parameters may be calculated. 
9.3 
Pharmacokinetic Statistical Analysis 
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Individual and mean plasma concentration versus time curves will be presented for both linear 
and semi-log scales. Descriptive statistics (arithmetic and geometric means, standard deviation 
[SD], coefficient of variation (CV%), minimum [Min], maximum [Max], and median) of the 
plasma concentrations versus time will be presented as well for the PK parameters. 
Part 1: 
 
 
 
 
 
 
 
 
 
Concentrations for gemfibrozil will be tabulated. They will be presented as supportive data. 
Descriptive statistics on pre-morning dose concentrations of gemfibrozil (Days 7, 8 and 9) will 
be performed to evaluate the attainment of steady-state. 
Part 2: 
 
 
 
 
 
 
 
 
 
PK parameters for free dabigatran will also be calculated as above, and presented as supportive 
data. 
Concentrations for camlipixant will be tabulated. They will be presented as supportive data. 
Descriptive statistics on pre-morning dose concentrations of camlipixant (Days 8, 9, and 10) will 
be performed to evaluate the attainment of steady-state. 
Additional PK statistical analysis may be performed. 
A SAP will be prepared after completion of the final protocol and prior to database lock. 
9.4 
Criteria for No Drug-Drug Interaction for Camlipixant 
Part 1: 
 
. 
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Part 2: 
 
 
9.5 
Safety and Tolerability Analysis 
Demographic parameters will be summarized descriptively. 
Safety and tolerability analysis will be performed for all participants in the safety population. No 
inferential statistical analysis of safety data is planned. 
Safety and tolerability of camlipixant alone (Part 1 and Part 2) and in combination with 
gemfibrozil (Part 1) or dabigatran etexilate (Part 2) will be evaluated through the assessment of 
AEs, SAEs, AEMIs (i.e., seriousness, severity, relationship to the study drug and the interacting 
drug, outcome, duration, and management), vital signs, 12-lead ECGs, clinical laboratory tests, 
and physical examinations. AEs will be coded using the latest version of the Medical Dictionary 
for Regulatory Activities (MedDRA). 
Concomitant medications will be coded using the most current version of World Health 
Organization drug (WHODrug) dictionary available.  
Note that both MedDRA and WHODrug dictionaries are updated twice annually. 
TEAEs will be tabulated by treatment. Changes from baseline values in vital signs, 12-lead 
ECGs, and clinical laboratory tests will be evaluated. Safety and tolerability data will be reported 
using descriptive statistics. 
9.6 
Pharmacogenomic Evaluation 
One blood sample for pharmacogenomic testing will be taken on Day -1.
 
. The sample may be also used to investigate other possible exploratory markers as 
deemed necessary  
10. Data Collection 
The source data will be collected mainly on paper as per site SOPs. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Source documents will 
be maintained in order to maintain data integrity. The Investigator and/or the clinical staff have 
the responsibility of ensuring the accuracy, completeness, legibility, and timeliness of the source 
data. 
Source data will be transcribed by the clinical site in the RAVE electronic data capture system 
eCRF designed to capture study protocol required data. Vendor data will be received 
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electronically and will be reconciled with eCRF data. Details on the data management process 
will be described in a data management plan (DMP). 
11. Regulatory Considerations and Quality Assurance 
11.1 IEC Approval of Protocol and Other Study Documents 
The Investigator(s) agree to provide the IEC with all appropriate documents, including a copy of 
the protocol/amendments, ICFs, advertising text (if any), Investigator’s Brochure (if any), and 
any other written information provided to study participants. The trial will not begin until the 
Investigators have obtained the IEC favourable written approvals for the above-mentioned study 
documents. A properly executed written ICF shall be read, signed, and dated by each participant 
prior to entering the trial or prior to performing any study procedure. The original signed and 
dated ICF will be kept at the clinical site and a copy will be given to the participant. 
In the event that the protocol is amended, the revised protocol must be approved by the IEC prior 
to its implementation, unless the changes involve only logistical or administrative aspects of the 
trial. If a revised ICF is introduced during the study, each participant’s further consent must be 
obtained. The new version of the ICF must be approved by the IEC, prior to subsequently 
obtaining each participant’s consent. 
The Investigator and the Sponsor’s representative must sign the protocol and its amendments (if 
any) before initiating the study. 
It is the Sponsor’s responsibility to submit the protocol and its amendments (if any), and the 
ICFs to regulatory authorities when necessary. This task has been delegated to the contract 
research organization (CRO). 
11.2 Compliance 
This study will be conducted in compliance with the protocol, GCP ICH E6 (R2), all applicable 
regulations, including the Federal Food, Drug and Cosmetic Act, U.S. applicable Code of 
Federal Regulations (title 21), and any IEC requirements relative to clinical studies. The study 
will also be conducted in compliance with the recommendations laid down in the most recent 
version of the Declaration of Helsinki, with the exception that registration of such Phase 1 trials 
in a publicly accessible database is not mandatory. As required by the Canadian regulatory 
agency, a Clinical Trial Application (CTA) will be submitted before the beginning of the study 
and a No Objection Letter (NOL) must be received prior to dosing. 
11.3 Quality Assurance and Monitoring 
The Sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the Sponsor lies with the Investigator generating the data. When 
applicable, quality assurance procedures will be performed according to the site SOPs. 


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The study will be monitored according to the Sponsor monitoring plan and SOP to ensure that it 
is conducted and documented properly according to the protocol, GCP, and all applicable 
regulatory requirements. The Sponsor is entitled to access information about the status of the 
study and to review the original documents of the study. 
The Sponsor may arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, SOPs, GCP, and all applicable 
regulatory requirements. In such case, audits will be independent of and separate from the 
routine monitoring and quality control functions. 
11.4 Confidentiality and Retention of Study Records 
This document contains trade secrets and commercial information that is confidential and may 
not be disclosed to third parties. Persons to whom this study protocol is disclosed must be 
informed that all the information herein is confidential and may not be further divulged. These 
restrictions will apply as well to all future communications if deemed privileged or confidential. 
Publication of the study results may only be allowed with written permission from the Sponsor. 
All information on a participant obtained during the conduct of the study will be kept 
confidential. Participants will be identified by an anonymized identifier on all samples and study 
records provided to the Sponsor or designee. In compliance with ICH GCP, the Sponsor’s 
authorized representatives, monitor(s), auditor(s), IEC, and regulatory authority(ies) will be 
granted direct access to the participant’s original trial-related records for verification of clinical 
trial procedures and/or data, without violating the confidentiality of the participant, to the extent 
permitted by the applicable laws and regulations. Consent from the participant for disclosure of 
such information will be obtained in writing in the ICF. In addition, should a participant require 
medical care or hospitalization during the course of the study, the clinical site may contact the 
treating physician with the participant’s consent, except that consent may not be requested if 
there is an emergency situation. If the results of the study are published, the participant’s identity 
will remain confidential. 
The clinical site will maintain adequate study records for 25 years after completion or 
termination of study. The Sponsor will be notified prior to the destruction of study records. 


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12. References 
5 
TEVA-GEMFIBROZIL, Product Monograph. Version revised on June 29, 2015. Drug 
Product Database, Health Canada. Available online at: health-products.canada.ca/dpd-
bdpp/index-eng.jsp 
6 
PrPRADAXA®, Product Monograph. Version revised on March 23, 2020. Drug Product 
Database, Health Canada. Available online at: health-products.canada.ca/dpd-
bdpp/index-eng.jsp 
7 
Center for Drug Evaluation and Research (CDER), FDA. Guidance for Industry: Clinical 
Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter-Mediated Drug 
Interactions. January 2020. 
8 
Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. 
Content current as of 08/24/2022. Accessed on: https://www.fda.gov/drugs/drug-
interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-
and-inducers#table4-2. 
9 
Bruderer S, Petersen-Sylla M, Boehler M, Remeňová T, Halabi A, Dingemanse J. Effect 
of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active 
metabolite in healthy subjects. Br J Clin Pharmacol. 2017 Dec;83(12):2778-2788. 
10 
Itkonen MK, Tornio A, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT. Clopidogrel 
and Gemfibrozil Strongly Inhibit the CYP2C8-Dependent Formation of 3-
Hydroxydesloratadine and Increase Desloratadine Exposure In Humans. Drug Metab 
Dispos. 2019;47(4):377-385. 
11 
Härtter S, Sennewald R, Nehmiz G, Reilly P. Oral bioavailability of dabigatran etexilate 
(Pradaxa®) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 
2013;75(4):1053-1062. 
 
 
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13. Appendix 1 
Summary Table for Part 1 
 
Procedures 
Screening 
• 
Informed consent 
• 
Inclusion/exclusion criteria 
• 
Demographic data 
• 
Medical and medication history 
• 
Complete physical examination 
• 
Body measurements (height, weight, BMI) 
• 
Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature) 
• 
12-lead ECG 
• 
Serology (HBsAg, HCV antibody, and HIV antigen and antibody) 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Drug, cotinine, and alcohol screens 
• 
Urine pregnancy test 
• 
FSH levels to confirm post-menopausal status 
• 
Monitoring of AE/SAE/AEMI 
D -1 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Start of confinement 
• 
Blood sample for pharmacogenomic analysis 
• 
Brief physical exam 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Drug, cotinine, and alcohol screens 
• 
COVID-19 test 
• 
Serum pregnancy test 
D1 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Single dose administration of camlipixant 50 mg tablet 
• 
Blood samples for PK analysis of camlipixant 
• 
Blood pressure and heart rate: before dosing 
• 
12-lead ECG: before dosing 
D2 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of camlipixant 
D3 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of camlipixant 
D4 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
COVID-19 test 
• 
Blood samples for PK analysis of camlipixant 
D5 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
mg tablet 
 
• 
Blood sample for PK analysis of gemfibrozil 
• 
12-lead ECG: pre-dose of gemfibrozil administration 
• 
Biochemistry (including LFT and CK), hematology, coagulation, and urinalysis: before dosing 
D6 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
mg tablet 
 
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• 
Blood sample for PK analysis of gemfibrozil 
D7 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
mg tablet 
 
• 
Blood sample for PK analysis of gemfibrozil 
D8 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
 mg tablet 
 
• 
Blood sample for PK analysis of gemfibrozil 
• 
Brief physical exam in the evening 
D9 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
 mg tablet 
 
• 
Single dose administration of camlipixant 50 mg tablet 1 hour (± 2 minutes) after gemfibrozil 
morning administration 
• 
Blood samples for PK analysis of camlipixant 
• 
Blood sample for PK analysis of gemfibrozil 
• 
Blood pressure and heart rate: before gemfibrozil dosing 
• 
12-lead ECG: before gemfibrozil dosing and approximately 1 hour post-dosing of camlipixant 
• 
Biochemistry (including LFT and CK), hematology, coagulation and urinalysis before 
gemfibrozil dosing 
D10 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
mg tablet 
 
• 
Blood samples for PK analysis of camlipixant 
D11 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of gemfibrozil 
mg tablet
 
• 
Blood samples for PK analysis of camlipixant 
D12 
Discharge or 
ET 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Brief physical exam 
• 
Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature) 
• 
12-lead ECG 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Urine pregnancy test 
• 
Blood samples for PK analysis of camlipixant 
• 
Discharge 
D19 ± 2 
• 
Follow-up phone call 
• 
Monitoring of AEs/SAEs/AEMIs and concomitant medications 
Abbreviations: AE = adverse event; AEMI = adverse event of medical interest; 
; BMI = body mass 
index; CK = creatine kinase; COVID-19 = coronavirus 2019; ECG = electrocardiogram; ET = early termination; 
FSH = follicle-stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; LFT = liver function test; PK = pharmacokinetic, SAE = serious adverse event. 
 
 
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Summary Table for Part 2 
 
Procedures 
Screening 
• 
Informed consent 
• 
Inclusion/exclusion criteria 
• 
Demographic data 
• 
Medical and medication history 
• 
Complete physical examination 
• 
Body measurements (height, weight, BMI) 
• 
Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature) 
• 
12-lead ECG 
• 
Serology (HBsAg, HCV antibody, and HIV antigen and antibody) 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Drug, cotinine, and alcohol screens 
• 
Urine pregnancy test 
• 
FSH levels to confirm post-menopausal status 
• 
Monitoring of AEs/SAEs/AEMIs 
D -1 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Start of confinement 
• 
Blood sample for pharmacogenomic analysis 
• 
Brief physical exam 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Drug, cotinine, and alcohol screens 
• 
COVID-19 test 
• 
Serum pregnancy test 
D1 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Single dose administration of dabigatran etexilate 
mg capsule 
• 
Blood samples for PK analysis of dabigatran 
• 
Blood pressure and heart rate: before dosing 
• 
12-lead ECG: before dosing 
D2 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of dabigatran 
D3 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of dabigatran 
D4 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
COVID-19 test 
• 
Blood samples for PK analysis of dabigatran 
D5 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of camlipixant 50 mg tablet 
 
• 
Blood sample for PK analysis of camlipixant 
• 
12-lead ECG: pre-dose 
• 
Biochemistry (including LFT and CK), hematology, coagulation, and urinalysis: before dosing 
D6 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of camlipixant 50 mg tablet 
 
D7 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
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• 
Multiple dose administration of camlipixant 50 mg tablet 
 
• 
Blood sample for PK analysis of camlipixant 
D8 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of camlipixant 50 mg tablet 
 
• 
Blood sample for PK analysis of camlipixant 
D9 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Multiple dose administration of camlipixant 50 mg tablet 
 
• 
Blood sample for PK analysis of camlipixant 
• 
Brief physical exam in the evening 
• 
Biochemistry (including LFT and CK), hematology, coagulation and urinalysis 
D10 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Morning dose administration of camlipixant 50 mg tablet 
• 
Single dose administration of dabigatran etexilate 
 mg capsule 1 hour (± 2 minutes) after 
camlipixant administration 
• 
Blood samples for PK analysis of dabigatran 
• 
Blood sample for PK analysis of camlipixant 
• 
Blood pressure and heart rate: before camlipixant dosing 
• 
12-lead ECG: before camlipixant dosing 
D11 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of dabigatran 
D12 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Continued confinement 
• 
Blood samples for PK analysis of dabigatran 
D13 
Discharge or 
ET 
• 
Monitoring and recording of AEs/SAEs/AEMIs and concomitant medication use 
• 
Blood samples for PK analysis of dabigatran 
• 
Brief physical exam 
• 
Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature) 
• 
12-lead ECG 
• 
Biochemistry (including LFT and CK), hematology, coagulation, urinalysis 
• 
Urine pregnancy test 
• 
Discharge 
D20 ± 2 
• 
Follow-up phone call 
• 
Monitoring of AEs/SAEs/AEMIs and concomitant medications 
Abbreviations: AE = adverse event; AEMI = adverse event of medical interest; 
; BMI = body mass 
index;  CK = creatine kinase; COVID-19 = coronavirus 2019; ECG = electrocardiogram; ET = early termination; 
FSH = follicle-stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; LFT = liver function test; PK = pharmacokinetic, SAE = serious adverse event. 
 
 
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laws and therefore have been excluded.

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  221854
Official Title of Study: A PHASE 1, 2-PART, OPEN-LABEL, FIXED-
SEQUENCE STUDY EVALUATING POTENTIAL DRUG-DRUG 
INTERACTIONS BETWEEN GEMFIBROZIL (PART 1) OR 
DABIGATRAN ETEXILATE (PART 2) AND CAMLIPIXANT 
(BLU-5937) 50 mg TABLET IN HEALTHY PARTICIPANTS UNDER 
FASTING CONDITIONS
Date of Document: 27-Nov-2023 (The latest date on pg 3 is redacted as PI 
since it is a part of an individual's signature)


This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 1 of 29 
 
 
Statistical Analysis Plan for Interventional Studies (Early Phase) 
 
 
Sponsor Name: Bellus Health 
 
Protocol Number: 220265 (BUS-P1-12) 
 
Protocol Title: A Phase 1, 2-Part, Open-label, Fixed-sequence Study Evaluating the Potential 
Drug-Drug Interactions between Gemfibrozil (Part 1) or Dabigatran Etexilate (Part 2) and 
Camlipixant (BLU-5937) 50 mg Tablet in Healthy Participants under Fasting Conditions 
 
Protocol Version and Date: Final, 20-Jun-2023 
 
Sponsor Study Number: BUS-P1-12 
 
Authors: 
, Principal Biostatistician 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Bellus Health. Acceptance of this 
document constitutes agreement by the recipient that no information contained herein will be published or 
disclosed without prior written authorization from an official of Bellus Health. However, this document 
may be disclosed to the appropriate Institutional Review Board and ethics committees or duly authorized 
representatives of a national regulatory authority under the condition that they are requested to keep it 
confidential. In the event of an actual or suspected breach of this obligation, 
 should be 
notified promptly. 
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 2 of 29 
Revision History 
Version 
Date 
(DD-Mmm-YYYY) 
Document Owner 
Revision Summary 
1.0 
09-Nov-2023 
 
Final 
 
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 3 of 29 
Approvals 
I confirm that I have reviewed this document and agree with the content. 
 Approval 
, 
Principal Biostatistician 
 
Name, Title 
Lead Biostatistician  
 Signature 
 
Date 
(DD-Mmm-YYYY) 
  
Sr. Biostatistician 
 
Name, Title 
Senior Reviewing Biostatistician 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
,  
Sr. Pharmacokinieticist 
 
Name, Title 
Lead Pharmacokineticist 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
 Sr MW 
Name, Title 
Lead Medical Writer 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
Bellus Health Approval 
 Ph.D., 
 
  Head of Biostatistics 
 
Name, Title 
Sponsor Contact 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
, M.Sc., 
 Early Phase Development 
  
Name, Title 
Sponsor Contact 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
, BPharm, Ph.D., 
 of Clinical Pharmacology 
 
Name, Title 
Sponsor Contact 
 Signature 
 
Date 
(DD-Mmm-YYYY) 
 
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 4 of 29 
Table of Contents 
Revision History ..............................................................................................................................2 
Approvals .........................................................................................................................................3 
Table of Contents .............................................................................................................................4 
Glossary of Abbreviations ...............................................................................................................6 
1. 
Purpose .....................................................................................................................................8 
1.1 Responsibilities ....................................................................................................................8 
1.2 Timings of Analyses ............................................................................................................8 
2. 
Study Objectives .......................................................................................................................8 
3. 
Study Description .....................................................................................................................9 
3.1 Subject Selection .................................................................................................................9 
3.2 Determination of Sample Size .............................................................................................9 
3.3 Treatment Assignment .........................................................................................................9 
3.4 Randomization and Blinding .............................................................................................10 
3.5 Participant Withdrawal and Replacement .........................................................................10 
4. 
Endpoints ................................................................................................................................10 
5. 
Analysis Populations ..............................................................................................................11 
5.1 Safety Population ...............................................................................................................11 
5.2 Pharmacokinetic Concentration Population ......................................................................11 
5.3 Pharmacokinetic Parameter Population .............................................................................11 
5.4 Pharmacogenomic Population ...........................................................................................12 
6. 
General Aspects for Statistical Analysis .................................................................................12 
6.1 General Methods ................................................................................................................12 
6.2 Summary Statistics: ...........................................................................................................13 
6.3 Key Definitions ..................................................................................................................14 
6.4 Missing Data ......................................................................................................................14 
7. 
Study Population .....................................................................................................................15 
7.1 Subject Disposition ............................................................................................................15 
7.2 Protocol Deviations ...........................................................................................................15 
7.3 Inclusion and Exclusion Criteria .......................................................................................16 
7.4 Demographics and Other Baseline Characteristics ...........................................................16 
7.5 Medical History .................................................................................................................16 
7.6 Medications .......................................................................................................................16 
7.7 Drug, Cotinine, and Alcohol Screens ................................................................................16 
7.8 Pregnancy Screening .........................................................................................................16 
7.9 Additional Screening Tests ................................................................................................16 
8. 
Pharmacokinetic (PK) Analyses .............................................................................................17 
8.1 Data Handling ....................................................................................................................17 
8.1.1 PK Parameters Calculation Rules ...............................................................................17 
8.1.2 Data Presentation Rules ..............................................................................................18 
8.2 Pharmacokinetic (PK) Parameters .....................................................................................18 
8.3 Assessment of Gemfibrozil Effect (Part 1) ........................................................................19 
8.4 Assessment of Camlipixant Effect (Part 2) .......................................................................20 
8.5 Attainment of Steady State ................................................................................................21 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 5 of 29 
9. 
Pharmacogenomic Analyses ...................................................................................................21 
10. 
Safety...................................................................................................................................21 
10.1 Exposure ..........................................................................................................................21 
10.2 Adverse Events (AEs) .....................................................................................................21 
10.3 Laboratory Evaluations ....................................................................................................22 
10.4 Vital Signs .......................................................................................................................22 
10.5 Electrocardiograms (ECGs) .............................................................................................23 
10.6 Physical Examination ......................................................................................................23 
11. 
Changes from Analysis Planned in the Protocol .................................................................23 
12. 
Programming Considerations ..............................................................................................24 
12.1 General Considerations ....................................................................................................24 
12.2 Table, Listing, and Figure Format ...................................................................................24 
12.2.1 General ......................................................................................................................24 
12.2.2 Headers and Footers ..................................................................................................25 
12.2.3 Display Titles ............................................................................................................25 
12.2.4 Column and Row Headings ......................................................................................25 
12.2.5 Body of the Data Display ..........................................................................................25 
12.2.6 Footnotes ...................................................................................................................28 
13. 
Quality Control ...................................................................................................................28 
14. 
Reference List .....................................................................................................................29 
 
 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 6 of 29 
Glossary of Abbreviations 
Abbreviation 
Description 
AE 
adverse event 
AEMI 
adverse event of medical interest 
ANOVA 
analysis of variance 
ATC 
anatomical therapeutic chemical 
AUC 
area under the concentration-time curve 
AUC0-inf 
area under the concentration-time curve from time zero to infinity, 
extrapolated 
AUC0-t 
area under the concentration-time curve from time zero until the last 
observed concentration 
BLQ 
below the lower limit of quantification 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cl/F 
apparent clearance 
Cmax 
maximal observed concentration 
COVID-19 
coronavirus 2019 
CSR 
clinical study report 
CV 
coefficient of variation 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
Kel 
terminal elimination rate constant 
Kel Lower 
the timepoint where ln-linear Kel calculation begins 
Kel Upper 
the actual sampling time of the last measurable concentration used 
to estimate the Kel 
LLOQ 
Lower limit of quantification 
ln 
natural logarithm 
max 
maximum 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 7 of 29 
Abbreviation 
Description 
MedDRA® 
Medical Dictionary for Regulatory Activities 
min 
minimum 
N 
number of subjects 
n 
number of observations 
N/A 
not applicable 
NC 
not calculated 
NR 
no result or not reportable 
NS 
no sample 
PC 
pharmacokinetic concentration 
Pg-p 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PT 
preferred term 
p-value 
probability value 
 
 
R2 
R-squared 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOC 
system organ class 
SOP 
standard operation procedure 
T½ el 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
Tmax 
time when the maximal concentration is observed 
Vz/F 
apparent volume of distribution 
WHO DD 
World Health Organization Global Drug Dictionary 
 
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 8 of 29 
1. Purpose 
The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary 
tables, and figures which will be produced, and the statistical methodologies that will be used, are 
complete and appropriate to allow valid conclusions regarding the study objectives. 
This SAP is based on the following documents: 
• Protocol 220265 (BUS-P1-12) Final, dated 20-Jun-2023 
• Electronic case report form (eCRF) version 1.00, dated 03-Aug-2023 
The plan may change due to unforeseen circumstances; any changes made after the plan has been 
finalized will be documented. No revision to the SAP is required for changes which do not affect 
the statistical analysis methods, definitions, or rules defined in this document. If additional 
analyses are required to supplement the planned analyses described in the SAP, the changes and 
justification for the changes will be outlined in the associated clinical study report (CSR). No 
change will be made without prior written approval of the Sponsor.  
When applicable, all methodologies and related processes will be conducted according to 
 
 standard operating procedures (SOPs), as appropriate. Shells for all statistical tables, 
listings, and figures referred to in this SAP will be presented in a separate document. 
1.1 
Responsibilities 
 will perform the statistical analyses and is responsible for the production and quality 
control of all tables, figures, and listings (TFLs). 
1.2 
Timings of Analyses 
The final safety, tolerability, and pharmacokinetic (PK) analysis will be completed after all 
participants complete the final study visit or discontinue from the study. 
2. Study Objectives 
• Primary Objectives: 
o To assess the effect of repeated oral doses of gemfibrozil, cytochrome P450 (CYP) 
2C8 inhibitor, on the pharmacokinetics (PK) of a single oral dose of camlipixant 
(Part 1) administered to healthy participants. 
o To assess the effect of repeated oral doses of camlipixant on the PK of a single oral 
dose of dabigatran etexilate, a P-glycoprotein (P-gp) substrate (Part 2), 
administered to healthy participants. 
 
• Secondary Objectives: 
o To evaluate the safety and tolerability of camlipixant when administered alone and 
in combination with gemfibrozil or dabigatran etexilate to healthy participants. 
 
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 9 of 29 
3. Study Description 
This is a single-center, 2-part, Phase 1, open-label, fixed-sequence, drug-drug interaction (DDI) 
study designed to compare the PK of camlipixant when administered with and without gemfibrozil 
(Part 1) or to compare the PK of dabigatran when administered with and without camlipixant (Part 
2) in healthy participants under fasting conditions. Participants will be enrolled to either Part 1 or 
Part 2. In each part, participants will receive the assigned treatment. The start of study conduct for 
Part 2 is independent from Part 1 study conduct. 
3.1 
Subject Selection 
A total of 36 healthy male or female, non-smoking participants, ≥18 and ≤55 years of age, with 
body mass index (BMI) >18.5 and <30.0 kg/m2, and body weight ≥50.0 kg, are planned to be 
enrolled in this study. In Part 1, a total of 16 participants are to be enrolled. In Part 2, a total of 20 
participants are to be enrolled in Part 2. 
3.2 
Determination of Sample Size 
It is planned to enroll up to 16 participants in Part 1 and up to 20 participants in Part 2 for 
participation in this study (total of 36 participants) in order to have an adequate number of 
participants to characterize PK in both Part 1 and Part 2. No formal sample size calculation has 
been made. Based on experience from previous similar studies, a total of 36 participants (16 in 
Part 1 and 20 in Part 2) is considered sufficient to adequately characterize the potential for a clinical 
DDI. 
3.3 
Treatment Assignment 
In each study part, participants will receive the assigned treatment according to the fixed-sequence 
scheme described below. 
In Part 1, participants will receive a single oral dose of camlipixant on Day 1, followed by a 4-day 
washout period. Repeated oral doses of gemfibrozil will be administered
 
 on Days 5 through 11, with co-administration of a single oral dose of camlipixant with 
the morning dose of gemfibrozil on Day 9. 
 
In Part 2, participants will receive a single dose of dabigatran etexilate on Day 1, followed by a 4-
day washout period. Repeated oral doses of camlipixant will be administered 
 
on Days 5 through 9 and as 
 on Day 10, with co-administration of a single dose of dabigatran 
etexilate with the morning dose of camlipixant on Day 10.  
 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 10 of 29 
The planned dose levels and regimens are summarized in Table 3.3-1, below. 
Table 3.3-1: Treatment Regimen 
Study Part  Study Day(s) 
Treatment(s) 
Part 1 
Day 1  
1 x 50 mg camlipixant tablet 
Days 5-11 
 mg gemfibrozil tablet 
 mg) 
Day 9 
 mg gemfibrozil tablet
 mg) and  
1 x 50 mg camlipixant tablet [1 hour (± 2 minutes) after 
gemfibrozil] 
Part 2 
Day 1 
 
Days 5-10 
1 x 50 mg camlipixant tablet 
(total daily dose 100 mg) and 
 in the morning of Day 10 
Day 10 
1 x 50 mg camlipixant tablet 
  
 
 
3.4 
Randomization and Blinding 
This study will be an open-label study due to the objective nature of the data. Thus, no 
randomization and blinding measures will be applied. Participants will be administered each 
treatment according to the fixed-sequence scheme. 
3.5 
Participant Withdrawal and Replacement 
Participants will be advised that they are free to withdraw from the study at any time. Over the 
course of the study, the Sponsor and the Investigator or designee may withdraw any participant 
from the study for one of the reasons described below; participant withdrawal will be done in 
accordance with the clinical site’s SOP: 
• Safety reason; 
• Non-compliance with protocol requirements; 
• Significant protocol deviation; 
• Positive pregnancy test, drug screen, cotinine test, or alcohol breath test. 
Participants who withdraw or are withdrawn from the study after dosing will not be replaced. 
However, in the event that the number of drop-outs exceeds initial expectations, participants who 
withdraw or are withdrawn might be replaced at the discretion of the Sponsor. Such replacement 
resulting in dosing more participants than planned in this protocol would be documented in a 
protocol amendment. 
4. Endpoints 
• Primary Endpoints: 
o PK parameters: Area under the concentration-time curve from time zero to infinity, 
extrapolated (AUC0-inf), area under the concentration-time curve from time zero 
until the last observed concentration (AUC0-t), and maximal observed concentration 
(Cmax). 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 11 of 29 
• Secondary Endpoints: 
o PK parameters: Time when the maximal concentration is observed (Tmax), terminal 
elimination half-life (T½ el), residual area, terminal elimination rate constant (Kel), 
apparent clearance (Cl/F), and apparent volume of distribution (Vz/F). 
o Safety evaluation: Adverse events (AEs), serious AEs (SAEs), AEs of medical 
interest (AEMIs), vital signs measurements (blood pressure, heart rate, respiratory 
rate, and oral temperature), 12-lead electrocardiogram (ECG) recordings, physical 
examinations, and clinical laboratory test results, including hematology, 
biochemistry, coagulation, and urinalysis. 
5. Analysis Populations 
All participants’ inclusion status into each analysis population will be determined after database 
lock and before the final analysis. Participants will be analyzed according to the treatment received. 
5.1 
Safety Population 
The safety population is defined as all participants who receive at least one dose of any study drug. 
The safety population will be used for all safety and tolerability summaries and analyses. 
5.2 
Pharmacokinetic Concentration Population 
Part 1: 
The pharmacokinetic concentration (PC) population for camlipixant will include all participants 
who received at least one dose of camlipixant drug at Day 1 or Day 9 and have at least one 
reportable concentration. 
 
Part 2: 
The PC population for dabigatran etexilate will include all participants who received at least one 
dose of dabigatran etexilate drug at Day 1 or Day 10 and have at least one reportable concentration. 
 
The PC population will be used for summary and listing of concentrations. 
5.3 
Pharmacokinetic Parameter Population 
Part 1: 
The PK parameter population will include all participants for whom the Day 1 and Day 9 PK 
profiles of the victim drug camlipixant can be adequately characterized, specifically, when 
administered alone and in combination with gemfibrozil. 
 
Part 2: 
The PK parameter population will include all participants for whom the Day 1 and Day 10 PK 
profiles of the victim drug dabigatran can be adequately characterized, specifically, when 
administered alone and in combination with camlipixant.  
 
The PK parameters population will be used for all PK parameter summaries and analyses. 
 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 12 of 29 
Any participant who experienced emesis during the sampling interval will be evaluated on a case-
by-case basis in order to determine whether the participant will be excluded from the descriptive 
statistics and statistical analyses. Individual PK parameters from participant excluded from the PK 
parameter population will be presented in the listing but will be excluded from the descriptive 
statistics and statistical analyses. 
 
Here are some aspects to be considered (but not to be limited to) when determining data availability 
for the PK population: inclusion and exclusion criteria, acceptable times for study days/timepoints 
and measurements, compliance with the dosing timing and number of doses received for 
camlipixant and gemfibrozil treatments (Part 1), dabigatran etexilate and camlipixant treatments 
(Part 2), the nature and quality of the data, withdrawal, and any protocol deviation. The final 
responsibility of deciding which participants are to be included or excluded lies with the 
Investigator and/or the Sponsor. 
5.4 
Pharmacogenomic Population 
The pharmacogenomic population will include all participants in the safety population who had at 
least one pharmacogenomic measurement data available. 
6. General Aspects for Statistical Analysis 
6.1 
General Methods 
(or more recent version) will be used to perform all 
statistical analyses. All relevant data in the database will be presented in the data listings. Unless 
otherwise stated, all listings will be sorted by study part, subject number, and assessment date/time. 
All listings and summaries will be presented separately for each study part. Unless otherwise 
stated, the descriptions of the analyses which follow will apply to all study parts. 
The following labels for treatment will be used on all tabulations where the results are displayed 
by treatment, in the following order: 
• Part 1: 
o Camlipixant 
o Gemfibrozil  
o Camlipixant + Gemfibrozil 
• Part 2: 
o Dabigatran  
o Camlipixant 
o Camlipixant + Dabigatran 
For Part 1, where applicable, the treatment phases considered for the safety summaries will be: 
- 
Camlipixant alone – from Day 1 post-dose until Day 5 pre-dose of gemfibrozil; 
- 
Gemfibrozil alone – from Day 5 dosing until Day 9 pre-dose of camlipixant; 
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Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
Controlled Document ID: 2805A.00, Effective Date 29-Jul-2019 
Filing requirements: TMF 
Page 13 of 29 
- 
Gemfibrozil + Camlipixant – from camlipixant dosing on Day 9 until end of study. 
 
For Part 2, where applicable, the treatment phases considered for the safety summaries will be: 
- 
Dabigatran alone – from Day 1 post-dose until Day 5 pre-dose of camlipixant; 
- 
Camlipixant alone – from Day 5 dosing until Day 10 pre-dose of dabigatran; 
- 
Dabigatran + Camlipixant – from dabigatran dosing on Day 10 until end of study. 
6.2 
Summary Statistics: 
Unless otherwise stated, continuous variables will be summarized using the number of 
observations (n), and the statistics mean, median, standard deviation (SD), minimum (min) and 
maximum (max). The min and max values will be presented to the same number of digits as 
recorded in the eCRF, mean and median will be presented to one more significant digit than the 
raw data, and the SD will be presented to two more significant digits than the raw data. 
Summaries of change from baseline variables will include only participants who have both a 
baseline value and corresponding value at the timepoint of interest. Categorical and binary 
variables will be summarized with frequency counts and percentages. Percentages will be rounded 
to one decimal place, with the denominator being the number of participants (N) in the relevant 
population, unless otherwise stated. 
All digits will be used for PK and statistical calculations. For PK tables and listings, the final reportable 
results or data will be presented by rounding off to two decimal digits, except for the following 
situations (this applies to individual data and descriptive statistics): 
• Kel and R-squared (R2) adjusted data shall be rounded off to four decimals. 
• PK parameters related to time, such as Tmax, the timepoint where ln-linear Kel calculation 
begins (Kel Lower), and the actual sampling time of the last measurable concentration used 
to estimate the Kel (Kel Upper), must be reported with the same precision as the actual 
sampling time, rounded to three decimals. 
• Concentration versus time data, as well as Cmax shall be reported as they appear in the 
corresponding dataset. 
• Ratios and 90% CIs, intra- and inter-subject coefficients of variation (CV), and CV (%) 
will be presented to two decimal places.  
Only data from protocol scheduled (“nominal”) visits will be included in the summary tables. Data 
from unscheduled visits will not be included in the summary tables (unless they were used as 
baseline) but will be included in the listings. 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
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6.3 
Key Definitions 
Baseline: 
Unless stated otherwise, baseline will be determined for each subject and will be defined as the 
last non-missing measurement (including repeated and unscheduled assessments) obtained prior 
to the first study drug administration. Post baseline will be considered as all measurements 
collected after first study drug administration. “Unknown”, “Not Done”, “Not Applicable” and 
other classifications of missing data will not be considered when calculating baseline observations 
unless the finding is a valid categorical observation. 
Study Day: 
Study day will be calculated using first study drug administration date as the reference date. If the 
date of interest occurs on or after the first study drug administration date, study day will be 
calculated as (date of interest – first study drug administration date) + 1. If the date of interest 
occurs prior to the first study drug administration date, study day will be calculated as (date of 
interest – first study drug administration date). There will be no study Day 0. 
Prior and Concomitant Medication: 
Prior medications are defined as medications that start and stop prior to the first dose of study drug. 
All other medications will be defined as concomitant medications including those that start prior 
to the first dose of study drug and continue thereafter. Any medications with an unknown start or 
stop date will be assumed to be concomitant medications unless a partial start or stop date indicates 
otherwise. 
6.4 
Missing Data 
There will be no imputation for missing data, unless otherwise specified. Missing data shall be 
presented in subject listings as either “-” (unknown or not evaluated) or “N/A” (not applicable), 
with the corresponding definition in the footnotes. Missing descriptive statistics, or probability 
values (p-values), which cannot be estimated shall be presented as “-”. 
The listings will include the reported date/time, and the imputations rules below will be used if 
needed to classify as prior or concomitant medication, to determine if an AE is non-TEAE or 
TEAE, or to attribute to a particular treatment for the summaries. 
For inclusion in concomitant medication tables, incomplete start and stop dates on the eCRF will 
be imputed as follows: 
 
• If the start date is incomplete, the following rules will be applied: 
o Missing day: Assume the first day of the month; however, if the partial date and the 
date of first study drug administration lie within the same month and year and the 
date of first study drug administration is not after the stop date of the 
event/medication, set to the date of study drug administration. Otherwise, set to the 
stop date of the event/medication. 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
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o Missing day and month: Assume January 1st; however, if the partial date and the 
date of first study drug administration lie within the same year and the date of first 
study drug administration is not after the stop date of the event/medication, set to 
the date of first study drug administration. Otherwise, set to the stop date of the 
event/medication. 
o Missing day, month, and year: Assume date of first study drug administration if it 
is not after the stop date for the event/medication. Otherwise, set to the stop date 
for the event/medication. 
• If the stop date is incomplete, the following rules will be applied: 
o Missing day: Assume the last day of the month 
o Missing day and month: Assume the last day of the year 
o Missing day, month, and year: Assume that the event/medication is continuing 
o In the case of the death of a subject, and if the imputed end date is after the date of 
death, the end date will be imputed as the date of death. 
• If the stop date is incomplete, imputed end date will be used instead of reported end date. 
AEs without an onset date or time, or AEs with an onset date on the date of first study drug 
administration but without an onset time, will be defined as treatment-emergent, unless an 
incomplete date (e.g., month and year) clearly indicates that the event started prior to 
administration of first study drug administration, or the AE stop date indicates that the event started 
and stopped prior to the first study drug administration. 
In the case of withdrawal of consent, all data from participants who withdraw from the study will 
be included in all summaries up to the time of withdrawal. For all other withdrawals, all data 
captured will be included in the safety summaries. 
For PK analysis, only observed concentration data will be used in the data analysis except for 
concentration values below the lower limit of quantification (BLQ); see section 8.1. No attempt 
will be made to extrapolate or interpolate estimates for missing data. 
7. Study Population 
7.1 
Subject Disposition 
The number of participants who were screened, enrolled, dosed, completed the study, and 
discontinued from the study, along with reasons for discontinuation, will be summarized. The data 
will be presented by study part, treatment, and overall (frequency counts and the percentage) and 
presented by participant in a data listing. 
7.2 
Protocol Deviations 
Participant data will be examined for evidence of protocol deviations. All protocol deviations will 
be categorized (as critical, major or minor and important/non-important as per ICH E3 definition) 
and presented by participant in a data listing. 


Statistical Analysis Plan for Interventional Studies (Early Phase) 
Sponsor: Bellus Health; Protocol: 220265 (BUS-P1-12) 
 
This document is confidential. 
SAP Version: 1.0 09-Nov-2023 
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Filing requirements: TMF 
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7.3 
Inclusion and Exclusion Criteria 
All recorded inclusion and exclusion criteria status will be presented by participant in a data listing. 
Each participant’s inclusion or exclusion from each analysis population will also be presented in 
a data listing. 
7.4 
Demographics and Other Baseline Characteristics 
All demographics and baseline body measurements will be summarized by study part and 
treatment for the safety, and PC and PK parameter populations (if different from safety 
population). All demographic characteristics will be presented by participant in a data listing. 
Descriptive statistics (n, mean, SD, min, median, and max) will be calculated for continuous 
variables using the last results obtained (scheduled and unscheduled) prior to the first study drug 
administration. Frequency counts and percentages will be tabulated for categorical and binary 
variables. 
7.5 
Medical History 
Medical history will be presented by participant in a data listing. The Medical Dictionary for 
Regulatory Activities (MedDRA), Version 26.0 (or more recent version) will be used to classify 
medical history terms by system organ class (SOC) and preferred term (PT). Output data will 
include the MedDRA version used in the study. 
7.6 
Medications 
Medications taken by participants that start and stop before first dosing will be documented as 
prior medications and whereas medications taken by participants after dosing (including those that 
start prior to the first dosing and continue thereafter) up to follow-up phone call will be documented 
as concomitant medications. Prior and concomitant medications will be presented by participant 
in a data listing. The World Health Organization Global Drug Dictionary (WHO DD), Version B3, 
March 2023 (or more recent version) will be used to classify medications by anatomical 
therapeutic chemical (ATC) classification code (3rd level) and preferred name. When 3rd level 
classification code is not available, 3rd level classification will be used instead. Output data will 
include the WHO DD version used in the study. 
7.7 
Drug, Cotinine, and Alcohol Screens 
The results of urine drug, urine cotinine, and alcohol breath screen tests will be presented by 
participant in data listings. 
7.8 
Pregnancy Screening 
Pregnancy tests will be performed for all females. The follicle-stimulating hormone (FSH) level 
will be tested in postmenopausal females only. All results will be presented by participant in data 
listings. 
7.9 
Additional Screening Tests 
The results of serology tests and coronavirus 2019 (COVID-19) tests will be presented by 
participant in data listings. 


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8. Pharmacokinetic (PK) Analyses 
or more recent version) will be used for all PK 
analyses. Statistical analyses will be performed using 
. Bioanalysis of 
all samples should be completed prior to the initiation of the PK and statistical analyses. 
All PK concentration and PK parameter analyses will be conducted on the PK concentration 
population and PK parameter population, respectively. 
PK concentrations, actual times, date/time of study drug administration and sample collection will 
be listed for the PK concentration population by nominal time for each study part, study day, 
participant and treatment, and summarized for the PC population for each study part by treatment 
and timepoint, using descriptive statistics (n, number of BLQs, arithmetic and geometric means, 
SD, geometric SD, CV%, geometric mean CV%,  min, max, and median). Individual, mean (±SD) 
concentration and overlay of individual plasma concentration versus time profile will be presented 
for both linear and semi-logarithmic scales for each study part by treatment for the PC population. 
For ease of presentation, actual and nominal sampling times will be used to present results for 
individual and mean figures, respectively. 
PK parameters will be presented in data listings and summarized in tables for each study part by 
study day and treatment (or day), using descriptive statistics (n, arithmetic mean, SD, %CV, 
geometric mean, geometric SD, geometric mean CV%, minimum, median, and maximum). 
8.1 
Data Handling 
8.1.1 PK Parameters Calculation Rules 
For all PK analyses, concentration values BLQ that occur before the first measurable concentration 
of the study drug will be set to “0.00”; BLQ values that occur after first measurable concentration 
will be set to “missing”. No imputations will be made on BLQ concentrations. 
Invalid concentration values (due to bioanalytical or clinical issues) that occur prior to dosing will 
be replaced by “0.00”. Invalid concentration values that occur after dosing will be set to “missing” 
for tabulation, graphical representation, and calculation purposes. 
The actual clock time for dosing and the actual clock time for each PK sample collection will be 
recorded. For all sampling times, the actual sampling duration will be calculated as the difference 
between the sample collection actual clock time and the actual clock time of dosing. The actual 
post-dose sampling times, expressed in hours and rounded off to three decimal digits, will be used 
to calculate the PK parameters. Pre-dose sampling times will always be reported as zero (0.000), 
regardless of the time difference. Nominal sampling times will be used in concentration tables and 
mean graphs, while actual sampling times for post-dose samples will be used in the individual 
graphs. Actual sampling times for post-dose samples also will be used for PK parameter derivation, 
unless the actual sampling time is missing, in which case, the nominal time will be used. 
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8.1.2 Data Presentation Rules 
Non-measurable values reported in the plasma concentration data (i.e. values that are BLQ), will 
be entered as zero for the determination of summary statistics with the exception of geometric 
mean, geometric SD, and geometric CV%, where BLQ values will be imputed as half the lower 
limit of quantification (LLOQ) value. This also applies to any concentrations that are defined as 
PK parameters. Data recorded as “No Result” or “Not Reportable” (NR), “Not Calculated” (NC) 
or “No Sample” (NS) will be handled as missing (i.e. no assumption will be made about the actual 
concentration). 
8.2 
Pharmacokinetic (PK) Parameters 
The PK parameters shown in Table 8.2-1 below, will be calculated, whenever possible, by standard 
non-compartmental methods for camlipixant (Part 1) and dabigatran (free and total) (Part 2): 
Table 8.2-1: PK Parameters 
Parameter  Definition  
AUC0-t 
area under the concentration-time curve from time zero until the last observed 
concentration 
AUC0-inf 
area under the concentration-time curve from time zero to infinity (extrapolated) 
Cl/F 
apparent clearance, calculated as Dose/AUC0-inf 
Cmax  
maximal observed concentration 
Kel 
terminal elimination rate constant 
Residual 
area 
percentage of AUC0-inf due to extrapolation from the time of the last observed 
concentration to infinity, calculated as [1 - (AUC0-t/AUC0-inf)] x 100 
Tmax 
time when the maximal concentration is observed 
T½ el 
terminal elimination half-life, calculated as ln(2)/Kel 
Vz/F 
apparent volume of distribution, calculated as Dose/(Kel x AUC0-inf) 
Additional PK parameters may be calculated as deemed necessary. 
The following information will be presented for gemfibrozil (Part 1): pre-dose concentrations on 
the morning of Days 5, 6, 7, 8, and 9. The following information will be presented for camlipixant 
(Part 2): pre-dose concentrations on the morning of Days 5, 7, 8, 9, and 10. These data will be 
listed. Any additional PK data will be presented as appropriate. 
Note: Area under the concentration-time curve (AUC) parameters will be calculated using the 
linear up log down trapezoidal method, where the linear trapezoidal rule is used any time the 
concentration data are increasing, and the logarithmic trapezoidal rule is used any time that the 
concentration data are decreasing. 
Note: Kel will be the negative of the estimated slope of the linear regression of the ln-transformed 
plasma concentration versus time profile in the terminal elimination phase. The best fit method 
will be used to calculate the Kel from at least three concentration data points, excluding Cmax. R2 
adjusted, the goodness of fit statistic for the terminal elimination phase, adjusted for the number 
of points used in the estimation of Kel must be ≥ 0.8. If the Kel cannot be measured (e.g.: there are 
fewer than three non-zero concentrations in the terminal elimination phase), the PK parameters 
derived from Kel will be presented in listing(s) but excluded from descriptive statistics in tables.  


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All the derived parameters (i.e., AUC0-inf, T½ el, Cl/F and Vd/F) will be also flagged accordingly. 
The timepoint where ln-linear Kel calculation begins (Kel Lower), the actual sampling time of the last 
measurable concentration used to estimate the Kel (Kel Upper), and the R2 adjusted for the ln-linear 
regression for the calculation of the elimination rate constant will be reported. If the Residual area 
is greater than 20%, the individual result should be flagged in the listing, and AUC0-inf removed 
from descriptive statistics and statistical analyses.. The derived parameters (i.e., AUC0-inf, Cl/F and 
Vd/F) will be also flagged accordingly in the listing. 
Some PK parameters may not be calculated for all or some subjects, at the discretion of the 
 
pharmacokineticist if the concentration data is not deemed to be amenable to evaluation. 
Explanations for PK parameters that could not be estimated will be provided in the CSR. 
8.3 
Assessment of Gemfibrozil Effect (Part 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
  
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8.4 
Assessment of Camlipixant Effect (Part 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK parameters for free dabigatran will also be calculated as above and presented as supportive 
data. 
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8.5 
Attainment of Steady State 
As supportive data, to assess attainment of steady state, descriptive statistics on pre-dose 
concentrations of gemfibrozil in Part 1 (Days 7, 8, and 9) and camlipixant in Part 2 (Days 8, 9, and 
10) will be presented. If necessary, additional data may be presented. 
9. Pharmacogenomic Analyses 
 
 
Other possible exploratory markers may be considered as deemed necessary. If applicable, a data 
listing will be provided for the pharmacogenomic population. 
10. Safety 
Safety and tolerability analysis will be performed for all subjects in the safety population. No 
inferential statistical analysis of safety data is planned. 
10.1 Exposure 
Study drug administration will be listed by participant. 
10.2 Adverse Events (AEs) 
AEs will be coded using MedDRA, Version 26.0 (or more recent version). Output data will include 
the MedDRA version used in the study. AEs will be grouped by SOC and PT and summarized by 
actual treatment phase. The summary tables will present the number and percentage of total 
participants and number of events by SOC and by PT. 
All AE summaries will be restricted to treatment-emergent AEs (TEAEs), defined as AEs that 
commence on or after the time of first study drug administration. Any AE that first occurs pre-dose 
but worsens in severity after the first study drug administration will also be considered a TEAE. 
TEAEs will be attributed to the appropriate treatment phase as defined previously based on their 
onset date and time. TEAEs continuing after administration on the next treatment phase will be 
evaluated on a case-by-case basis (e.g: If there was no worsening in severity, it would be attributed 
to the treatment phase that coincides with the AE onset. If there was worsening in severity, it would 
be attributed to the treatment phase during which the worsening of the AE has occurred. The 
relationships could also be considered in this determination). 
The relationships for each TEAE will be evaluated separately for the two drugs administered 
during the treatment phase of respective study part and will be classified according to the study 
protocol as definite, possible, probable, unlikely or not related to respective study drugs. The 
severity of TEAEs will be classified as mild, moderate or severe. 
The number and percentage of subjects experiencing TEAEs and the number of TEAEs will be 
tabulated. Subjects who experience the same TEAE (in terms of MedDRA PT) more than once 
will only be counted once, however, the total number of events will be counted per category. This 
also applies to sub-categories (e.g.: SOC, PT) displayed in the summaries. 
The following summaries will be presented: 
• Overall summary of TEAEs 
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• TEAEs by SOC and PT 
• TEAEs by SOC, PT, and severity 
• TEAEs by SOC, PT, and relationship to each study drug 
• Serious AEs by SOC and PT 
• AEMIs by SOC and PT 
AEMIs for this study include the following, but not limited to: 
• 
 
• 
 
• 
. 
All AEs will be listed. The following listings will be included: Non-TEAEs, TEAEs, serious AEs,  
AEMIs and 
 
10.3 Laboratory Evaluations 
Laboratory data, including biochemistry, hematology, coagulation, and urinalysis, will be listed 
by participant and summarized overall separately by study day. Observed values and changes from 
baseline will be presented. 
In addition, a shift table representing the categorical change (low, normal, high) from baseline to 
each post baseline study day will be presented. 
The categorical results of urinalysis will be summarized overall as number and percentage 
separately by study day. 
Abnormal results will be flagged in the listings. 
If more than one clinical laboratory is used, a formula that takes into consideration the relative 
normal ranges of each test of the laboratories will be utilized to normalize these dataa. The 
conversion formula used for each test will depend on the typical distribution of the normal range 
for the test b. Prior to applying these formulas, units will be adjusted, as necessary. The laboratory 
which has the most results for each parameter will be considered primary in the formulas. 
10.4 Vital Signs 
Vital sign measurements will be listed by participant and summarized overall separatelyby study 
day. Observed values and changes from baseline will also be presented. 
In addition, a shift table representing the categorical change from baseline to each post baseline 
study day will be presented. 
Abnormal results will be flagged in the listings. The normal ranges as per clinical SOP (refer to 
the table below) will also be included in the listing and the summary tables. 
Vital Sign Parameters 
Normal Range (inclusive) 
Systolic blood pressure 
90 to 140 mmHg 
Diastolic blood pressure 
50 to 90 mmHg 
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Hearth rate 
50 to 100 beats/min 
Respiratory rate 
8 to 20 breaths/min 
Oral temperature 
35.8 to 37.6 ℃ 
10.5 Electrocardiograms (ECGs) 
ECG values will be listed by participant and summarized overall separately by study day. Observed 
values and changes from baseline will be presented. 
In addition, a shift table representing the categorical change in overall interpretation (normal, 
abnormal not clinically significant, or abnormal clinically significant) from baseline to each post 
baseline study day will be presented. 
Abnormal results will be flagged in the listings. The normal ranges as per clinical SOP (refer to 
the table below) will also be included in the listing and the summary tables. 
ECG Parameter 
Normal Range (inclusive) 
Hearth rate 
50 to 100 beats/min 
PR interval 
120 to 200 msec 
QRS interval 
70 to 110 msec 
QT interval 
≤ 450 msec 
QTcF interval 
≤ 450 msec 
 
10.6 Physical Examination 
The results of physical examinations will be listed by participant. Abnormal results will be flagged 
in the listings. 
11. Changes from Analysis Planned in the Protocol 
No changes were made to planned analyses. 
 
 


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12. Programming Considerations 
All TFLs and statistical analyses will be generated using
(or more 
recent version) 
 software in accordance with Food and Drug 
Administration (FDA) guidelines.
(or more recent version) 
) will be used for all PK analyses. This software was validated 
by
 in compliance with US 21 CFR Part 11 regulation. 
12.1 General Considerations 
• One 
 program can create several outputs. 
• Each output will be stored in a separate file. 
• Output files will be delivered in rich text format that can be manipulated in MS Word. 
• Numbering of TFLs will follow International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) guideline E3c. 
12.2 Table, Listing, and Figure Format 
12.2.1 General 
• TFLs will be produced in landscape format. The orientation may be changed to portrait, as 
necessary to allow additional rows to be presented. 
• TFLs will be produced using the Times New Roman font, size 9. The font size may be 
reduced as necessary to allow additional columns to be presented, but not at the expense of 
clarity. 
• The data displays for all TFLs will have a minimum blank 1-inch margin on all four sides. 
• Unless otherwise specified, TFLs will be in black and white (no color). 
• Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text, will not be used in the TFLs, unless otherwise specified. On some 
occasions, superscripts 1, 2, or 3 may be used; see below. 
• Standard keyboard characters will be used in the TFLs. Special characters, such as 
non-printable control characters, printer-specific, or font-specific characters, will not be 
used. Hexadecimal-derived characters will be used, where possible, if they are appropriate 
to help display math symbols (e.g., μ). Certain subscripts and superscripts (e.g., cm2, Cmax) 
will be employed on a case-by-case basis. 
• TFLs will be produced using sentence case, unless otherwise specified. 
 
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12.2.2 Headers and Footers 
• Times New Roman font, size 9 will be used for TFL headers and footers. 
• All outputs will have the following at the top of each page: Bellus Health  Protocol: 220265 
(BUS-P1-12). 
• All outputs will have page x of y at the top or bottom right corner of each page. TFLs are 
individually paginated in relation to total length (i.e., the page number appears sequentially 
as page x of y, where y is the total number of pages in the output). 
• The data source will be included in the footer, as applicable.  
• The date and time the output was generated will appear, along with the program name, at 
the bottom of each page. 
12.2.3 Display Titles 
Each display title includes the appropriate designation (“Table”, “Figure”, or “Listing”) and a 
numeral, along with a descriptive name (e.g., Table 14.1-1 Subject Enrollment and Disposition). 
The analysis population should also be included in each title. ICH E3 numbering is strongly 
recommended, but Sponsor preferences are obtained for final determination. Display titles are left 
aligned, single spaced, and presented in title case. A solid line spanning the margins will separate 
display titles from column headings. 
12.2.4 Column and Row Headings 
• Column and row headings are presented in title case, with the exception of complete 
sentences, which will be presented in sentence case. 
• In efficacy or pharmacokinetic tables, the variable (or characteristic) column will be on the 
far left, followed by the group columns and overall column (if applicable). P-values may 
be presented under the overall column or in separate p-value column (if applicable). 
Within-treatment comparisons may have p-values presented in a row beneath the summary 
statistics for that treatment. 
• Column and row headings will include “Unit” for numeric variables, as appropriate. 
• Column and row headings will include the number of subjects in the analysis population 
for each group, presented as (N=xx). This is different from the ‘n’ used in descriptive 
statistics, which represents the number of observations. 
• The order of treatments in the tables and listings will be placebo first, in placebo-controlled 
studies, and active comparators first, in active comparator trials, with “overall” (if 
applicable) last. 
12.2.5 Body of the Data Display 
12.2.5.1 General Conventions 
Data in columns of a table or listing are formatted as follows: 
• Alphanumeric values are left aligned. 


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• Whole numbers (e.g., counts) or numerical data are centered aligned. 
 


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12.2.5.2 Table Conventions 
• Units will be included, where available. 
• If the categories of a parameter are ordered, all categories between the maximum and 
minimum category are presented in the table, even if n=0 for all groups in a category 
between the minimum and maximum level for that parameter. See the example for the 
frequency distribution for symptom severity below. If percentages are presented in these 
tables, 0% will not be presented, therefore, counts of zero will be presented as “0”, not “0 
(0%)”. 
Severity Rating N 
Severe 
0 
Moderate 
8 
Mild 
3 
• Where the categories are not ordered (e.g., Reason for Discontinuation), only those 
categories for which there is at least one subject represented will be included. 
• An “Unknown” or “Missing” category will be added to each parameter for which 
information is unavailable for one or more subjects. 
• P-values are presented in the format: 0.xxxx, where xxxx is the value. If the p-value is less 
than 0.0001, it will be presented as “<0.0001.” If the p-value is >0.999, it will be presented 
as “>0.999.” 
• Percentage values are presented in parentheses with no spaces, one space after the count 
[e.g., 7 (12.8%), 13 (5.4%)]. Unless otherwise noted, for all percentages, the denominator 
will be the number of subjects in the analysis population for the group that has an 
observation. Percentages after zero counts are not displayed, and percentages equating to 
100% are presented as “100%” (without decimal places). 
• Unless otherwise noted, tabular displays of data for medical history, prior/concomitant 
medications, and AEs data are presented in alphabetical order. 
• The percentage of subjects is typically calculated as a proportion of the number of subjects 
assessed in the relevant group (or overall) for the analysis population presented; however, 
careful consideration is required in many instances, due to the complicated nature of 
selecting the denominator. Details of this will be presented in footnotes or programming 
notes. 
• In categorical summaries where a subject can be included in more than one category, a 
footnote or programming note will specify whether the subject is included in the summary 
statistics for all relevant categories or just one category and the criteria for selecting the 
category. 
• Where a category with a subheading (such as SOC) must be split over more than one page, 
present the subheading followed by “(cont.)” at the top of each subsequent page. The 
overall summary statistics for the subheading will only be presented on the first relevant 
page. 
 


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12.2.5.3 Listing Conventions 
• Unless otherwise noted, listings will be sorted for presentation in order of subject number, 
visit/collection day, visit/collection time, and parameter (alphabetic order). 
• Dates are printed in 
 (e.g., “ddMMMyyyy”: 01JUL2000). Missing 
portions of dates are represented on subject listings as dashes (e.g.,--JUL2000). Dates that 
are missing because they are not applicable for the subject are presented as “N/A”, unless 
otherwise specified. 
• All observed time values are presented using a 24-hour clock HH:MM:SS or HH:MM 
format (e.g., 11:26:45, or 11:26). Time will only be reported if it was measured as part of 
the study. 
• Units will be included, where available. 
12.2.5.4 Figure Conventions 
• For safety figures, study visits will be displayed on the X-axis and endpoint (e.g., treatment 
mean change from baseline) values will be displayed on the Y-axis, unless otherwise 
specified. 
• Legends will be used for all figures with more than one variable, group, or item displayed. 
• Units will be included, where available. 
12.2.6 Footnotes 
• A solid line spanning the margins will separate the body of the data display from the 
footnotes. 
• All footnotes will be left aligned, with single spacing, immediately below the solid line 
beneath the data display. 
• Informational footnotes begin with “Note:”. Reference footnotes begin with a reference 
number or letter (e.g., 1, 2, 3 or a, b, c). 
• Each new footnote starts on a new line, where possible. 
• Subject-specific footnotes are avoided, where possible. 
• Footnotes will be used sparingly and add value to the table, figure, or data listing. If more 
than six lines of footnotes are planned, a cover page may be used to display footnotes, and 
only those essential to comprehension of the data will be repeated on each page. 
13. Quality Control 
programs are developed to produce outputs such as analysis data sets, summary tables, data 
listings, figures, and statistical analyses. These are developed and undergo quality control in 
accordance with the latest versions of SOP 2800d and SOP 2801e. 
 
 
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14. Reference List 
 
aChuang-Stein, C., PhD, Research Support Biostatistics Unit, 9164–32–2, The Upjohn Company, 
Kalamazoo, Michigan. (1992). Summarizing Laboratory Data with Different Reference Ranges in 
Multi-Center 
Clinical 
Trials. 
Drug 
Information 
Journal, 
26(1), 
77-84. 
doi:10.1177/009286159202600108 
bKarvanen, J., Signal Processing Laboratory, Helsinki University of Technology, Helsinki, 
Finland. (2003). The Statistical Basis of Laboratory Data Normalization. Drug Information 
Journal, 37(1), 101-107. doi:10.1177/009286150303700112 
cInternational Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH). (1996). Guideline for Industry, Structure and Content of Clinical Study 
Reports (ICH E3). 
 
 
 
 
 
 
 
 
 
 
 
  
 
End of document 
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