Conditions: Respiratory Syncytial Virus Infection
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: yes

Brief summary:
The purpose of the study is to learn about:

* The activity of sisunotavir in the body over a period. It includes the processes by which sisunotavir is absorbed, distributed in the body, localized in the tissues, and removed from the body.
* safety and tolerability of sisunatovir (PF-07923568) in Chinese healthy adult participants.

This information is being collected to support further clinical development as well as medicine registration in China.

This study is seeking for participants who:

* are male and female participants aged 18 to 65 years of age.
* are male and female participants who are healthy as seen by medical tests.
* have body mass index (BMI) of 19 to 27 kg/m2 and a total body weight of more than 50 kilograms (110 pounds).

About 12 participants will receive sisunatovir. Four capsules (strength=50 milligrams, 200 milligrams in total) of Sisunatovir will be given on Day 1 on empty stomach. This will be followed by 8 capsules of sisunatovir with 12 hours gap in between four capsules from Days 4 to 7. The participants will have to take 4 capsules of sisunatovir in the morning of 8th day with a meal.

The total time of participants will be in the study is about 71 days. This includes the screening visit to the Follow-up contact. In screening visit, participants will be tested to see if they are fit to take part in the study.

Detailed description:

Arms:
arm 1: This only arm will be given as a single dose on Day 1 in a fasted state followed by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state

Interventions: intervention 1: Sisunatovir
Intervention descriptions: intervention 1: Will be given as a single dose on Day 1 in a fasted state followed by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state

Protocol document:
Prot_000.pdf: 
PF-07923568
Protocol C5241018
Final Protocol, 09 June 2023
PFIZER CONFIDENTIAL
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Page 1
Title Page
A PHASE 1, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE 
PHARMACOKINETICS, SAFETY, AND TOLERABILITY FOLLOWING SINGLE AND 
MULTIPLE DOSES OF SISUNATOVIR IN CHINESE HEALTHY PARTICIPANTS
Study Intervention Number:
PF-07923568
Study Intervention Name:
Sisunatovir
US IND Number:
NA
EudraCT/EU CT Number:
NA
ClinicalTrials.gov ID:  
NA
Pediatric Investigational Plan Number:
NA
Protocol Number:
C5241018
Phase:
1
Sponsor Legal Address:
Pfizer Inc.
66 Hudson Boulevard East
New York, NY 10001
Brief Title: A Study to Learn How the Study Medicine Called Sisunatovir is Tolerated 
and Acts in the Body in Chinese Healthy Adults
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Document History
Document
Version Date
Original protocol
09 June 2023
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ....................................................................................................................12
1.3. Schedule of Activities .............................................................................................13
2. INTRODUCTION ...............................................................................................................18
2.1. Study Rationale .......................................................................................................18
2.2. Background .............................................................................................................18
2.2.1. Nonclinical Pharmacology..........................................................................19
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................19
2.2.3. Nonclinical Safety ......................................................................................20
2.2.4. Clinical Overview.......................................................................................20
2.3. Benefit/Risk Assessment.........................................................................................24
2.3.1. Risk Assessment.........................................................................................24
2.3.2. Benefit Assessment.....................................................................................25
2.3.3. Overall Benefit/Risk Conclusion................................................................25
3. OBJECTIVES AND ENDPOINTS.....................................................................................26
4. STUDY DESIGN.................................................................................................................26
4.1. Overall Design.........................................................................................................26
4.2. Scientific Rationale for Study Design.....................................................................27
4.2.1. Choice of Contraception/Barrier Requirements .........................................27
4.3. Justification for Dose ..............................................................................................28
4.4. End of Study Definition ..........................................................................................28
5. STUDY POPULATION......................................................................................................28
5.1. Inclusion Criteria.....................................................................................................29
5.2. Exclusion Criteria....................................................................................................29
5.3. Lifestyle Considerations..........................................................................................32
5.3.1. Contraception..............................................................................................32
5.3.2. Meals and Dietary Restrictions...................................................................32
5.3.3. Caffeine, Alcohol, and Tobacco .................................................................33
5.3.4. Activity .......................................................................................................33
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5.4. Screen Failures ........................................................................................................34
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................34
6.1. Study Intervention(s) Administered........................................................................34
6.1.1. Administration............................................................................................35
6.2. Preparation, Handling, Storage, and Accountability...............................................36
6.2.1. Preparation and Dispensing........................................................................37
6.3. Assignment to Study Intervention...........................................................................37
6.4. Blinding...................................................................................................................37
6.5. Study Intervention Compliance...............................................................................37
6.6. Dose Modification...................................................................................................38
6.7. Continued Access to Study Intervention After the End of the Study......................38
6.8. Treatment of Overdose............................................................................................38
6.9. Prior and Concomitant Therapy..............................................................................38
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................39
7.1. Discontinuation of Study Intervention ....................................................................39
7.1.1. Potential Cases of Acute Kidney Injury .....................................................39
7.1.2. Liver Injury.................................................................................................41
7.1.3. ECG Changes..............................................................................................41
7.1.4. COVID-19 ..................................................................................................41
7.2. Participant Discontinuation/Withdrawal From the Study.......................................41
7.2.1. Withdrawal of Consent...............................................................................42
7.3. Lost to Follow-Up ...................................................................................................42
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................43
8.1. Administrative and Baseline Procedures.................................................................43
8.1.1. Baseline Procedures....................................................................................44
8.2. Efficacy Assessments..............................................................................................44
8.3. Safety Assessments .................................................................................................44
8.3.1. Physical Examinations................................................................................44
8.3.2. Chest Radiography......................................................................................45
8.3.3. Vital Signs ..................................................................................................45
8.3.3.1. Blood Pressure and Pulse Rate..................................................45
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8.3.3.2. Temperature ..............................................................................46
8.3.4. Electrocardiograms.....................................................................................46
8.3.5. Clinical Safety Laboratory Assessments ....................................................46
8.3.6. COVID-19 Specific Assessments...............................................................47
8.3.7. Pregnancy Testing ......................................................................................47
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................48
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......48
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................49
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................49
8.4.2. Method of Detecting AEs and SAEs ..........................................................50
8.4.3. Follow-Up of AEs and SAEs......................................................................50
8.4.4. Regulatory Reporting Requirements for SAEs...........................................50
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................51
8.4.5.1. Exposure During Pregnancy......................................................51
8.4.5.2. Exposure During Breastfeeding ................................................52
8.4.5.3. Occupational Exposure .............................................................53
8.4.6. Cardiovascular and Death Events...............................................................53
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................53
8.4.8. Adverse Events of Special Interest.............................................................53
8.4.8.1. Lack of Efficacy........................................................................53
8.4.9. Medical Device Deficiencies......................................................................53
8.4.10. Medication Errors.....................................................................................53
8.5. Pharmacokinetics ....................................................................................................54
8.6. Genetics...................................................................................................................55
8.6.1. Specified Genetics ......................................................................................55
8.6.2. Retained Research Samples for Genetics ...................................................56
8.7. Biomarkers ..............................................................................................................56
8.8. Immunogenicity Assessments.................................................................................56
8.9. Health Economics ...................................................................................................56
9. STATISTICAL CONSIDERATIONS ................................................................................56
9.1. Statistical Hypotheses .............................................................................................56
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9.2. Analysis Sets ...........................................................................................................56
9.3. Statistical Analyses .................................................................................................57
9.3.1. Pharmacokinetic Analyses..........................................................................57
9.3.1.1. Statistical Methods for Pharmacokinetic Data..........................57
9.3.1.2. Derivation of Pharmacokinetic Parameters Prior to 
Analysis .............................................................................................57
..............................................................58
9.3.2. Safety Analyses ..........................................................................................59
9.3.2.1. Electrocardiogram Analyses......................................................59
9.4. Interim Analyses .....................................................................................................59
9.5. Sample Size Determination.....................................................................................59
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................60
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............60
10.1.1. Regulatory and Ethical Considerations ....................................................60
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................60
10.1.2. Financial Disclosure .................................................................................61
10.1.3. Informed Consent Process ........................................................................61
10.1.4. Data Protection .........................................................................................62
10.1.5. Committees Structure ...............................................................................62
10.1.5.1. Data Monitoring Committee ...................................................62
10.1.6. Dissemination of Clinical Study Data ......................................................62
10.1.7. Data Quality Assurance ............................................................................63
10.1.8. Source Documents....................................................................................65
10.1.9. Use of Medical Records............................................................................65
10.1.10. Study and Site Start and Closure ............................................................66
10.1.11. Publication Policy...................................................................................66
10.1.12. Sponsor’s Medically Qualified Individual..............................................67
10.2. Appendix 2: Clinical Laboratory Tests .................................................................68
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................69
10.3.1. Definition of AE .......................................................................................69
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10.3.2. Definition of an SAE ................................................................................70
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................71
10.3.4. Reporting of SAEs....................................................................................75
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................76
10.4.1. Male Participant Reproductive Inclusion Criteria....................................76
10.4.2. Female Participant Reproductive Inclusion Criteria.................................76
10.4.3. Woman of Childbearing Potential ............................................................77
10.4.4. Contraception Methods.............................................................................78
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments .......80
10.6. Appendix 6: Kidney Safety: Monitoring Guidelines ............................................82
10.6.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury..............................................................................82
10.6.2. Age-Specific Kidney Function Calculation Recommendations...............82
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations ...........................................................................................82
10.6.3. Kidney Function Calculation Tools..........................................................82
10.6.4. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities...................................................................................................83
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................84
10.8. Appendix 8: Prohibited Concomitant Medications That May Result in DDI.......86
10.9. Appendix 9: Abbreviations ...................................................................................88
11. REFERENCES ..................................................................................................................92
LIST OF TABLES
Table 1.
Study Schedule of Assessment.................................................................13
Table 2.
Pharmacokinetic Sampling Times ............................................................17
Table 3.
Completed Sisunatovir Studies.................................................................21
Table 4.
Plasma PK Parameters for Sisunatovir.....................................................57
Table 5.
Protocol-Required Laboratory Assessments.............................................68
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: 
A Phase 1, Open-Label, Single-Arm Study to Evaluate the Pharmacokinetics, Safety, and 
Tolerability Following Single and Multiple Doses of Sisunatovir in Chinese Healthy 
Participants
Brief Title: A Study to Learn How the Study Medicine Called Sisunatovir is Tolerated and 
Acts in The Body in Chinese Healthy Adults
Regulatory Agency Identification Number(s):
US IND Number:
Not applicable
EudraCT/EU CT Number:
Not Applicable
ClinicalTrials.gov ID:  
Not Available
Pediatric Investigational Plan Number:
Not Applicable
Protocol Number:
C5241018
Phase:
1
Rationale:
The purpose of the study is to evaluate the PK, safety and tolerability of sisunatovir 
(PF-07923568) in Chinese healthy adult participants. This information is being collected to 
support further clinical development as well as drug registration in China.
Objectives and Endpoints:
Objectives
Endpoints
Primary: 
Primary:

To evaluate the PK of sisunatovir after single 
dose and multiple doses in Chinese healthy 
participants
Sisunatovir plasma exposure for single and multiple doses: 
Post dose on Day 1: Cmax, AUClast, AUCtau (tau=12), and
AUCinf as data permit.
Post first dose on Day 4: Cmax, AUCtau
Post dose on Day 8: Cmax, AUCtau
Secondary: 
Secondary:

To further characterize the PK profile of 
sisunatovir after single dose and multiple doses 
in Chinese healthy participants
Additional sisunatovir plasma PK parameters: 
Post dose on Day 1: Tmax, t½, MRT, Vz/F, and CL/F as data 
permit
Post first dose on Day 4: Tmax
Post dose on Day 8: Tmax, t½ , accumulation ratio on AUCtau
(Rac) and on Cmax (Rac,Cmax), MRT, Vz/F, CL/F, Ctrough, Cav, 
AUClast, AUCinf and PTR as data permit
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Objectives
Endpoints

To evaluate the safety and tolerability of 
sisunatovir following single and multiple doses
in Chinese healthy participants

AEs/SAEs, clinical safety laboratory tests, vital signs, 12-lead 
ECGs
Overall Design:
This is a Phase 1, single-center, open-label and single arm study to investigate PK, safety and 
tolerability of sisunatovir of 200 mg administered as a single dose on Day 1 in a fasted state 
followed by repeated twice daily doses (Q12 hours) from Days 4-7 plus 1 morning dose on 
Day 8 in a fed state in Chinese healthy participants. 
Approximately 12 participants will receive sisunatovir. 
Number of Participants:
Approximately 12 participants will be enrolled in the study. Participants who fail to complete 
the study may be replaced at the discretion of the sponsor and investigator. 
Note: “Enrolled” means participants’, or their legally authorized representative’s, agreement 
to participate in a clinical study following completion of the informed consent process and 
assignment to study intervention.
Study Population:
Key inclusion and exclusion criteria are listed below:
Inclusion Criteria 
Participants must meet the following key inclusion criteria to be eligible for enrollment into 
the study:
1. Chinese male and female participants aged 18 to 65 years of age, inclusive, at the 
time of signing of the informed consent document (ICD).
2. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, physical examination, standard 12-lead ECG, 
and laboratory tests.
3. Body mass index (BMI) of 19 to 27 kg/m2; and a total body weight >50 kg (110 lb). 
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Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).

Any condition possibly affecting drug absorption (eg, gastrectomy, 
cholecystectomy).
2. Any medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality, or other conditions or situations 
related to coronavirus disease 2019 (COVID-19) pandemic that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
3. Use of prescription or nonprescription drugs and dietary and herbal supplements
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention with the exception of moderate/strong cytochrome P4503A (CYP3A)
inducers or time-dependent inhibitors which are prohibited within 14 days plus 5 
half-lives prior to the first dose of study intervention.
4. A positive urine drug test, confirmed by a repeat test, if deemed necessary.
5. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) 
or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of 
the 3 BP values should be used to determine the participant’s eligibility.
6. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTc corrected using 
Fridericia’s formula [QTcF] >450 ms, complete left bundle branch block [LBBB], 
signs of an acute or indeterminate- age myocardial infarction, ST-segment and 
T-wave [ST-T] interval changes suggestive of myocardial ischemia, second- or third-
degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the 
uncorrected QT interval is >450 ms, this interval should be rate-corrected using the 
Fridericia method only and the resulting QTcF should be used for decision making 
and reporting. If QTcF exceeds 450 ms, or quantitative restrictions (QRS) exceeds 
120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS 
values used to determine the participant’s eligibility. Computer interpreted- ECGs 
should be overread by a physician experienced in reading ECGs before excluding a 
participant.
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7. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary:

Glomerular filtration rate (GFR) <60 mL/min/1.73m2 based on chronic kidney 
disease epidemiology (CKD-EPI equation);

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 
≥1.05 × upper limit of normal (ULN); 

Gamma-glutamyl transferase (GGT) > 1.05 × ULN; 

Alkaline phosphatase > 1.05 × ULN; 

Total bilirubin level ≥1.05 × ULN; participants with a history of Gilbert’s 
syndrome may have direct bilirubin measured and would be eligible for this 
study provided the direct bilirubin level is ≤ULN.
Study Arms and Duration:
The duration of the study for a participant will be up to approximately 71 days and includes:

Screening period: up to ~28 days (Day -28 to Day -1)

Clinical confinement period (Treatment period): 12 days (Day -1 to Day 11)

Outpatient follow-up period: ~26 to 33 days (Day 11 to Day 37-44)
A follow up contact will be completed at least 28 calendar days and up to 35 calendar days 
after the last dose of sisunatovir to capture any potential AEs and concomitant treatments, 
and to confirm appropriate contraception usage. This follow-up assessment may be 
conducted via telephone.
Study Intervention(s)
Intervention Name
PF-07923568 (sisunatovir)
Use
Experimental
IMP or NIMP/AxMP
IMP
Dose Formulation
Capsule
Unit Dose Strength(s)
50 mg
Route of Administration
Oral
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Study Arm(s)
Arm Title
Sisunatovir 200 mg
Arm Description
Participants will receive sisunatovir of 200 mg administered as a single 
dose on Day 1 in a fasted state followed by repeated twice daily doses 
(Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state.
Statistical Methods:
There is no statistical hypothesis for this study, therefore, the study sample size is not based 
on any statistical decision rule. The sample size of approximately 12 Chinese participants is 
based on the China regulatory requirement for a China PK study and to support the 
registration in China. Based on previous experience, the chosen sample size of 
12 participants is considered to be sufficient to fulfill the objectives of the study and the need 
to minimize exposure to healthy participants. Participants who fail to complete the study may 
be replaced at the discretion of the sponsor and investigator. 

The plasma PK parameters for sisunatovir, following single dose in a fasted state and 
repeated twice daily doses in a fed state, will be derived from the plasma 
concentration-time profiles. Actual PK sampling times will be used in the derivation of 
PK parameters. Sisunatovir PK parameters will be listed and descriptively summarized 
by study day. Box and whisker plots will be generated for AUClast, AUCinf, AUCtau, and 
Cmax. The plasma concentrations of sisunatovir will be listed and descriptively 
summarized by study day and nominal PK sampling times. Individual participant and 
summary profiles (mean and median plots) of the plasma concentration-time data will be 
plotted using actual and nominal sampling times, respectively.

Safety data (AEs, ECGs, vital signs, and safety laboratory data) will be summarized and
presented in tabular format where appropriate.
Ethical Considerations:
Sisunatovir is not expected to provide any clinical benefit to healthy participants. This study 
is designed primarily to generate safety, tolerability and pharmacokinetic data in healthy 
Chinese participants for further clinical development.
1.2. Schema
Not applicable.
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Table 1.
Study Schedule of Assessment
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 9.
Screen
Single Dose Period
Multiple Dose Period
F/U
ET
Notes
Days Relative to Day 1
Day -
28 to 
Day -2
Day 
-1
Day 
1
Day 
2
Day
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day
9
Day
10
Day
11
28-35 
days 
after 
last 
dosing

All screening should be done ≤28 
days before the first dose. 

Day relative to start of study 
intervention (Day 1).

Follow-up may occur via telephone 
contact and must occur 28 to 35 days 
after administration of the last dose of 
study intervention. 
Informed consent
X

Informed consent should be obtained 
prior to undergoing any study-
specific procedures. 

See Section 10.1.3 for additional 
information.
CRU confinement
X










X
Inclusion/exclusion criteria
X
X
Medical/medication history
X
X
Physical exam
X
X
X

PE at Screening or Day -1 only. A 
brief PE at other times at the 
discretion of the investigator. 

Including height and weight at 
screening only.
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Table 1.
Study Schedule of Assessment
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 9.
Screen
Single Dose Period
Multiple Dose Period
F/U
ET
Notes
Days Relative to Day 1
Day -
28 to 
Day -2
Day 
-1
Day 
1
Day 
2
Day
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day
9
Day
10
Day
11
28-35 
days 
after 
last 
dosing

All screening should be done ≤28 
days before the first dose. 

Day relative to start of study 
intervention (Day 1).

Follow-up may occur via telephone 
contact and must occur 28 to 35 days 
after administration of the last dose of 
study intervention. 
Safety laboratory
X
X
X
X
X
X

Participants should fast for at least 4 
hours before safety labs are drawn, 
see Table 5.

Include urinalysis.
Demography
X
Pregnancy test (WOCBP 
only)
X
X
X

ET pregnancy testing only if 
participant withdraws while not 
admitted to the CRU.
Contraception check 
X
X
X
X
X
FSH (post-menopausal 
women only)
X
Alcohol breath test
X
Urine drug testing
X
X
Single 12-Lead ECG
X
X
X
X

On Day 1, at pre-dose (-1 hour) and 6 
hours (±15 minutes) post-dose. 
Vital signs
X
X
X
X

Vital signs include supine blood 
pressure, pulse rate, and temperature.

On Day 1, at pre-dose (-1 hour) and 
6 hours (±15 minutes) post-dose.
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Table 1.
Study Schedule of Assessment
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 9.
Screen
Single Dose Period
Multiple Dose Period
F/U
ET
Notes
Days Relative to Day 1
Day -
28 to 
Day -2
Day 
-1
Day 
1
Day 
2
Day
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day
9
Day
10
Day
11
28-35 
days 
after 
last 
dosing

All screening should be done ≤28 
days before the first dose. 

Day relative to start of study 
intervention (Day 1).

Follow-up may occur via telephone 
contact and must occur 28 to 35 days 
after administration of the last dose of 
study intervention. 
Chest radiography
X

Chest X-ray or other appropriate 
diagnostic imaging (ie, CT or MRI) 
should be performed at screening 
(unless taken within 3 months prior 
to the screening). 

Chest X-rays are required and should 
be performed as per local guidelines. 
See Section 8.3.4.
Serology: HIV, HBsAg, 
HBsAb, HBcAb, HCVAb
and serological reaction of 
syphilis
X
HBVDNA
X

May be not needed. Refer to 
Section 5.2
COVID-19 related 
procedures
X
X











X
X

Performed per local procedures
Study intervention 
administration
X
X
X
X
X
X

BID on Days 4-7 and QD in AM on 
Day 8
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Table 1.
Study Schedule of Assessment
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 9.
Screen
Single Dose Period
Multiple Dose Period
F/U
ET
Notes
Days Relative to Day 1
Day -
28 to 
Day -2
Day 
-1
Day 
1
Day 
2
Day
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day
9
Day
10
Day
11
28-35 
days 
after 
last 
dosing

All screening should be done ≤28 
days before the first dose. 

Day relative to start of study 
intervention (Day 1).

Follow-up may occur via telephone 
contact and must occur 28 to 35 days 
after administration of the last dose of 
study intervention. 
Pharmacokinetic blood 
sampling
X
X
X
X
X
X
X
X
X
X
X

PK sampling (Table 2) at 0 hour prior 
to morning dose on Day 6 and Day 7

On Day 1 and Day 4, PK sampling at 
0 hour (-15 minutes) prior to 
morning dose; time window for 
other PK sampling refer to 
Section 8.5.
CRU discharge 
X
Serious and nonserious AE 
monitoring
X














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Table 2.
Pharmacokinetic Sampling Times
Visit Identifier 
On-Treatment Period
Notes
Study Day
Day 1, Day 4 and Day 8
Hours Before/After Dose
0
1
2
3
4
5
6
8
10
12
14
24
48
72
Hour 0 = predose sample 
collection
Study intervention 
administration
X
X

Dosing at 12 hours only 
on Day 4
PK blood sampling on Day 1 
and Day 8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling on Day 4
X*
X
X
X
X
X
X
X
X
X

PK sample at 0 hour on 
Day 4 is the same 
sample at 72 hours post 
dose on Day 1.

PK sample at 12 hours 
post-dose must be 
collected prior to 
dosing;
PK microsampling (Tasso®)
(if feasible)
X
X
X
X
X

Time-matched to PK 
blood sampling. To be 
collected on Day 4 only.
Blood/Plasma ratio sampling
(if feasible)
X
X
X

Whole blood to be 
aliquoted from PK 
blood samples on Day 4
only.
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2. INTRODUCTION
PF-07923568 (sisunatovir, formerly RV521) is being developed to act as a highly potent, 
selective, orally available agent to treat RSV infection. Sisunatovir is an inhibitor of RSV 
fusion (F) protein mediated fusion that is currently being investigated for the treatment of 
RSV infection.
2.1. Study Rationale 
The purpose of the study is to evaluate the PK, safety and tolerability of sisunatovir 
(PF-07923568) in Chinese healthy adult participants. This information is being collected to 
support further clinical development as well as drug registration in China.
2.2. Background 
RSV, a member of the Pneumovirus family, is a significant pathogen of the very young, 
immunocompromised, and the elderly. RSV is ubiquitous and is known to infect almost all 
children by 2 years of age.1
The clinical manifestation of RSV infection is typically mild upper respiratory tract illness. 
However, in infants, young children, the immunocompromised and the elderly, it can cause 
serious LRTI. Infants <6 months of age are at the highest risk of severe RSV infection which 
can lead to hospitalization, ICU admission and even death.2,3,4
The current management of RSV infection includes a combination of preventative and 
limited treatment measures, primarily consisting of supportive care. There are, as yet, no 
RSV vaccines approved in China and only 1 approved antivirals available. Ribavirin, is a 
nucleoside analogue, but clinical use is restricted due to its limited antiviral potency, delivery 
route, toxicity and teratogenic potential.5,6 Most current guidelines make either no 
recommendation or do not recommend routine use of ribavirin.7 The monoclonal antibody 
Synagis® (palivizumab) which interacts with F glycoprotein of the RSV virus and has been 
approved in the US and EU.8,9 Palivizumab (Synagis®) has been shown to provide protection 
in infants at risk of severe disease, but needs to be given before infection and is administered 
monthly throughout the winter season.9 It is approved for use in infants with a history of 
prematurity, hemodynamically significant cardiac disease or chronic lung disease of 
prematurity. Recently (November 2022), Nirsevimab, a monoclonal antibody to the RSV 
fusion (F) protein that has an extended half-life, was approved for prevention of RSV-LRTI 
in newborns and infants during their first RSV season in the EU.10 Despite the availability of 
these agents, their limited use means that treatment of RSV infection remains an area of 
unmet need. 
Sisunatovir (PF-07923568) is a potent inhibitor of RSV F protein mediated cell-to-cell fusion 
and exerts antiviral activity against RSV by inhibiting viral entry into host cells. In this way, 
F protein inhibition may reduce both viral replication and pathology, reducing the severity of 
RSV-LRTI. Thus, sisunatovir may provide clinical benefit to pediatric participants with RSV 
disease. 
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Sisunatovir is a new oral, non-biologic treatment that targets the RSV F protein. Approved 
prophylactic treatments (Palivizumab and Nirvesimab in EU)10,9 also target the RSV F 
protein. 
The sisunatovir preclinical profile, as well as the safety and tolerability data from the first 
human dosing studies, provide a strong rationale for the clinical development of sisunatovir.
2.2.1. Nonclinical Pharmacology
In vitro, sisunatovir has demonstrated potent inhibition of RSV F-protein-mediated 
cell-to-cell fusion, and of infection by a panel of RSV laboratory and clinical isolates of both 
A and B strains in the RSV plaque assay. Sisunatovir treatment resulted in a significant 
reduction in RSV infection in a human airway epithelial cell model.
In vivo, sisunatovir resulted in a marked reduction in lung virus titer in a BALB/C mouse 
model of RSV infection.
An in vitro secondary pharmacology study did not reveal any significant off-target-activity 
for sisunatovir.
Refer to the sisunatovir IB for further details.
2.2.2. Nonclinical Pharmacokinetics and Metabolism
In animal pharmacokinetic studies sisunatovir showed slow oral absorption, moderate-high 
CL, high volume of distribution, and oral bioavailability of 46%, 42-132%, and 44% in 
mouse, rat, and dog, respectively. 
Plasma protein binding of sisunatovir was low to moderate across species, with average 
fraction unbound of 67%, 38%, 52%, 27%, and 48% in human, mouse, rat, dog and guinea 
pig, respectively. Repeat dosing studies in the rat show that extensive distribution of 
sisunatovir to the lungs occurs, resulting in high lung to plasma ratio. This effect is greater 
than dose proportional from 50 mg/kg to 150 mg/kg.
Consistent with the results of the midazolam DDI study (C5421004), in vitro studies indicate 
that CYP3A4 is the main CYP isoform that metabolizes sisunatovir with minor contribution 
from CYP 2D6.
In vitro studies indicate a DDI risk exists for OATP1B1/1B3, OCT1, MATE1, OCT2, and 
OAT3. However, ratios of unbound hepatic inlet concentrations relative to Ki values are low, 
and DDI risk is considered unlikely for OATPs, OCT2, and OAT3. The pharmacokinetics of 
OCT1 and MATE1 substrates may be altered when co-administered with sisunatovir, and 
therefore sensitive OCT1 and MATE1 substrates are prohibited in this protocol 
(Appendix 8).
In vitro studies indicate there is a risk of inhibition of CYPs 1A2, 2B6, 2C9, 2C19, and 3A4. 
The DDI with CYPs 1A2, 2B6, 2C9, and 2C19 is predicted to be minimal (predicted less 
than 25% increase in AUC of a sensitive substrate). 
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In vitro studies indicate that sisunatovir is a P-gp substrate; therefore, co-administration of 
inhibitors for the transporter (P-gp) may result in increased exposure to sisunatovir 
(approximately 2-fold). 
Refer to the sisunatovir IB for further details.
2.2.3. Nonclinical Safety
In the repeat dose toxicity studies in adult (up to 28 days) and neonatal/juvenile rats and 
dogs, the MTDs were defined by body weight loss and reduced food consumption 
accompanied by adverse clinical observation of varying severity. In dogs, there was 
dose-related incidence of emesis and liquid feces at ≥15 mg/kg/day. The key target organ for 
toxicity in adult animals was the hepatobiliary system, which included both degenerative and 
inflammatory changes in bile duct, in rats (≥60 mg/kg/day) and dogs (≥45 mg/kg/day). In 
dogs, the hepatobiliary findings correlated with elevated plasma levels of ALP, ALT and 
GGT. In addition, the findings observed only in rats were in kidney 
(degeneration/regeneration of medullary tubules) at ≥120 mg/kg/day, heart 
(degeneration/necrosis of the myocardium) and lung (vascular degeneration/necrosis) at 
240 mg/kg/day (non-tolerated dose) and trachea (epithelial degeneration and/or subepithelial 
inflammation [predominantly in females]) at 120 mg/kg/day in 14 and/or 28-day studies. In 
the 28-day dog repeat dose toxicity study, the NOAEL was 15 mg/kg/day corresponding to 
Cmax of 729 ng/mL and AUCtau of 9510 ng.h/mL. In the 28-day rat repeat dose toxicity study, 
the NOAEL was 60 mg/kg/day corresponding to Cmax of 322 ng/mL and AUCtau of 
4725 ng.h/mL.
In the embryo-fetal toxicity studies in rat (GD6-17) and rabbit (GD6-18), there were no 
effects on pregnancy or embryo-fetal development. In rat, the NOAEL for maternal toxicity 
was 45 mg/kg/day based on the transient initial body weight loss followed by dose-related 
decreased body weight gain at ≥45 mg/kg/day. The NOAEL for embryo-fetal toxicity in rat 
was 60 mg/kg/day, corresponding to systemic maternal exposure (AUC24) of 9830 ng•h/mL 
on Day 15 of gestation. In rabbit, maternal toxicity was limited to lower body weight gain 
and food intake at 45 mg/kg/day. The NOAEL for embryo-fetal development in rabbit was 
45 mg/kg/day, corresponding to a systemic maternal exposure (AUC24) of 220 ng•h/mL on 
Day 16 of gestation.
Further details of the nonclinical toxicology program are included in the IB.
2.2.4. Clinical Overview
To date, 5 clinical studies of sisunatovir have been completed; each study was conducted in 
healthy adults. Key design features of the completed clinical studies are provided in Table 3, 
and summaries of the key clinical pharmacology, clinical efficacy and clinical safety data 
from the completed studies are provided in the sections below.
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Table 3.
Completed Sisunatovir Studies
Study Number
(Status)
Study Type/Key 
Design Features
Study Population
Dose, Dosing 
Regimen
Formulation Used
C5241001
(previously 
REVC001)
(completed)
Phase 1, 
randomized, double-
blind, placebo-
controlled, SAD and 
MAD study to 
evaluate the safety, 
tolerability, PK, and 
food and 
formulation effect
Healthy participants
Part A (SAD): 
24 Caucasian and 
12 Japanese
Part A: 10, 30, 60, 
175, 250, 350, or 
525 mg single dose
DICa
Part B (MAD): 24
healthy participants
Part B: 175, 250, or 
350 mg BID x 5 
days for a total of 9 
doses
DICa
Part C (food effect 
and formulation): 16
healthy participants
Part C: 200 mg 
single dose
DICa
Liquid Formulationa
C5241002-
previously REVC002 
(completed)
Phase 2a, 
randomized, 
double-blind, 
placebo-controlled
Healthy participants 
inoculated with 
RSV Challenge 
Virus (CV)
66 participants
200 mg or 350 mg 
BID for a total 
10 doses;
DIC
C5241003
Previously 
REVC003
(completed)
Phase 2, 
randomized, double-
blind, placebo-
controlled study to 
investigate PK, 
safety, and 
tolerability 
Hospitalized 
pediatric patients 
with RSV lower 
respiratory tract 
infection (LRTI):
Part A – 19
Part B – 32
Part A: single dose 
(2.5 mg/kg for 
participants 6-36
months, inclusive;
and 2 mg/kg for 
participants ≥1 
month to <6 months 
of age)
Part B: multiple 
doses (2.5 mg/kg in 
1-<6 months and up 
to 5 mg/kg in 6-36 
months) q12h for 5 
days
DPB
C5241004-
previously REVC004 
(completed)
Phase 1, adaptive, 
part-randomized, 
part open-label
study to 
evaluatedrug 
interactions, safety 
and tolerability
Healthy participants;
82
200 mg; BID;
DIC
C5241005-
previously REVC005 
(completed)
Phase 1, open-label, 
single-dose, study to 
evaluate the PK, 
safety, and 
tolerability
Healthy participants;
9
200 mg, 4 single 
doses total; 
1 ×: DIC (fed)
1 ×: DPB dispersed 
in H2O (fed)
1 ×: DPB dispersed 
in H2O (fasted) 
[wash-out: 3 days 
between each of the 
3 dosing days]
DIC
DPB
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Table 3.
Completed Sisunatovir Studies
Study Number
(Status)
Study Type/Key 
Design Features
Study Population
Dose, Dosing 
Regimen
Formulation Used
a.
A total of 8 participants received the liquid dosage formulation of sisunatovir in a solution, at a 
concentration of 5 mg/mL, containing hydroxypropyl-β-cyclodextrin (HBP cyclodextrin), Lycasin, 
flavoring agent (strawberry) benzoic acid and water, and 68 participants received DIC in the study.
There are 2 ongoing studies (recruitment completed for the first 2 studies):

A Phase 1 ADME study at a single US site (C5241008, previously denoted 
REVC008) to assess the metabolic fate of a radio-labeled oral dose of sisunatovir in 
healthy participants (recruitment completed in July 2022 with a clinical study report 
in preparation).

A Phase 1 PK study at a single Belgium PCRU site (C5241006) to assess the safety 
and tolerability, pharmacokinetics, and food effect of multiple oral doses of 
sisunatovir (PIC formulation). Additionally, the study is also designed to generate 
preliminary palatability data that will inform further development of formulations 
appropriate for future pediatric studies. 
A total of 201 adult healthy participants have received sisunatovir in 4 completed clinical 
studies (C5241001, C5241002, C5241004, and C5241005) investigating the PK profile, 
effects of food on PK, effects of formulation on PK (C5241001, C5241005), DDIs 
(C5241004), and the efficacy in an RSV Viral Challenge Study (C5241002) at doses ranging 
from 10 mg to 525 mg. In addition, in one completed pediatric study, 41 pediatric patients 
hospitalized due to RSV LRTI have received either a single dose (N = 19) or multiple BID 
doses of up to 5 days of sisunatovir in the ongoing C5241003 study (N=22).
In adult studies, the administration of sisunatovir was well tolerated at all doses, dosage 
forms, and dosing regimens tested. In the adult healthy participants treated to date, the 
occurrence of TEAEs considered related to sisunatovir has been low. Most commonly 
reported treatment-related TEAEs were in the GI disorders SOC; nausea, diarrhea, and 
abdominal pain. These TEAEs have been mild to moderate in intensity and resolved without 
sequelae.
As of 04 April 2023, there have been no SAEs attributable to sisunatovir and no deaths in the 
clinical studies. There has been one serious AE of pyrexia reported in the pediatric study 
(C5241003) in a child hospitalized with RSV infection who received a single dose of 
sisunatovir. This was considered serious because it prolonged hospitalization, but the SAE 
was reported as not related to IMP. In Study C5241002 there was 1 SAE of sub-acute
myocarditis reported for a participant on placebo; this was considered to be causally related 
to the challenge virus.
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In adults, sisunatovir is slowly absorbed reaching maximum plasma concentrations (Tmax) at 
5-6 hrs with a half-life of 7-10 hrs in healthy participants. Steady-state concentrations were 
reached after approximately 2 days of dosing and resulting in a 2-4 fold accumulation of 
exposure. AUC and Cmax values increased in a greater than dose proportional manner across 
single and multiple dose studies. Following 5 days of dosing, the variability in PK parameters 
was high, with %CV ranging from 67.4%-84% for Cmax and 71.9%-144% for AUC12.
The effect of food on the single dose PK was assessed for the DIC formulation and DPB 
formulation dispersed in water. For the DIC the extent of systemic exposure to sisunatovir 
(geometric mean AUCinf under fed and fasted conditions) was 357 and 221 ng•h/mL, 
respectively, with the between-subject variability being lower under fed conditions (%CV 
64.1% compared with 198%). The ratio of fed/fasted was 218% (90% CI 94.2% - 502%) for 
Cmax and 190% (90% CI 86.2% – 418%) for AUCinf. It should be noted that the DIC fasted 
results from C5241001 were lower than typically seen in other studies with 200 mg 
administered under fasting conditions, resulting in an artificially higher ratio of fed/fasted in 
this study. For the DPB dispersed in water the extent of systemic exposure to sisunatovir 
(geometric mean AUCinf) under fed and fasted conditions was 371 and 337 ng•h/mL, 
respectively, with the between-subject variability being slightly lower under fasted 
conditions (%CV 49.0% compared with 61.6%). The ratio of fed/fasted was 107.7% (90% CI 
78.0% – 148.8%) for Cmax and 110.0% (90% CI 85.6% – 141.4%) for AUCinf. 
Study C5241004 demonstrated that the disposition of sisunatovir was affected by moderate to 
strong inhibitors and inducers of CYP3A4. Furthermore, sisunatovir was demonstrated to be 
a moderate inhibitor of CYP3A4, so dose adjustments for compounds that are sensitive 
substrates for CYP3A4 may need to be considered.
In an RSV challenge study (C5241002), sisunatovir treatment resulted in a statistically 
significant reduction in AUC of RSV viral load compared with placebo; 55.25% (p=0.007) 
and 63.05% (p=0.002) for the 200 mg and 350 mg sisunatovir dose groups, respectively 
(dosed every 12 hrs [Q12H] for 5 days). Results for the AUC of total symptom score were 
consistent with the viral load AUC. Geometric mean AUCs of total symptom score were 
195.56, 30.79, and 31.76 hrs × score for placebo, 200 mg sisunatovir and 350 mg sisunatovir, 
respectively. The reduction in AUCs of total symptom score compared with placebo was 
statistically significant for both sisunatovir treatment groups; p=0.009 (84.26%) and p=0.002 
(83.76%), (Wilcoxon Rank-Sum test) for the 200 mg and 350 mg sisunatovir dose groups, 
respectively.
No participant in Study C5241001 had a QTcF interval change from baseline > 30 ms. 
Furthermore, no significant QTc prolongation was detected in C-QT analyses performed in 
SAD participants (C5241001), MAD participants (C5241001) or DDI study participants 
(C5241004).
More detailed information about results of clinical studies for sisunatovir may be found in the 
IB.
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2.3. Benefit/Risk Assessment
Sisunatovir is not expected to provide any clinical benefit to healthy participants. This study 
is designed primarily to generate safety, tolerability, and PK data for further clinical 
development.
For healthy participants participating in this study, no clinical benefit is expected. The 
purpose of the study is to provide the basis for further clinical development of sisunatovir as 
a potential new, pharmacological agent for the treatment of RSV LRTI. 
As of 14 September 2022, no specific human risks have been identified; postulated risks 
based on nonclinical studies are summarized in Section 2.2.3. The clinical impact of these 
potential risks will be minimized through standard, intensive, inpatient monitoring of the 
participants following administration of multiple oral doses of the study intervention.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of sisunatovir may be found in the IB, which is the SRSD for this study. Refer 
to the Study Intervention(s) table in Section 6.1 for a complete description of SRSDs,.
2.3.1. Risk Assessment
Potential Risk 
of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention PF-07923568
Hepatobiliary 
system effects
Degenerative and inflammatory changes in the 
bile duct of both rats (≥60 mg/kg/day) and dogs 
(≥45 mg/kg/day) in studies of up to 28 days, 
with elevated plasma levels of ALP, ALT, and 
GGT in dogs only. Evidence of recovery for all 
findings following a 14-day treatment-free 
period.
To date, mild transient elevations of liver 
enzymes have been observed in a few 
participants within clinical studies.
Standard monitoring including 
laboratory (ie, transaminases, ALP, 
GGT) and AE monitoring.
Gastrointestinal 
effects
Transient dose-related incidence of emesis and 
liquid feces in dogs at doses ≥15 mg/kg/day in 
studies up to 28 days. Additionally, 
inflammation in the duodenum, gall bladder, 
and liver at 45 mg/kg/day noted in 28-day dog 
study.
In completed adult clinical studies sisunatovir 
has been associated with mild GI AEs.
As this is an investigational agent, there 
is some risk that is mitigated by close 
observation of AEs, etc. Participants 
will be closely evaluated in an inpatient 
setting to monitor for GI AEs. If 
needed, palliative alleviating measures 
such as antiemetics may be provided.
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Potential Risk 
of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Cardiovascular 
effects
Myocardial degeneration and necrosis were 
noted at 240 mg/kg/day (non-tolerated dose) in 
a 14-day rat study.
No similar effect in rats at 120 mg/kg/day in 
the 28-day study, or in dogs at any dose, for 
14 or 28 days.
To date, Phase 1 studies in healthy participants 
and a Phase 1b study in pediatric participants
has not shown clinically significant changes in 
safety laboratory parameters (including 
troponin in C5241001), ECGs and vital signs 
related to Sisunatovir.
Monitoring will include VS, including 
heart rate and ECG assessments.
Other
Risk of 
COVID-19 
exposure during 
study
During the pandemic, study participants could 
be exposed to the SARS-CoV-2 virus during 
study participation. This could lead to increased 
health risk for this participant and others in the 
study.
Assessment of risk for, symptoms of, 
or testing for COVID-19 may be 
performed at screening, admission to 
the CRU, and/or at other times during 
the study at investigator discretion and 
according to local site policies.
2.3.2. Benefit Assessment
For healthy participants participating in this study, no clinical benefit is expected.
2.3.3. Overall Benefit/Risk Conclusion
This study is designed primarily to generate PK, safety, and tolerability data in Chinese
individuals.
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with sisunatovir are justified by the broader potential benefits to 
patients with RSV, if further development of sisunatovir is successful.
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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary:

To evaluate the PK of sisunatovir after single 
dose and multiple doses in Chinese healthy 
participants
Sisunatovir plasma exposure for single and multiple doses: 

Post dose on Day 1: Cmax, AUClast, AUCtau (tau=12), and
AUCinf as data permit.

Post first dose on Day 4: Cmax, AUCtau

Post dose on Day 8: Cmax, AUCtau
Secondary: 
Secondary:

To further characterize the PK profile of 
sisunatovir after single dose and multiple doses 
of sisunatovir in Chinese healthy participants
Additional sisunatovir plasma PK parameters: 

Post dose on Day 1: Tmax, t½, MRT, Vz/F, and CL/F as data 
permit

Post first dose on Day 4: Tmax

Post dose on Day 8: Tmax, t½, accumulation ratio on AUCtau
(Rac) and on Cmax (Rac,Cmax), MRT, Vz/F, CL/F, Ctrough, Cav, 
AUClast, AUCinf and PTR as data permit

To evaluate the safety and tolerability of 
sisunatovir following single and multiple dose 
in Chinese healthy participants

AEs/SAEs, clinical safety laboratory tests, vital signs, 12-lead 
ECGs
Tertiary/Exploratory: 
Tertiary/Exploratory:

To explore PK of sisunatovir by microsampling
technique, if feasible

Concentration of sisunatovir from paired samples obtained 
via microsampling compared to plasma sampling (if possible)
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, single-center, open-label and single-arm study to investigate PK, safety and 
tolerability of 200 mg sisunatovir given as a single dose on Day 1 in a fasted state followed 
by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose 
on Day 8 in a fed state in Chinese healthy participants. Approximately 12 participants in total 
will be included in this study. If a participant discontinues before completing the study, or
withdraws for reasons unrelated to the safety of the treatment, the participant may be 
replaced at the discretion of the investigator upon consultation with the sponsor.
A summary of the schedule of study participation and procedures is provided (see Schedule 
of Activities). The study will consist of a Screening visit, a Treatment period of single dosing
(Day -1 to Day 3) and multiple dosing (Day 4 to Day 11), and a Follow-up contact. The total 
duration of participation from the Screening visit to the Follow-up contact will be up to 
approximately 71 days.
The study period will begin with informed consent from the first participant and will end 
with the follow up examination of the last participant.
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Informed consent to participate in the study will be obtained before initiation of any 
trial-related activities. Screening examination will be conducted within 28 days before the 
first study drug administration. Participants will be admitted to the CRU on Day -1, 1 day 
before the first study drug administration. On Day 1 after fasting for at least 10 hours, all 
participants will receive a single oral dose of sisunatovir 200 mg at approximately 8:00 am ±
2 hours in the morning. The participants will be maintained in a fasted state for 4 hours after 
dosing and undergo serial PK blood sampling for 72 hours post-dose. On Days 4 to 7, 
participants will receive oral dose of sisunatovir 200 mg twice daily (Q12 hours) in a fed 
state. On Day 8, the dosing of sisunatovir will be administered under fed condition at 
approximately 8:00 am ± 2 hours in the morning. Participants may be discharged on Day 11 
after all study procedures are completed.
A follow up contact will be completed at least 28 calendar days and up to 35 calendar days 
after the last dose of investigational product to capture any potential AEs and concomitant 
treatments, and to confirm appropriate contraception usage. This follow-up assessment may 
be conducted via telephone.
4.2. Scientific Rationale for Study Design
The primary purpose of this study is to characterize the PK of sisunatovir in healthy Chinese 
adult participants. The selected dose in this study was well tolerated in previous clinical 
studies and therefore placebo control to evaluate safety is not needed. Males and females are 
to be recruited in the study.
Single- and multiple-dose periods are included in this study to allow characterization of the 
PK of sisunatovir following single dose and multiple doses in healthy Chinese participants. 
Repeated dosing for 5 days is sufficient for sisunatovir to reach its steady state, based on 
previous PK data and will permit comparison to PK data in Japanese and Westerners from 
Study C5241001, C5241005 and C5241006 which collected steady-state data on Day 5.
Blood sampling up to 72 hours post-dose is adequate for the characterization of the 
elimination phase for sisunatovir considering its half-life of 7-10 hours. 
Sisunatovir single dose on Day 1 will be administered without food in order to directly 
compare PK among Chinese, Japanese and Westerners. While given as repeated twice daily 
doses (Q12 hours) from Days 4-7 plus 1 morning dose on Day 8, sisunatovir will be given 
with food (typical Chinese breakfast, not high-fat high calorie) to mimic future clinical 
practice. Data obtained from such a design could also be helpful to preliminarily evaluate 
typical Chinese breakfast effect on the PK of sisunatovir.
If feasible, exploratory micro-sampling PK samples for the measurement of sisunatovir 
concentrations will be collected, in order to evaluate micro-sampling approach using the 
Tasso® device.
4.2.1. Choice of Contraception/Barrier Requirements 
Human reproductive safety data are limited for sisunatovir, but there is no suspicion of 
human teratogenicity based on the intended pharmacology of the compound. Therefore, the 
use of a highly effective method of contraception is required (see Appendix 4).
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4.3. Justification for Dose
The study dose and duration were selected based on the safety, tolerability and PK results in 
previous studies and the proposed clinical dose for future studies. The dose level of 200 mg 
BID is current proposed dose level for the following clinical development in adults. This 
dose was also studied in healthy participant studies C5241001, C5241005 and C5241006, 
which would allow the comparison of safety and PK among Westerner, Japanese and 
Chinese.
The single dose up to 525 mg for sisunatovir and multiple doses up to 350 mg BID × 5 days 
for a total dose of 9 doses were studied in Phase 1 study (C5241001), while a higher dose of 
400 mg BID × 5 days was studied in C5241006. Up to a single dose of 525 mg or multiple 
doses of 400 mg BID, sisunatovir was generally safe and well-tolerated in all healthy 
participants.  
The effect of food on the PK of sisunatovir has been variable in Phase 1 studies. However, 
the effect of food on the PK of sisunatovir using the formulation to be used in this study (dry 
powder blend in capsules) showed minimal food effect. Therefore, the concern of 
unacceptable safety and tolerability due to potentially higher exposure caused by food effect 
is not expected in Chinese healthy participants with administration of repeated twice daily 
doses (Q12 hours) of sisunatovir.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
A participant is considered to have completed the study if they have completed all visits of 
the study, including the last scheduled procedure shown in the SoA. Follow-up visits in 
addition to those in the SoA may be scheduled at investigator discretion, including to monitor 
open AE, or based on emerging data.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. If a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation in the study is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Chinese male and female participants aged 18 to 65 years of age, inclusive, at the 
time of signing the ICD.

All fertile participants must agree to use a highly effective method of 
contraception (Section 10.4.3 and Section 10.4.4).

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and 
female (Section 10.4.2) participants.
2. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, physical examination, standard 12-lead ECGs, 
and laboratory tests.
Other Inclusion Criteria: 
3. BMI of 19 to 27 kg/m2; and a total body weight >50 kg (110 lb). 
4. Capable of giving signed informed consent as described in Appendix 1: Regulatory, 
Ethical, and Study Oversight Considerations which includes compliance with 
requirements and restrictions listed in the ICD and in this protocol. 
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).

Any condition possibly affecting drug absorption (eg, gastrectomy, 
cholecystectomy).

History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, 
HBsAg, HCVAb or syphilis. Hepatitis B vaccination is allowed.
2. For hepatitis B, all participants must undergo testing for HBsAg, HBcAb, and 
HBsAb.

Participants who are negative for all 3 serology tests may be eligible.
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
Participants who are HBsAg positive will be excluded.

HBsAg negative, HBcAb positive, and HBsAb negative particpants are to be 
excluded from the study.

Participants who are HBsAg negative, HBcAb negative and HBsAb positive 
and provide documentation of prior HBV vaccination, may be eligible for the 
study and will not require HBVDNA monitoring during the study.

Participants who are HBsAg negative, HBcAb negative and HBsAb positive 
without documentation of prior HBV vaccination AND participants who are 
HBsAg negative, HBcAb positive, and HBsAb positive, will have HBV DNA 
assessed at screening.

If HBV DNA is detectable, participants will be excluded. 

If HBV DNA is not detectable, participants may be eligible. If the 
participant is included in the study, for subsequent visits HBVDNA testing 
must be performed according to the investigator’s guide.
3. Any medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality, or other conditions or situations 
related to COVID-19 pandemic that may increase the risk of study participation or, in 
the investigator’s judgment, make the participant inappropriate for the study.
Prior/Concomitant Therapy:
4. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention with the exception of moderate/strong CYP3A inducers or 
time-dependent inhibitors which are prohibited within 14 days plus 5 half-lives prior 
to the first dose of study intervention (refer to Section 6.9 for additional details).
Prior/Concurrent Clinical Study Experience:
5. Previous administration with an investigational product (drug or vaccine) within 
30 days (or as determined by the local requirement) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer). 
Diagnostic Assessments:
6. A positive urine drug test, confirmed by a repeat test, if deemed necessary.
7. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest. If BP is ≥ 140 mm Hg (systolic) or ≥90 mm Hg
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine the participant’s eligibility. 
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8. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTcF >450 ms, 
complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T 
interval changes suggestive of myocardial ischemia, second- or third- degree AV 
block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT 
interval is > 450 ms, this interval should be rate-corrected using the Fridericia method 
only and the resulting QTcF should be used for decision making and reporting. If 
QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice
and the average of the 3 QTcF or QRS values used to determine the participant’s 
eligibility. Computer-interpreted ECGs should be overread by a physician 
experienced in reading ECGs before excluding a participant.
9. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study--specific laboratory and confirmed by a single 
repeat test, if deemed necessary: 

GFR <80 mL/min/1.73m2 based on CKD-EPI equation;

AST or ALT level ≥1.05 × ULN; 

GGT > 1.05 × ULN; 

Alkaline phosphatase > 1.05 × ULN; 

Total bilirubin level ≥1.05 × ULN; participants with a history of Gilbert’s 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ULN.
Other Exclusion Criteria:
10. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 
5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, 
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
11. History of sensitivity to sisunatovir or any of the formulation components.
12. Use of tobacco or nicotine-containing products in excess of the equivalent of 
5 cigarettes/day or 2 chews of tobacco/day.
13. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
14. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
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delegate employees directly involved in the conduct of the study and their family 
members.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Contraception 
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant 
and their partner(s) from the permitted list of contraception methods (see Appendix 4,
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. 
At time points indicated in SoA, the investigator or designee will inform the participant of 
the need to use highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart. Participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception, 
considering that their risk for pregnancy may have changed since the last visit. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 
alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner.
5.3.2. Meals and Dietary Restrictions

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations and 10 hours prior to the collection of the predose 
PK sample.

Water is permitted until 1 hour prior to study intervention administration. Water may 
be consumed without restriction beginning 1 hour after dosing. Noncaffeinated drinks 
(except grapefruit or grapefruit-related citrus fruit juices—see below) may be 
consumed with meals and the evening snack.

No breakfast will be provided only on Day 1. On dosing days between Days 4-8, 
participants will consume a standard breakfast (non-high fat and high calorie, typical 
Chinese meal) approximately 30 minutes prior to dosing. On Day 4 and Day 8 (PK 
sampling days), the same standard breakfast will be provided and participants should 
be encouraged to complete their meals by approximately 10 minutes prior to 
anticipated dosing. On non dosing days, breakfast may be provided following the 
laboratory sample collection (as applicable). Only breakfast on Day 4 and Day 8 will 
be reported in the CSR. The following is an example of standard breakfast (typical 
Chinese meal, 699 kcal in total, 24% fat):
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
6 steamed dumplings (120 g flour, 40 g pork)

200 mL rice porridge (20 g rice)

1 egg (50 g)

Some pickles

Lunch will be provided approximately 4 hours after dosing.

Dinner will be provided approximately 11 to 13 hours after morning dosing.
Participants will receive the evening dose of study intervention 12 hours after the 
morning dose (plus or minus 1 hour) approximately 30 minutes after the start of a 
standard dinner that will be consumed over approximately 20 minutes.

An evening snack may be permitted.

Participants will refrain from consuming red wine, grapefruit, or grapefruit-related 
citrus fruits (eg, Seville oranges, pomelos, fruit juices) from 7 days prior to the first 
dose of study intervention until collection of the final PK blood sample. 

While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein. The daily caloric intake 
per participant should not exceed approximately 3200 kcal.
5.3.3. Caffeine, Alcohol, and Tobacco

Participants will abstain from caffeine-containing products for 24 hours prior to 
admission to the CRU and continue abstaining from caffeine-containing products 
during confinement in the CRU.

Participants will abstain from alcohol for 24 hours prior to admission to the CRU and 
continue abstaining from alcohol during confinement in the CRU. Participants may 
undergo an alcohol breath test at the discretion of the investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to admission to CRU and during confinement in the CRU. 
5.3.4. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted;
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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. Screen failure data are collected and remain as 
source and are not reported on the CRF.
Individuals who do not meet the criteria for participation in this study (screen failure) may
not be rescreened. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational and non-investigational medicinal 
products, medical devices, and other interventions (eg, surgical and behavioral) intended to 
be administered to the study participants during the study conduct.
For the purposes of this protocol, study intervention refers to sisunatovir.
6.1. Study Intervention(s) Administered
Study Intervention(s)
Intervention Name
PF-07923568 (sisunatovir)
Type
Drug
Use
Experimental
IMP or NIMP/AxMP
IMP
Dose Formulation
Capsule
Unit Dose Strength(s)
50 mg
Dosage Level(s)
Planned doses are 200 mg SD on Day 1 in a fasted state followed by repeated 
twice daily doses (Q12 hours) of 200 mg from Days 4-7 in a fed state, plus 1 
morning dose on Day 8 in a fed state.
Route of Administration
Oral
Sourcing
Provided centrally by the sponsor or locally by the trial site
Packaging and Labeling
Study intervention will be provided in bulk bottle along with individual 
dosing containers for unit dosing. 
Each bulk bottle will be labeled as required per country requirement.
Study intervention will be provided with open label at Bulk Bottle. CRU 
Staff will prepare individual doses for administration.
SRSD
IB
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Study Intervention(s)
Current/Former Name(s) or 
Alias(es)
Sisunatovir
PF-07923568
RV521
Study Arm(s)
Arm Title
Sisunatovir 200 mg
Arm Description
Participants will receive sisunatovir of 200 mg given as a single dose on Day 1 
in a fasted state followed by repeated twice daily doses (Q12 hours) from 
Days 4-7 in a fed state, plus 1 morning dose on Day 8 in a fed state.
Sisunatovir will be provided by Pfizer as 50-mg capsules at the CRU.
Capsules will be supplied to the CRU in bulk along with individual dosing containers for unit 
dosing.
6.1.1. Administration
On Day 1, participants will receive study intervention at approximately 0800 hours (plus or 
minus 2 hours). On Days 4-8, participants will receive study intervention at the similar time 
after the start of a typical Chinese breakfast that will be consumed over approximately 
20 minutes. Participants will receive the evening dose of study intervention 12 hours after the 
morning dose (plus or minus 1 hour) approximately 30 minutes after the start of a standard 
dinner that will be consumed over approximately 20 minutes. On Day 8, only the morning 
dose of study intervention will be administered. 
Investigator site personnel will administer study intervention during each period with 
ambient temperature water to a total volume of approximately 240 mL. Participants may 
receive additional ambient temperature water up to 100 mL, if needed. This will be 
documented by the site. Participants will swallow the study intervention whole, and will not 
manipulate or chew the study intervention prior to swallowing. If the participant spit out the 
drug, supplement is not allowed.
On Day 1, Day 4 and Day 8 for morning dose, in order to standardize the conditions on PK 
sampling days, all participants will be required to refrain from lying down (except when 
required for BP, pulse rate, and ECG measurements), eating, and drinking beverages other 
than water during the first 4 hours after dosing.
Administration of study intervention(s) at the site will be performed by an appropriately 
qualified and trained member of the study staff as allowed by local, state, and institutional 
guidance. 
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Following administration of study intervention(s) at the site, participants will be observed by 
an appropriately qualified and trained member of the study staff. Appropriate medication and 
other supportive measures for management of a medical emergency will be available in 
accordance with local guidelines and institutional guidelines.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions (eg, 
temperature) have been maintained during transit for all study interventions received 
and any discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention.
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized site staff. At 
a minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented upon 
return to business.
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to the labeled storage conditions, 
as soon as possible. Once an excursion is identified, the study intervention must be 
quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the excursion definition and information to
report for each excursion will be provided to the site in the CRU procedures.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label..
6. Study interventions should be stored in their original containers.
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records), such as the IPAL or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the CRU’s procedures. All destruction must be 
adequately documented. If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
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applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IPM.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff. Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol. Local health authority regulations or investigator 
site guidelines may use alternative terms for these activities.
Capsules will be prepared at the CRU in the individual dosing containers by 2 operators, 1 of 
whom is an appropriately qualified and experienced member of the study staff (eg, physician, 
nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist). 
The capsules will be provided in unit dose containers and labeled in accordance with Pfizer 
regulations and the clinical site’s labeling requirements. 
6.3. Assignment to Study Intervention
This is a non-randomized, single-arm study. All eligible participants will receive the same 
treatment. Following completion of informed consent at the screening visit, each participant 
will be assigned a participant number by the site staff. Each participant who is dosed with 
study intervention will also be assigned a separate, distinct number (as provided to the site by 
the sponsor), to enable execution of the sponsor’s standard processes for analysis of PK 
samples.
6.4. Blinding
This is an open-label study.
6.5. Study Intervention Compliance
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second qualified member of the study site staff.
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. Study site personnel will examine each participant’s mouth to ensure that 
the study intervention was ingested.
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6.6. Dose Modification
Dose modification is not allowed in this study.
6.7. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
6.8. Treatment of Overdose
Any single dose of sisunatovir greater than 300 mg or a daily dose greater than 600 mg 
within a 24-hour period will be considered an overdose.
There is no specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the study medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities as 
medically appropriate and follow up until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis if requested by the study medical monitor 
(determined on a case-by-case basis).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the study medical monitor as needed based on the clinical evaluation of the 
participant.
6.9. Prior and Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤1 g/day.
Females using hormonal contraceptives or taking hormone replacement therapy may be 
eligible to participate in this study if they are willing to discontinue therapy at least 28 days 
prior to the first dose of study treatment and remain off hormonal therapy for the duration of 
the study. Depo-Provera® must be discontinued at least 6 months prior to the first dose of 
study treatment.
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All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following:

AE requiring discontinuation in investigator’s view;

Pregnancy.
If study intervention is permanently discontinued, the participant will not remain in the study 
for further evaluation. See the SoA for data to be collected at the time of discontinuation of 
study intervention.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, further study follow-up, and/or 
future collection of additional information.
7.1.1. Potential Cases of Acute Kidney Injury
Participants exposed to IMP demonstrating transient or sustained increase in Screat (with 
decrease in Screat-based eGFR or eCrCl) require expedited evaluation to differentiate AKI 
from DICI. DICI is defined as transporter-mediated effect related to altered renal tubular 
creatinine handling without histological injury.
AKI may be due to one or more types of injury, including DIKI. Differentiation of DIKI 
from other causes of AKI and from DICI may require clinical, radiographic, histopathologic, 
and laboratory assessments, as well as nephrology consultation.
Follow-up Assessments
The participant should return to the site for evaluation as soon as possible, preferably within 
48 hours of awareness of the abnormal results. 
Evaluation should include physical examination, laboratory tests, detailed medical and 
surgical history, review of all medications (including recreational drugs and supplements 
[herbal]), family history, sexual history, travel history, blood transfusion, and potential 
occupational exposure to chemicals. 
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Laboratory assessments should include simultaneous serum cystatin C (Scys) and serum 
creatinine (Screat) tests. Estimates of eGFR, eCrCl and Screat-based eGFR and combined 
Screat-Scys-based eGFR should also be derived using the appropriate equation described in 
Appendix 7.
Assessments of urine albumin-to-creatinine ratio or urine volume may also be performed as 
appropriate.
If appropriate, nephrology consultation may be recommended to facilitate differentiation of 
renal parenchymal disease, pre-renal azotemia, and post-renal obstruction. 
If appropriate, nephrology consultation may be recommended to facilitate differentiation of 
renal parenchymal disease, pre-renal azotemia, and post-renal obstruction. 
Differentiating Acute Kidney Injury from DICI
A confirmed Screat increase is defined as:
(i) ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours OR 
(ii) confirmed Screat increase ≥1.5 times baseline (known or suspected to have occurred 
within the prior 7 days). 
Based on the assessments performed, suspected AKI (including DIKI) may be differentiated
from DICI as follows.
Adult participants
AKI (including DIKI)
Any one of the below
DICI
Scys & Screat
Simultaneous, confirmed serum cystatin 
C (Scys) increase and confirmed Screat 
increase 
Confirmed Screat increase without 
confirmed increase in reflex Scys 
AND 
Confirmed Screat-based eGFR 
decrease without confirmed combined 
Screat-Scys-based eGFR decrease.
eGFR
Decrease in Screat-based eGFR and 
combined Screat-Scys-based eGFR (when 
available)
Albuminuria or 
proteinuria
Confirmed albuminuria increase (see 
Appendix 6 for Grades A1 to A3 
quantitation)
Urine volume
Urine volume <0.5 mL/kg/h for 6 
consecutive hours
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Regardless of the presence or absence of increase in Screat, DIKI and other causes of AKI 
may be suspected if either there is (i) new-onset or worsening albuminuria or proteinuria are 
detected or (ii) urine volume (if measured) is <0.5 mL/kg/h for 6 consecutive hours).
All confirmed cases of clinically relevant decrease in kidney function should be considered 
potential cases of DIKI if no other reason for the kidney function abnormalities has been 
found.
7.1.2. Liver Injury 
A participant who meets the criteria of potential DILI (Hy’s law) case as described in 
Appendix 5 in Section 10.5 will be withdrawn from the study intervention.
7.1.3. ECG Changes 
A participant who meets either bulleted criterion based on the average of ECG readings will 
be withdrawn from the study intervention. 

QTcF >500 ms.

Change from baseline: QTcF >60 ms.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE.
7.1.4. COVID-19 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE (as 
appropriate) and appropriate medical intervention provided. Temporary discontinuation of 
the study intervention may be medically appropriate until the participant has recovered from 
COVID-19. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;
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
Study terminated by sponsor;

Pregnancy;

Behavioral, compliance, or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1 for 
disclosure of future information, no further evaluations will be performed and no additional 
data will be collected. The sponsor may retain and continue to use any data collected before 
such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
the participant is alive or dead) is being measured, publicly available information should be 
used to determine vital status only as appropriately directed in accordance with local law.
7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
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The following actions must be taken if a participant fails to attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative and Baseline Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
A participant who qualified for this protocol but did not enroll from an earlier cohort/group 
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, may not need to be repeated, as 
appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
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circumstances outside the control of the investigator that make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants for PK assessment in this study 
is approximately 115 mL. The other blood sampling for safety or other assessments should 
be collected according to the SoA, and the actual volume will depend on the clinical practice 
in the CRU. The total blood sampling volume for individual participants in this study will be
described in the informed consent. The actual collection times and volumes of blood 
sampling may change. Additional blood samples may be taken for safety assessments at 
times specified by Pfizer, provided the total volume taken during the study does not exceed 
550 mL during any period of 56 consecutive days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1.1. Baseline Procedures 
Planned timepoints for medical history and demography are provided in the SoA.
8.2. Efficacy Assessments
Efficacy parameters are not evaluated in this study. 
8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
8.3.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, gastrointestinal systems, and participant-reported 
symptoms.
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Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
Physical examination findings collected during the study will be considered source record 
and will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.4.1 to 8.4.3.
8.3.2. Chest Radiography
Chest X-ray (posterior-anterior and lateral views are recommended, however local guidelines 
should be followed) or other appropriate diagnostic image (ie, CT or MRI) should be taken at 
Screening or within 3 months prior to Screening and read by a qualified radiologist or 
pulmonologist and must show no evidence of abnormalities including but not limited to 
current, active TB or previous inactive TB, general infections, heart failure or malignancy. 
Documentation of the official reading must be located and available in the source document.
8.3.3. Vital Signs
8.3.3.1. Blood Pressure and Pulse Rate
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
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8.3.3.2. Temperature
Temperature (eg, ear temperature) will be measured according to local practice at time 
specified in the SoA. No eating, drinking, or smoking is allowed for 15 minutes prior to the 
measurement.
8.3.4. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) will be collected 
at times specified in the SoA section of this protocol using an ECG system that automatically 
calculates the HR and measures PR, QT, QTcF, and QRS intervals. All scheduled ECGs 
should be performed after the participant has rested quietly for at least 5 minutes in a supine 
position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements. Additional ECG monitoring will occur if a) a 
postdose QTcF interval is increased by ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG. If either of these conditions occurs, 
then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to confirm the 
original measurement. If the QTcF values from these repeated ECGs remain above the 
threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTcF interval remains ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG for greater than 4 hours (or sooner, at 
the discretion of the investigator); or c) QTcF value get progressively longer, the participant
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTcF
values do not return to less than the criteria listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.3.5. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
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The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition.
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within 48 hours after the last dose of study intervention should 
be repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or study medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
DILI.
See Appendix 6 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities.
Participants may undergo random urine drug testing at the discretion of the investigator. 
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.3.6. COVID-19 Specific Assessments
Testing for active COVID-19 infection, including testing methodology and frequency will 
follow CRU’s practice at scheduled times listed in the SoA. These tests may not be needed if 
the pandemic is over.
8.3.7. Pregnancy Testing
A urine or serum pregnancy test is required at screening. Following screening, pregnancy 
tests may be urine or serum tests, and must have a sensitivity of at least 25 mIU/mL. 
Pregnancy tests will be performed in WOCBP at the times listed in the SoA. Following a 
negative pregnancy test result at screening, appropriate contraception must be commenced 
and a second negative pregnancy test result will be required at the baseline visit prior to 
starting the study intervention. Pregnancy tests will also be done whenever 1 menstrual cycle 
is missed during the active treatment period (or when potential pregnancy is otherwise 
suspected) and at the end of the study. Pregnancy tests may also be repeated if requested by 
IRBs/ECs or if required by local regulations. If a urine test cannot be confirmed as negative 
(eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant 
must be excluded if the serum pregnancy result is positive.
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8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant/legally 
authorized representative will be questioned about the occurrence of AEs in a nonleading 
manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before undergoing any study-related procedure and/or receiving study 
intervention), through and including a minimum of 28 calendar days, except as indicated 
below, after the last administration of the study intervention.
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
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Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has conducted the study participation, and 
they consider the event to be reasonably related to the study intervention, the investigator 
must promptly report the SAE to Pfizer using the CT SAE Report Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available.
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
All nonserious AEs leading to permanent discontinuation of study intervention and SAEs (or 
additional AEs as required by regulatory authorities) occurring in a participant during the 
active collection period which begins after obtaining informed consent as described in 
Section 8.4.1, will be recorded on the AE section of the CRF. 
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs leading to permanent discontinuation of study intervention and SAEs reported by the 
participants that meet the above criteria.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE leading to 
permanent discontinuation of study intervention that is determined by the sponsor to be 
serious will be reported by the sponsor as an SAE. To assist in the determination of case 
seriousness, further information may be requested from the investigator to provide clarity and 
understanding of the event in the context of the clinical study.
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If a participant begins a new therapy, the recording period for nonserious AEs leading to 
permanent discontinuation of study intervention ends at the time the new treatment is started; 
however, SAEs must continue to be recorded on the CRF during the above-indicated active 
collection period. A switch to a commercially available version of the study intervention is 
considered as a new therapy for the purposes of SAE reporting.
Reporting of AEs leading to permanent discontinuation of study intervention and SAEs for 
participants who fail screening are subject to the CRF requirements as described in 
Section 5.4.
8.4.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.4.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3.
8.4.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
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An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure, occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.4.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention
inseminates a female partner until the follow-up visit (28-35 days after last dose of 
study intervention).

A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then inseminates his female 
partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or participant’s partner, the investigator must report 
this information to Pfizer Safety using the CT SAE Report Form and EDP 
Supplemental Form regardless of whether an SAE has occurred. Details of the 
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pregnancy will be collected after the start of study intervention and until the 
follow-up visit (28-35 days after last dose of study intervention) for the participant.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed report is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial report. In the case of a live birth, the structural integrity of the neonate 
can be assessed at the time of birth. In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion should be reported 
as an SAE;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if:

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
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
A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion, inhalation, or skin contact. 
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When EDB occurs in the setting of environmental exposure, 
the exposure information does not pertain to the participant enrolled in the study, so the 
information is not recorded on a CRF. However, a copy of the completed report is 
maintained in the investigator site file.
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 24 
hours of the investigator’s awareness using the CT SAE Report Form regardless of whether 
there is an associated SAE. Since the information about the occupational exposure does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed report is maintained in the investigator site file.
8.4.6. Cardiovascular and Death Events
Not applicable.
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.4.8. Adverse Events of Special Interest
Not applicable.
8.4.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.4.9. Medical Device Deficiencies
Not applicable.
8.4.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
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Medication errors are recorded and reported as follows:
Recorded on the 
Medication Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the medication error
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Other examples include, but are not limited to:

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;

The administration of study intervention that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, such medication errors occurring to a study participant are recorded on the 
medication error page of the CRF, which is a specific version of the AE page and, if 
applicable, any associated serious and nonserious AE(s), are recorded on the AE page of the 
CRF.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. Pharmacokinetics 
Whole Blood samples (approximately 3 mL) to provide approximately of 1 mL plasma, will 
be collected for measurement of plasma concentrations of sisunatovir as specified in the SoA. 
A whole blood aliquot (approximately 200 µL) from the PK blood draw only will be 
collected for in vivo blood/plasma ratio assessment on Day 4 and time points as specified in 
the SoA. Exploratory micro-sampling PK samples for the measurement of sisunatovir 
concentrations will be collected, in order to evaluate micro-sampling approach using the 
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Tasso® device. Total blood volume for micro-sampling PK will not exceed 0.1 mL at each 
time point specified in the SoA. Instructions for the collection and handling of biological 
samples will be provided in the laboratory manual or by the sponsor. The actual date and 
time (24-hour clock time) of each sample will be recorded.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to samples 
to be collected more than 10 hours after dose administration at outpatient/follow-up visits 
with visit windows.
Samples will be used to evaluate the PK of sisunatovir. Samples collected for analyses of
sisunatovir plasma concentration may also be used to evaluate safety or efficacy aspects 
related to concerns arising during or after the study, for metabolite identification and/or 
evaluation of the bioanalytical method. The data may be used for internal exploratory 
purposes. The exploratory results may not be reported in the CSR.
Genetic analyses will not be performed on these PK samples. Participant confidentiality will 
be maintained.
Samples collected for measurement of plasma concentrations of sisunatovir will be analyzed 
using a validated analytical method in compliance with applicable SOPs.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.6. Genetics
8.6.1. Specified Genetics
Specified genetic analyses are not evaluated in this study.
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8.6.2. Retained Research Samples for Genetics
Retained research samples for genetics will not be collected for this study.
8.7. Biomarkers
Biomarkers are not evaluated in this study.
8.8. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
There is no statistical hypothesis for this study.
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis 
Set
Description
Enrolled 
“Enrolled” means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process and 
assignment to study intervention.
PK Concentration 
Analysis Set
The PK concentration analysis set is defined as all participants 
who take at least 1 dose of study intervention and in whom at 
least 1 plasma concentration value is reported.
PK Parameter Analysis 
Set
The PK parameter analysis set is defined as all participants 
who take at least 1 dose of study intervention and have at least 
1 of the PK parameters of interest calculated.
Safety analysis set
All participants who take at least 1 dose of study intervention.
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9.3. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the analyses 
and procedures for accounting for missing, unused, and spurious data. This section is a 
summary of the planned statistical analyses of the primary and secondary endpoints.
9.3.1. Pharmacokinetic Analyses
9.3.1.1. Statistical Methods for Pharmacokinetic Data
The plasma PK parameters of sisunatovir will be listed and descriptively summarized by 
study day. For AUClast, AUCinf, AUCtau, and Cmax, box and whisker plots for individual 
participant parameters overlaid with geometric means will be plotted. The PK parameter 
analysis set will be used.
The plasma concentrations of sisunatovir will be listed and descriptively summarized by 
study day and nominal PK sampling times. Individual participant and summary profiles 
(mean and median plots) of the plasma concentration-time data will be plotted using actual 
and nominal sampling times, respectively. The PK concentration analysis set will be used.
Concentrations of sisunatovir obtained via microsampling from paired samples compared to 
plasma sampling will be summarized by sampling time on Day 4 and be listed if possible.
Additional specifications about the tables, listings, and figures will be outlined in the SAP.
9.3.1.2. Derivation of Pharmacokinetic Parameters Prior to Analysis
The plasma PK parameters for sisunatovir, following single dose in a fasted state and 
repeated twice daily doses in a fed state, will be derived from the plasma concentration-time 
profiles as detailed in Table 4, as data permit. Actual PK sampling times will be used in the 
derivation of PK parameters. In the case that actual PK sampling times are not available, 
nominal PK sampling times will be used in the derivation of PK parameters.
Table 4.
Plasma PK Parameters for Sisunatovir
Parameter
Study 
Day 
Definition
Method of Determination
Cmax
1, 4, 8
Maximum observed concentration
Observed directly from data
Tmax
1, 4, 8
Time to reach maximum 
concentration
Observed directly from data
AUCinfa
1, 8
Area under the concentration-time 
curve from time 0 to infinity
AUClast + (Clast/kel),
where Clast is the predicted plasma
concentration at the last quantifiable time 
point estimated from the log-linear 
regression analysis
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Table 4.
Plasma PK Parameters for Sisunatovir
Parameter
Study 
Day 
Definition
Method of Determination
AUClast
1, 8
Area under the concentration-time 
curve from time 0 to the time of 
last quantifiable concentration
Linear/Log trapezoidal method
AUCtau
1, 4, 8
Area under the concentration time 
curve from time 0 to the time of 
the end of the dosing interval (tau), 
where tau=12 hours
Linear/Log trapezoidal method.
t½a
1, 8
Terminal half-life
Loge(2)/kel, where kel is the terminal
phase rate constant calculated by a linear 
regression of the log-linear
concentration-time curve
MRTa
1, 8
Mean residence time
Day 1: MRT = AUMCinf/AUCinf
Day 8: [AUMCtau + tau(AUCinf-
AUCtau)]/AUCtau
where AUMCinf is the area under the first 
moment curve from zero time to infinity
AUMCtau is area under the first moment 
curve over the dosing interval tau.
Vz/Fa
1
Apparent volume of distribution
Dose/(AUCinf × kel)
CL/Fa
1, 8
Apparent oral clearance
Dose/AUCinf
Raca
8
Accumulation ratio on AUCtau
AUC12 (Day 8) /AUC12 (Day 4)
Rac,Cmaxa
8
Accumulation ratio on Cmax
Cmax (Day 8) /Cmax (Day 4)
Ctrough
6, 7, 8
Lowest concentration observed 
during the dosing interval 
Observed directly from data
Cav
8
Average concentration at steady 
state 
AUC12 (Day 8) /12 hours.
Vz/Fa
8
Apparent volume of distribution at 
steady state 
Vz/F = Dose/(AUCtau × kel)
PTR
8
Peak-trough ratio
Cmax/Ctrough
a. If data permit.
 
 
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9.3.2. Safety Analyses
All safety analyses will be performed on the safety analysis set.
AEs, ECGs, vital signs, and safety laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of participants. Any clinical laboratory, 
ECG, vital signs abnormalities of potential clinical concern will be described. Safety data 
will be presented in tabular and/or graphical format and summarized descriptively, where 
appropriate.
Medical history and physical examination collected during the course of the study, will be 
considered source data and will not be required to be reported, unless otherwise noted. 
However, any untoward findings identified on physical examinations conducted during the 
active collection period will be captured as AEs, if those findings meet the definition of an 
AE. Data collected at screening that are used for inclusion/exclusion criteria, such as 
laboratory data, ECGs, and vital signs, will be considered source data, and will not be 
required to be reported, unless otherwise noted. Demographic data collected at screening will 
be reported.
9.3.2.1. Electrocardiogram Analyses
Baseline and changes from baseline for the ECG parameters (ie, HR, QT, QTcF interval, PR 
interval, and QRS interval) will be summarized by study day.
The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories will be tabulated: 
Safety QTcF Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
9.4. Interim Analyses
No interim analysis will be conducted for this study. 
9.5. Sample Size Determination
There is no statistical hypothesis for this study, therefore, the study sample size is not based 
on statistical decision rule. A sufficient number of participants will be screened to achieve 
approximately 12 Chinese participants being available for deriving PK parameters. This
sample size is based on the China regulatory requirement for a China PK study and to 
support the registration in China. Participants who fail to complete the study may be replaced 
at the discretion of the sponsor and investigator. 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies, European Medical Device Regulation 2017/745 for 
clinical device research, and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and sub investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant/legally authorized representatives and 
answer all questions regarding the study. The participant should be given sufficient time and 
opportunity to ask questions and to decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each participant is fully informed about the nature and 
objectives of the study, the sharing of data related to the study, and possible risks associated 
with participation, including the risks associated with the processing of the participant’s 
personal data. 
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about their
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
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A copy of the ICD(s) must be provided to the participant.
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 28 days from the previous ICD signature date.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains SOPs on how to respond in the event of unauthorized access, use, or 
disclosure of sponsor information or systems.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will not use an E-DMC.
10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized.
Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
18 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
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responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source records and documents.
This verification may also occur after study completion. It is important that the 
investigator(s) and their relevant personnel are available during the monitoring visits and 
possible audits or inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
In this study, the CRF will serve as the source document. A document must be available at 
the investigative site that identifies those data that will be recorded on the CRF and for which 
the CRF will be the source document.
Definition of what constitutes a source document and its origin can be found in the Source 
Document Locator, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source record) that supports the 
information entered in the CRF.
10.1.9. Use of Medical Records
There may be instances when copies of medical records for certain cases are requested by 
Pfizer Safety, where ethically and scientifically justified and permitted by local regulations, 
to ensure participant safety.
Due to the potential for a participant to be re-identified from their medical records, the 
following actions must be taken when medical records are sent to the sponsor or sponsor 
designee:

The investigator or site staff must redact personal information from the medical 
record. The personal information includes, but is not limited to, the following:  
participant names or initials, participant dates (eg, birth date, date of hospital 
admission/discharge, date of death), participant identification numbers (eg, Social 
Security number, health insurance number, medical record number, 
hospital/institution identifier), participant location information (eg, street address, 
city, country, postal code, IP address), participant contact information (eg, 
telephone/fax number, email address).

Each medical record must be transmitted to the sponsor or sponsor designee using 
systems with technical and organizational security measures to ensure the protection 
of personal data (eg, Florence is the preferred system if available). 
There may be unplanned situations where the sponsor may request medical records (eg, 
sharing medical records so that the sponsor can provide study-related advice to the 
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investigator). The medical records should be submitted according to the procedure described 
above.
10.1.10. Study and Site Start and Closure
The study start date is the date of the first participant’s first visit.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or CRO if requested to do so by the responsible IRB/EC or if such termination is required to 
protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor’s procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.11. Publication Policy
For multicenter trials, the primary publication will be a joint publication developed by the 
investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. 
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study.
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Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section.
The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. If any patent action is required to protect intellectual property rights, the 
investigator agrees to delay the disclosure for a period not to exceed an additional 60 days 
upon request from Pfizer. This allows Pfizer to protect proprietary information and to provide 
comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study-intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
study results. For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication.
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.12. Sponsor’s Medically Qualified Individual
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the supporting study documentation.
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from non-study healthcare professionals, participants are provided 
with an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol 
and study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center 
number.
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. The Pfizer Call Center number is to be used when the investigator and site staff 
are unavailable. The Pfizer Call Center number is not for use by the participant directly; if a 
participant calls that number directly, they will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values; for example: calculation of estimated kidney function (ie, 2021 
CKD-EPI eGFR). These additional tests would not require additional collection of blood. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
Table 5.
Protocol-Required Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN (Urea)
Creatinine
Cystatin Ca
eGFRb
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
GGT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Local dipstick:
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase 
(leukocyte)
Urobilinogen
Urine bilirubin
Laboratory:
Microscopy and 
culturec
At screening:

FSHd

Alcohol breath test

HIV, HBsAg, HBcAb, 
HBsAb, HCVAb

Serology reaction of 
syphilis test

HBV-DNA

Pregnancy test (β-hCG)a
Screening and as indicated

Urine albumin-to-
creatinine-ratio (UACR)

Urine drug screeninge

Urine pregnancy testf

COVID-19 test
a.
Cystatin C (Scys): Screening or Baseline Scys is recommended to help differentiate post-baseline DIKI 
from DICI. Post-baseline, Scys is measured if and only if serum creatinine increase post-baseline is 
observed (see Section 7.1.1).
b.
Screening and Baseline eGFR is measured with Screat-based formula. Age-specific kidney function 
calculation (see Section 10.6.2) is recommended to assess presence or absence of post-baseline change in 
kidney function.
c.
Only if UTI is suspected and urine dipstick is positive for nitrites or leukocyte esterase or both.
d.
For confirmation of postmenopausal status only in females <60 years old and not using hormonal or 
HRT only.
e.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/EC. See SoA for collection times.
f.
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, benzodiazepines, 
and amphetamines (others are site- and study-specific). See SoA for collection times.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or 
not considered related to the study intervention.

Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Any 
abnormal test results that meet any of the conditions below must be recorded as 
an AE:

Is associated with accompanying symptoms;

Requires additional diagnostic testing or medical/surgical intervention;

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition, including an 
increase in either frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration,
even though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms 
of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event that hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
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d. Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic 
The event may be suspected from clinical symptoms or laboratory findings 
indicating an infection in a participant exposed to a Pfizer product. The terms 
“suspected transmission” and “transmission” are considered synonymous. These 
cases are considered unexpected and handled as serious expedited cases by 
pharmacovigilance personnel. Such cases are also considered for reporting as 
product defects, if appropriate.
g. Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs using the CT SAE Report Form/Vaccine SAE Report Form to Pfizer 
Safety throughout the active collection period. These requirements are delineated for 3 
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types of events: (1) SAEs; (2) nonserious AEs; and (3) exposure to the study 
intervention under study during pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form/Vaccine SAE Report Form for 
reporting of SAE information is not the same as the AE page of the CRF. When the 
same data are collected, the forms must be completed in a consistent manner. AEs 
should be recorded using concise medical terminology and the same AE term should be 
used on both the CRF and the CT SAE Report Form/Vaccine SAE Report Form for 
reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form/Vaccine 
SAE Report Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding
All AEs/SAEs associated 
with EDP or EDB
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)**
Environmental or 
occupational exposure 
to the product under 
study to a 
nonparticipant (not 
involving EDP or EDB)
None. Exposure to a study 
non-participant is not 
collected on the CRF
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported***
*
EDP (with or without an associated SAE): is reported to Pfizer Safety using the CT SAE Report 
Form and EDP Supplemental Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form, which would also include 
details of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 

When an AE or SAE occurs, it is the responsibility of the investigator to review 
all documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE or SAE information in the CRF.
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
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form /AE or SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. Refer to Section 10.1.9for actions 
that must be taken when medical records are sent to the sponsor or sponsor 
designee.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE or SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual ADL.

Moderate: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual ADL, causing 
discomfort, but poses no significant or permanent risk of harm to the research 
participant.

Severe: A type of AE that interrupts usual ADL, or significantly affects clinical 
status, or may require intensive therapeutic intervention.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out.
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
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for 
marketed products, in their assessment.

For each AE or SAE, the investigator must document in the medical notes that 
they have reviewed the AE or SAE and have provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the 
sponsor.

The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for 
reporting purposes, as defined by the sponsor. In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator 
must record this causal relationship in the source documents and CRF, and report 
such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations, as medically indicated or as 
requested by the sponsor, to elucidate the nature and/or causality of the AE or 
SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other 
healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.
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
New or updated information will be recorded in the originally submitted 
documents.

The investigator will submit any updated SAE data to the sponsor within 
24 hours of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic DCT

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic DCT (eg, eSAE or PSSA).

If the electronic system is unavailable, then the site will use the paper SAE report 
form (see next section) to report the event within 24 hours.

The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or 
paper form (as applicable) as soon as the data become available.

After the study is completed at a given site, the electronic DCT will be taken 
off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic DCT has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via the CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is one of the methods to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, an alternative method should 
be used, eg, secured (Transport Layer Security) or password-protected email. If 
none of these methods can be used, notification by telephone is acceptable with a 
copy of the CT SAE Report Form sent by overnight mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated 
reporting time frames.
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10.4. Appendix 4: Contraceptive and Barrier Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR

Must agree to use contraception/barrier as detailed below:

Agree to use a male condom, and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom 
may break or leak when having sexual intercourse with a WOCBP who is not 
currently pregnant.

In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of Inclusion Criterion 1 (Age and Sex; Section 5.1) and specify 
the reproductive requirements for including female participants. Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
A female participant is eligible to participate if she is not pregnant or breastfeeding and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definition in Section 10.4.3).
OR

Is a WOCBP and agrees to use a highly effective contraceptive method (failure rate of 
<1% per year) during the intervention period and for at least 28 days after the last 
dose of study intervention, which corresponds to the time needed to eliminate any 
reproductive safety risk of the study intervention(s). If a highly effective, 
user-dependent method is chosen, she agrees to concurrently use an effective barrier 
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method of contraception. The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea or oligomenorrhea) and a menstrual cycle cannot be 
confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to a medical cause other than the above
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be applied 
to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female.

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 

A female on HRT and whose menopausal status is in doubt will be required to 
use one of the highly effective nonestrogen hormonal contraception methods 
if she wishes to continue her HRT during the study. Otherwise, she must 
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discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
The following contraceptive methods are appropriate for this study:
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral + barrier*

Intravaginal + barrier*

Transdermal + barrier*
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral + barrier*

Injectable + barrier*
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8. Sexual Abstinence
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
* Acceptable barrier methods to be used concomitantly with options 6 or 7 for the study 
include any of the following:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods).
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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
LFTs are not required as a routine safety monitoring procedure in this study. However, 
should an investigator deem it necessary to assess LFTs because a participant presents with 
clinical signs/symptoms, such LFT results should be managed and followed as described 
below.
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be 
elevated within the same laboratory sample). In rare instances, by the time T bili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST OR ALT in addition to T bili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili value ≥2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR T bili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values ≥2 times the baseline values AND ≥3 × ULN; or ≥8 × ULN (whichever is 
smaller).
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
Preexisting values of T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller).
Rises in AST/ALT and T bili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, eosinophils (%), and alkaline phosphatase. Consideration should also be 
given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology. A detailed history, including relevant information, 
such as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, total bile acids, liver imaging (eg, biliary tract), and 
collection of serum samples for acetaminophen/paracetamol drug and/or protein adduct 
levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.6. Appendix 6: Kidney Safety: Monitoring Guidelines
10.6.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline Screat
measurement to estimate kidney function [Screat-based eGFR] or creatinine clearance 
[eCrCl]). Obtaining Screening or Baseline Scys and postbaseline reflex Scys (if confirmed 
Screat increase ≥0.3 mg/dL) makes it feasible to distinguish AKI from DICI. If Screat 
increase is confirmed after baseline, then reflex measurement of Scys is indicated:
ADULTS: Currently, 2021 CKD-EPI eGFR equations (Screat only-based and combined 
Screat plus Scys-based) are valid for use in adults only. At baseline Screat and Scys values 
are needed to calculate 2021 CKD-EPI eGFR by Screat only-based equation (see Table 
10.7.2.1.) and by combined Screat plus Scys-based equation. When post-baseline Screat 
increase ≥0.3 mg/dL is confirmed, then reflex Scys measurement is needed to enable
post-baseline comparison of eGFR changes (Screat only-based eGFR and combined Screat 
plus Scys eGFR). 
10.6.2. Age-Specific Kidney Function Calculation Recommendations
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
eGFR (mL/min/1.73m²)11
2021 CKD-
EPI          
Screat Only
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤0.7
NA
eGFR = 143 × (Screat/0.7)-0.241  ×  (0.9938)Age
Female
if > 0.7
NA
eGFR = 143 × (Screat/0.7)-1.200  ×  (0.9938)Age
Male
if ≤0.9
NA
eGFR = 142 × (Screat/0.9)-0.302  ×  (0.9938)Age
Male
if > 0.9
NA
eGFR = 142 × (Screat/0.9)-1.200  ×  (0.9938)Age
2021 CKD-
EPI          
Screat-Scys 
Combined
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤0.7
if ≤0.8
eGFR = 130 × (Screat/0.7)-0.219  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if ≤0.7
if > 0.8
eGFR = 130 × (Screat/0.7)-0.219  × (Scys/0.8)-0.778  × (0.9961)Age
Female
if > 0.7
if ≤0.8
eGFR = 130 × (Screat/0.7)-0.544  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if > 0.7
if > 0.8
eGFR = 130 × (Screat/0.7)-0.544  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if ≤0.9
if ≤0.8
eGFR = 135 × (Screat/0.9)-0.144  × (Scys/0.8)-0.323  × (0.9961)Age
Male
if ≤0.9
if > 0.8
eGFR = 135 × (Screat/0.9)-0.144  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if > 0.9
if ≤0.8
eGFR = 135 × (Screat/0.9)-0.544  ×  (Scys/0.8)-0.323  × (0.9961)Age
Male
if > 0.9
if > 0.8
eGFR = 135 × (Screat/0.9)-0.544  ×  (Scys/0.8)-0.778  × (0.9961)Age
10.6.3. Kidney Function Calculation Tools
The sponsor has provided the following resources to investigational sites when required to 
calculate age-specific kidney function at Screening, Baseline, and post-Baseline visits. Site 
calculations of kidney function can be performed manually, using the age appropriate 
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formulae (see Section 10.6.2) and can use recommended online kidney function calculators 
to reduce the likelihood of a calculation error. 
The United States National Kidney Foundation Online Calculators. 

Adults (18 years and above) - 2021 CKD-EPI Creatinine Online Calculator (eGFR): 
Investigational sites are responsible to ensure that the accurate age-specific equation is 
selected and that the correct units for serum creatinine (mg/dL only), serum cystatin C (mg/L 
only), total body weight (kg only), and age (years). Investigators are expected to (i) review 
and confirm correctness of the kidney function calculation results and (ii) evaluate the 
calculated value within the context of historical information available to them in the 
participant’s medical record. Investigators are responsible for the clinical oversight of the 
participant eligibility process, kidney function calculation, and dose selection and 
adjustments per study protocol. Investigators are encouraged to direct questions or 
uncertainties regarding kidney function and dosing to the Pfizer Clinical Team and Medical 
Monitor, if needed.
10.6.4. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to Kidney 
Disease: Improving Global Outcomes (KDIGO) criteria for both pediatric and adult 
participants.
KDIGO criteria
grade (G)
Study 
Population
G1
G2
G3
G4
G5
Decreased Kidney 
Function due to 
either Acute or 
Chronic Kidney 
Injury 
Adult 
participants
eGFR 
(mL/min/1.73m²)
≥90 
≥60 to 89
30 to 59 
15 to 29
<15
KDIGO albuminuria (A) 
criteria
A1
A2
A3
Albumin-to-creatinine 
ratio (ACR)
<30 mg/g
OR     
<3 mg/mmol 
30 to 300 mg/g
OR 
3 to 30 mg/mmol
>300 mg/g 
OR 
>30 mg/mmol
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 ms.

New prolongation of QTcF to >480 ms (absolute).

New prolongation of QTcF by >60 ms from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30-second duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 ms.

Absolute value of QTcF > 450 ms AND QTcF change from baseline >60 ms.

New ST-T changes suggestive of myocardial ischemia.

New-onset LBBB (QRS complex>120 ms).

New-onset right bundle branch block (QRS complex>120 ms).

Symptomatic bradycardia.

Asystole

In awake, symptom-free participants in sinus rhythm, with documented 
asystolic pauses ≥3 seconds or any escape rate <40 bpm, or with an escape 
rhythm that is below the AV node;

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more asystolic pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.
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
Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (HR
<40 bpm), accelerated idioventricular rhythm (HR >40 bpm to <100 bpm), and 
monomorphic/polymorphic ventricular tachycardia (HR >100 bpm [such as
torsades de pointes]).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as SAEs

Change in pattern suggestive of new myocardial infarction.

Sustained ventricular tachyarrhythmias (>30-seconds duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The major events of potential clinical concern listed above are recommended as “alerts” or notifications 
from the core ECG laboratory to the investigator and Pfizer study team, and not to be considered as all-
inclusive of what is to reported as AEs/SAEs.
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10.8. Appendix 8: Prohibited Concomitant Medications That May Result in DDI  
The prohibited concomitant medications listed below should not be taken with sisunatovir for 
the period of time at least equal to the required washout period listed in the table, and 
throughout the conduct of the study. 
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
After consulting with the sponsor, the investigator will make a judgment on the ongoing 
participation of any participant with prohibited medication use during the study.
This list of drugs prohibited for potential DDI concerns with the IMP may be revised during 
the course of the study with written notification from sponsor, to include or exclude specific 
drugs or drug categories for various reasons (eg, emerging DDI results for the IMP, 
availability of new information in literature on the DDI potential of other drugs), if the 
overall benefit: risk assessment is not impacted or if the changes do not significantly impact  
the safety of participants or the scientific value of the trial  
Strong and moderate CYP3A4 and P-gp inhibitors or inducers are prohibited, as these 
medications may have meaningful impact on the pharmacokinetics of sisunatovir.
Sisunatovir is a CYP3A4 inhibitor and therefore sensitive and narrow therapeutic index 
CYP3A4 substrates are also prohibited in this study.
Sisunatovir also may be an inhibitor of OCT1 and MATE1 transporters; therefore, sensitive 
substrates of these transporters are excluded.
This is not an all-inclusive list. Site staff should consult with the sponsor or designee with 
any questions regarding potential DDI.
Prohibited Concomitant Medications
CYP3A Inhibitors
CYP3A Inducers
Moderate
Strong
Moderate
Strong
Aprepitant
Boceprevir
Bosentan
Apalutamide
Ciprofloxacin
Cobicistat
Efavirenz
Carbamazepine
Conivaptan
Danoprevir
Etravirine
Enzalutamide
Crizotinib
Dasabuvir
Phenobarbital
Mitotane
Cyclosporine
Elvitegravir
Primidone
Phenytoin
Diltiazem
Indinavir
Rifampin
Dronedarone
Itraconazole
St. John’s wort
Erythromycin
Ketoconazole
Fluconazole
Lopinavir
Fluvoxamine
Paritaprevir
Imatinib
Ombitasvir
Tofisopam
Posaconazole
Verapamil
Ritonavir
Saquinavir
Telaprevir
Tipranavir
Telithromycin
Troleandomycin
Voriconazole
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Sensitive CYP3A Substrates
CYP3A Substrates 
with Narrow Therapeutic Index
Alfentanil
Lovastatin
Alfentanil
Atorvastatin
Lurasidone
Astemizole
Avanafil
Maraviroc
Cisapride
Budesonide
Midazolam
Cyclosporine
Buspirone
Naloxegol
Dihydroergotamine
Darifenacin
Nisoldipine
Ergotamine
Darunavir
Quetiapine
Fentanyl
Dasatinib
Sildenafil
Pimozide
Dronedarone
Simvastatin
Quinidine
Ebastine
Sirolimus
Sirolimus
Eletriptan
Tacrolimus
Tacrolimus
Eplerenone
Ticagrelor
Terfenadine
Everolimus
Tolvaptan
Ibrutinib 
Tipranavir
Indinavir
Triazolam
Felodipine
Vardenafil
Lomitapide
Sensitive MATE1 Substrates
Metformin
P-gp Inhibitors
P-gp Inducers
Atazanavir
Lopinavir
Apalutamide
Boceprevir
Lumacaftor
Atazanavir
Cobicistat
Mifepristone
Fosamprenavir
Conivaptan
Nelfinavir
Lopinavir
Cyclosporine
Ombitasvir and Paritaprevir 
and Ritonavir and 
Dasabuvir
Rifampicin
Darunavir
Posaconazole
st. John’s wort (Hypericum perforatum) extract
Diltiazem
Ritonavir
Tipranavir
Elvitegravir and Cobicistat 
and Emtricitabine and 
Tenofovir DF
Saquinavir
Verapamil
Erythromycin
Telaprevir
Glecaprevir and Pibrentasvir
Tipranavir
Indinavir
Tucatinib
Itraconazole
Verapamil
Ketoconazole
Vonoprazan and 
Amoxicillin and 
Clarithromycin
Lonafarnib
Voxilaprevir
Sensitive OCT Substrates
Imatinib
Not an all-inclusive list. 
Investigators should consult the product label for any other medication used during the study 
for information regarding medication that is prohibited for concomitant use. 
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10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
A1 to A3
albuminuria (KDIGO albuminuria severity standardization)
Abs
absolute
ADL
activity/activities of daily living
AE
adverse event
AKI
acute kidney injury
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the curve
AUC12
area under the concentration-time curve from time zero to 12 hours
AUC24
area under the concentration-time curve from time zero to 24 hours 
(1 day)
AUCinf
area under the concentration-time curve from time 0 to infinity
AUClast
area under the concentration-time curve from time 0 to the time of 
last quantifiable concentration
AUCtau
area under the concentration-time profile from time zero to time tau 
(the dosing interval), where tau = 12 hours for BID dosing
AV
atrioventricular
AxMP
auxiliary medicinal product
BID
twice-daily dosing
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
Cav
average concentration at steady state
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
chronic kidney disease epidemiology
CL/F
apparent clearance
Cmax
maximum observed plasma concentration
CO2
carbon dioxide (bicarbonate)
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
clinical trial
CTIS
Clinical Trial Information System
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Abbreviation
Term
Ctrough
lowest concentration observed during the dosing interval
CV
Cardiovascular/coefficient of variation
CYP
cytochrome P450
DCT
data collection tool
DDI
drug-drug interaction 
DIC
drug in capsule
DILI
drug-induced liver injury
DPB
sisunatovir dry powder blend
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram or electrocardiography
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
EDB
exposure during breastfeeding
E-DMC
External Data Monitoring Committee
EDP
exposure during pregnancy
EGFR
epidermal growth factor receptor
eSAE
electronic serious adverse event
ET
early termination
EU
European Union
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database)
FDA
Food and Drug Administration
FIH
first in human
FSH
follicle-stimulating hormone
F/U
follow-up
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GI
gastrointestinal 
HBcAb
hepatitis B core antibody
HbsAb
hepatitis B surface antibody
HbsAg 
hepatitis B surface antigen
HBP cyclodextrin
hydroxypropyl-β-cyclodextrin
HCVAb
hepatitis C antibody
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure
IBC
isobutyl carnitine
ICD
informed consent document
ICH
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use
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Abbreviation
Term
ICU
intensive care unit
ID
identification
IMP
investigational medicinal product
IND
Investigational New Drug 
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IPM
investigational product manual
IRB
Institutional Review Board
IV
intravenous(ly)
K
Proportionality constant for Bedside and Modified Schwartz 
Equations (kidney function)
KDIGO
Kidney Disease Improving Global Outcomes
LBBB
left bundle branch block
LFT
liver function test
LRTI
lower respiratory tract infection
MAD
multiple ascending dose
MATE
multidrug and toxin extrusion
MQI
medically qualified individual
MRT
mean residence time
MTD
maximum tolerated dose
NA
not applicable/not available
NIMP
noninvestigational medicinal product
NMN
N1-METHYLNICOTINAMIDE
NOAEL
no-observed-adverse-effect level
OAT
organic anion transporting 
OATP
organic anion transporting polypeptide
OCT
organic cation transporter
PD
pharmacodynamic(s)
PE
physical examination
P-gp
p-glycoprotein
PI
principal investigator
PIMS
Phase One Management System
PK
pharmacokinetic(s)
PR
pulse rate
PSSA
Pfizer's Serious Adverse Event Submission Assistant
PT
prothrombin time
PTR
peak-trough ratio
PVC
premature ventricular contraction/complex
Q12
every 12 
QTc
corrected QT interval
QTcF
QTc corrected using Fridericia’s formula
qual
qualitative
Rac
observed accumulation ratio for AUC
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Abbreviation
Term
Rac,Cmax
observed accumulation ratio for Cmax
RBC
red blood cell
RSV
respiratory syncytial virus
SAD
single ascending dose
SADE
serious adverse device effect
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
Scr
serum creatinine
Scys
serum cystatin C
SD
single dose
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
Single Reference Safety Document
SUSAR
Suspected Unexpected Serious Adverse Reaction
t½
terminal elimination half-life
TB
tuberculosis 
T bili
total bilirubin
TEAE
treatment emergent adverse event
THC
tetrahydrocannabinol
Tmax
time to reach Cmax
UACR
urine albumin/creatinine ratio
ULN
upper limit of normal
US
United States
Vz/F
apparent volume of distribution
WBC
white blood cell
WOCBP
woman/women of childbearing potential
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11. REFERENCES
1
Simoes EAF, Bont L, Manzoni P, et al. Past, Present and Future Approaches to the 
Prevention and Treatment of Respiratory Syncytial Virus Infection in Children. Infect 
Dis Ther. 2018;7(1):87-120.
2
Li Y, Wang X, Blau DM, et al. Global, regional, and national disease burden estimates 
of acute lower respiratory infections due to respiratory syncytial virus in children 
younger than 5 years in 2019: a systematic analysis. Lancet. 2022;399(10340):2047- 64.
3
Rha B, Curns AT, Lively JY, et al. Respiratory Syncytial Virus-Associated 
Hospitalizations Among Young Children: 2015-2016. Pediatrics. 
2020;146(1):e20193611.
4
Langley JM, Bianco V, Domachowske JB, et al. Incidence of Respiratory Syncytial 
Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A 
Prospective Study Across Diverse Global Settings. J Infect Dis. 2022;226(3):374-85.
5
Kim L, Rha B, Abramson JS, et al. Identifying Gaps in Respiratory Syncytial Virus 
Disease Epidemiology in the United States Prior to the Introduction of Vaccines. Clin 
Infect Dis. 2017;65(6):1020-5.
6
Jha A, Jarvis H, Fraser C, Openshaw PJM. Respiratory Syncytial Virus. In: Hui DS, 
Rossi GA, Johnston SL, eds. SARS, MERS and other Viral Lung Infections. Sheffield 
(UK)2016.
7
Kim L, Rha B, Abramson JS, et al. Identifying Gaps in Respiratory Syncytial Virus 
Disease Epidemiology in the United States Prior to the Introduction of Vaccines. Clin 
Infect Dis. 2017;65(6):1020-1025.
8
SYNAGIS (palivizumab). US Prescription Information (USPI); Mar 2014, Gaithersburg,
MD: MedImmune, LLC. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/103770s5185lbl.pdf. 
Accessed on: 23 Mar 2023.
9
SYNAGIS (palivizumab) SmPC. EPAR product information: EMA. Available from: 
https://www.ema.europa.eu/en/documents/product-information/synagis-epar-product-
information_en.pdf. Accessed on: 23 Mar 2023.
                                                
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10
BEYFORTUS (nirsevimab) SmPC. EPAR product information: EMA. Available from: 
https://www.ema.europa.eu/en/documents/product-information/beyfortus-epar-product-
information_en.pdf. Accessed on: 13 Apr 2023.
11
Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based 
Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-49.
090177e19db065aa\Approved\Approved On: 12-Jun-2023 02:20 (GMT)

SAP_001.pdf: 
Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 of 1 7
Pr ot oc ol C 5 2 4 1 0 1 8
A P H A S E 1, O P E N -L A B E L, SI N G L E - A R M S T U D Y T O E V A L U A T E T H E 
P H A R M A C O KI N E TI C S, S A F E T Y, A N D T O L E R A BI LI T Y F O L L O WI N G SI N G L E A N D 
M U L TI P L E D O S E S O F SI S U N A T O VI R I N C HI N E S E H E A L T H Y P A R TICI P A N T S
St atistic al A n al ysis Pl a n 
( S A P)
Versi o n :
1 . 0
D ate:
0 8 A u g 2 0 2 3   
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 of 1 7
T A B L E O F C O N T E N T S
LI S T O F T A B L E S ..................................................................................................................... 3
1. V E R SI O N HI S T O R Y ............................................................................................................ 4
2. I N T R O D U C TI O N ................................................................................................................. 4
2. 1. M o dificati o ns t o t he A nal y sis Plan Descri be d i n t he Pr ot oc ol .................................. 4
2. 2. St u d y  O bjecti ves, E n d p oi nts, a n d Esti ma n ds............................................................ 4
2. 3. St u d y  Desi g n............................................................................................................. 5
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S .................................................................................................................. 6
3. 1. Pri mar y  E n d p oi nt(s).................................................................................................. 6
3. 2. Sec o n dar y  E n d p oi nt(s).............................................................................................. 6
3. 3. Ot her E n d p oi nt(s) ...................................................................................................... 7
3. 4. B aseli ne Varia bles..................................................................................................... 7
3. 5. Safet y E n d p oi nts ....................................................................................................... 7
3. 5. 1. A d verse E ve nts ............................................................................................. 7
3. 5. 2. L a b orat or y Data............................................................................................ 8
3. 5. 3. Vital Si g ns .................................................................................................... 8
3. 5. 4. Electr ocar di o gra ms ....................................................................................... 8
4. A N A L Y SI S S E T S ( P O P U L A T I O N S F O R A N A L Y SI S)..................................................... 9
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S ...................................................... 9
5. 1. H y p ot heses a n d Decisi o n R ules ................................................................................ 9
5. 2. Ge neral Met h o ds ....................................................................................................... 9
5. 3. Met h o ds t o Ma na ge Missi n g Data .......................................................................... 1 0
5. 3. 1. Safet y Data .................................................................................................. 1 0
5. 3. 2. P har mac o ki netic Data .................................................................................1 0
6. A N A L Y S E S A N D S U M M A RI E S ...................................................................................... 1 1
6. 1. Pri mar y  E n d p oi nt(s)................................................................................................ 1 1
6. 2. Sec o n dar y  E n d p oi nt(s)............................................................................................ 1 1
6. 2. 1. Sec o n dar y  P K E n d p oi nts............................................................................ 1 1
6. 3. Ot her E n d p oi nts ....................................................................................................... 1 2
...............................................................................1 2
6. 3. 2. P K C o nce ntrati o n of sis u nat o vir fr o m paire d sa m ples o btai ne d via 
micr osa m pli n g c o m pare d t o ve n o us sa m pli n g................................................. 1 2
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 3 of 1 7
6. 4. S u bset A nal y ses....................................................................................................... 1 2
6. 5. Bas eli ne a n d Ot her S u m maries a n d A nal ys es ......................................................... 1 3
6. 5. 1. Baseli ne S u m maries .................................................................................... 1 3
6. 5. 2. St u d y  C o n d uct a n d Partici pa nt Dis p ositi o n................................................ 1 3
6. 5. 3. St u d y  Treat me nt E x p os ure ......................................................................... 1 3
6. 5. 4. Pri or, C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts ........................ 1 3
6. 6. Safet y S u m maries a n d A nal yses ............................................................................. 1 3
6. 6. 1. A d verse E ve nts ........................................................................................... 1 3
6. 6. 2. L a b orat or y Data.......................................................................................... 1 3
6. 6. 3. Vital Si g ns .................................................................................................. 1 4
6. 6. 4. Ele ctr ocar di o gra ms ..................................................................................... 1 4
7. I N T E RI M A N A L Y S E S ....................................................................................................... 1 4
7. 1. I ntr o d ucti o n ............................................................................................................. 1 4
7. 2. I nteri m A nal ys es a n d S u m maries ............................................................................ 1 4
8. R E F E R E N C E S .................................................................................................................... 1 4
9. A P P E N DI C E S ..................................................................................................................... 1 5
9. 1. A p pe n di x 1: Cate g orical Classes f or E C G a n d Vital Si g ns .................................... 1 5
................................................. 1 6
9. 3. A p pe n di x 3: L ist of A b bre viati o ns.......................................................................... 1 7
LI S T O F T A B L E S
Ta ble 1. S u m mar y  of C ha n ges...................................................................................................4
Ta ble 2. St u d y  O bjecti ves a n d E n d poi nts .................................................................................. 5
Ta ble 3. Sis u nat o vir Plas ma P K Para meter Defi niti o ns ............................................................ 6
Ta ble 4. P K Para meters t o be S u m marize d Descri pti vel y .......................................................1 1
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 4 of 1 7
N O T E: It alicize d te xt wit hi n t his d oc u me nt has bee n ta ke n ver bati m fr o m t he Pr ot oc ol.
1. V E R SI O N HI S T O R Y
T a ble 1 . S u m m ar y of C h a n ges
Versi o n /
D ate
Ass oci ate d 
Pr ot oc ol 
A m e n d me nt
R ati o n ale
S pecific C h a n ges
1
0 8 A u g 2 0 2 3
Ori gi nal 
9 J u n 2 0 2 3
N/ A  
N/ A
2. I N T R O D U C TI O N
P F -0 7 9 2 3 5 6 8 (sis u n at ovir, f or merly R V 5 2 1) is bei n g devel o pe d t o act as a hi g hly p ote nt, 
selective, or ally av ail a ble a ge nt t o tre at R S V i nfecti o n. Sis u n at ovir is a n i n hi bit or of R S V 
f usi o n ( F) pr otei n me di ate d f usi o n t h at is c urre ntly bei n g i nvesti g ate d f or t he tre at me nt of 
R S V i nfecti o n.
T he p ur p ose of t he st u dy is t o ev al u ate t he P K, s afety a n d t oler a bility of sis u n at ovir 
( P F-0 7 9 2 3 5 6 8) i n C hi nese he alt hy a d ult p a rtici p a nts. T his i nf or m ati o n is bei n g c ollecte d t o 
s u p p ort f urt her cli nic al devel o p me nt as well as dr u g re gistr ati o n i n C hi n a.
T his statistical a nal ysis pla n (S A P ) pr o vi des t he detaile d met h o d ol o g y  f or s u m mar y a n d 
statistical a nal yses of t he data c ollecte d i n S t u d y C 5 2 4 1 0 1 8.   
2. 1. M o dific ati o ns
t o t he A n al ysis Pl a n Descri be d i n t he Pr ot oc ol
N o ne.
2. 2. St u d y O bjecti ves , E n d p oi nts, a n d Esti m a n ds
T he f oll o wi n g are t he o bjecti ves a n d e n d p oi nts i n t his st u d y. Esti ma n d fra me w or k will n ot be 
a p plie d t o t his P hase 1 st u d y i n healt h y partici pa nts. 
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 5 of 1 7
T a ble 2 . St u d y O bjecti ves a n d E n d p oi nts
T y pe
O bjectives
E n d p oi nts
Pri m ary: 
Pri m ary:
P har m ac o ki netics 
T o ev al u ate t he P K of sis u n at ovir
after si n gle d ose a n d m ulti ple 
d oses i n C hi nese he alt hy 
p artici p a nts
Sis u n at ovir pl as m a ex p os ure f or si n gle a n d 
m ulti ple d oses: 

P ost d ose o n D ay 1: C m ax , A U Cl ast, A U C t a u
(t a u = 1 2), a n d A U C i nf as d at a per mit.

P ost first d ose o n D ay 4: C m ax , A U Ct a u

P ost d ose o n D ay 8: C m ax , A U Ct a u
Sec o n d ary: 
Sec o n d ary:
P har m ac o ki netics 
T o f urt her c h ar acterize t he P K 
pr ofile of sis u n at ovir after si n gle 
d ose a n d m ulti ple d oses of 
sis u n at ovir i n C hi nese he alt hy 
p artici p a nts
A d diti o n al sis u n at ovir pl as m a P K p ar a meters: 

P ost d ose o n D ay 1: T m ax , t½ , M R T, Vz/ F, a n d 
C L/ F as d at a per mit

P ost first d ose o n D ay 4: T m ax

P ost d ose o n D ay 8: T m ax , t½ , acc u m ul ati o n 
r ati o o n A U Ct a u ( Rac) a n d o n Cm ax ( Rac,C m ax ), 
M R T, V
z/ F, C L/ F, C tr o u g h, C av, A U Cl ast, A U Ci nf
a n d P T R as d at a per mit
Safet y

T o ev al u ate t he s afety a n d 
t oler a bility of sis u n at ovir 
f oll o wi n g si n gle a n d m ulti ple d ose 
i n C hi nese he alt hy p artici p a nts

A Es/ S A Es, cli nic al s afety l a b or at ory tests, 
vit al si g ns, 1 2 -le a d E C Gs
Terti ary/ E x pl or at ory: 
Terti ary/ E x pl or at ory:
P har m ac o ki netics 
T o ex pl ore P K of sis u n at ovir by 
micr os a m pli n g tec h ni q ue, if 
fe asi ble

C o nce ntr ati o n of sis u n at ovir fr o m p aire d 
s a m ples o bt ai ne d vi a micr os a m pli n g 
c o m p are d t o pl as m a s a m pli n g (if p ossi ble)
2. 3. St u d y Desi g n
T his is a P h ase 1, si n gle -ce nter, o pe n -l a bel a n d si n gle -ar m st u dy t o i nvesti g ate P K, s afety 
a n d t oler a bility of 2 0 0 m g sis u n at ovir give n as a si n gle d ose o n D ay 1 i n a f aste d st ate 
f oll o we d by re pe ate d t wice d aily d oses ( 2 0 0 m g BI D, Q 1 2 h o urs) fr o m D ays 4-7 pl us 1 
m or ni n g d ose o n D ay 8 i n a fe d st ate i n C hi nese he alt hy p artici p a nts. A p pr oxi m ately 1 2 
p artici p a nts i n t ot al will be i ncl u de d i n t his st u dy. I f a p artici p a nt disc o nti n ues bef ore 
c o m pleti n g t he st u dy, or wit h dr a ws f or re as o ns u nrel ate d t o t he s afety of t he tre at me nt, t he 
p artici p a nt m ay be re pl ace d at t he discreti o n of t he i nvesti g at or u p o n c o ns ult ati o n wit h t he 
s p o ns or.
T he st u dy will c o nsist of a Scree ni n g visit, a Tre at me nt peri o d of si n gle d osi n g ( D ay -1 t o 
D ay 3) a n d m ulti ple d osi n g ( D ay 4 t o D ay 1 1), a n d a F oll o w- u p c o nt act. T he t ot al d u r ati o n 
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 6 of 1 7
of p artici p ati o n fr o m t he Scree ni n g visit t o t he F oll o w- u p c o nt act will be u p t o a p pr oxi m ately 
7 1 d ays.
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S: D E FI NI TI O N S A N D 
C O N V E N TI O N S
3. 1. Pri m ar y E n d p oi nt(s)
As liste d i n Secti o n 2. 2 , t he pri mar y e n d p oi nts are relate d t o Sis u nat o vir plas ma e x p os ure 
after si n gle a n d m ulti ple d oses, a n d are detaile d i n Ta ble 3.
3. 2. Sec o n d ar y E n d p oi nt(s)
T he sec o n dar y  e n d p oi nts are a d diti o nal p har mac o ki netics para meters after si n gle a n d 
m ulti ple d oses of Sis u nat o vir as detaile d i n Ta ble 3 , as well as safety e n d p oi nts descri be d i n 
Secti o n 3. 5 .
T a ble 3. Sis u n at o vir Pl as m a P K P ar a meter Defi niti o ns
P ar a meter
St u dy 
D ay 
Defi niti o n
Met h o d of Deter mi n ati o n
C m ax
1 , 4, 8
M axi m u m o bserve d c o nce ntr ati o n
O bserve d directly fr o m d at a
T m ax
1 , 4, 8
Ti me t o re ac h m axi m u m 
c o nce ntr ati o n
O bserve d directly fr o m d at a
A U C i nfa
1 , 8
Are a u n der t he c o nce ntr ati o n -ti me 
c urve fr o m ti me 0 t o i nfi nity
A U C l ast + ( C l ast/kel),
w here C l ast is t he pre dicte d pl as m a
c o nce ntr ati o n at t he l ast q u a ntifi a ble ti me 
p oi nt esti m ate d fr o m t he l o g -li ne ar 
re gressi o n a n alysis
A U C l ast
1 , 8
Are a u n der t he c o nce ntr ati o n -ti me 
c urve fr o m ti me 0 t o t he ti me of 
l ast q u a ntifi a ble c o nce ntr ati o n
Li ne ar/ L o g tr a pez oi d al met h o d
A U C t a u
1 , 4, 8
Are a u n der t he c o nce ntr ati o n ti me 
c urve fr o m ti me 0 t o t he ti me of t he 
e n d of t he d osi n g i nterv al (t a u), 
w here t a u = 1 2 h o urs
Li ne ar/ L o g tr a pez oi d al met h o d.
t½ a
1 , 8
Ter mi n al h alf -life
L o g e( 2)/kel, w here kel is t he ter mi n al
p h ase r ate c o nst a nt c alc ul ate d by a li ne ar 
re gressi o n of t he l o g-li ne ar
c o nce ntr ati o n -ti me c urve
M R T
a
1 , 8
Me a n resi de nce ti me
D ay 1 : M R T = A U M C
i nf/ A U Ci nf
D ay 8 : [ A U M Ct a u + t a u( A U C i nf-
A U C t a u)]/ A U Ct a u
w here A U M C i nf is the are a u n der t he first 
m o me nt c urve fr o m zer o ti me t o i nfi nity
A U M C t a u is are a u n der t he first m o me nt 
c urve over t he d osi n g i nterv al t a u .
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 7 of 1 7
T a ble 3. Sis u n at o vir Pl as m a P K P ar a meter Defi niti o ns
P ar a meter
St u dy 
D ay 
Defi niti o n
Met h o d of Deter mi n ati o n
V z/ Fa
1
A p p are nt v ol u me of distri b uti o n
D ose/( A U C i nf × k el)
C L/ F a
1 , 8 
A p p are nt or al cle ar a nce
D ose/ A U C i nf
R ac a
8
Acc u m ul ati o n r ati o o n A U C t a u
A U C 1 2 (D ay 8 ) / A U C1 2 (D ay 4 )
R ac, C m ax a
8
Acc u m ul ati o n r ati o o n C m ax
C m ax (D ay 8 ) /C m ax (D ay 4 )
C tr o u g h
6, 7, 8
L o west c o nce ntr ati o n o bserve d 
d uri n g t he d osi n g i nterv al 
O bserve d directly fr o m d at a
C av
8
Aver a ge c o nce ntr ati o n at ste a dy 
st ate 
A U C 1 2 ( D ay 8) / 1 2 h o urs.
V z/ Fa
8
A p p are nt v ol u me of distri b uti o n at 
ste a dy st ate 
V z/ F = D ose/( A U Ct a u × k el)
P T R
8 
P e ak-tr o u g h r ati o
C m ax / Ctr o u g h
a.
If data per mit.
3. 3. Ot her E n d p oi nt (s)
T he f oll o wi n g e xpl orat or y e n d p oi nts are defi ne d i n t his st u d y :


C o nce ntr ati o n of sis u n at ovir fr o m p aire d s a m ples o bt ai ne d vi a micr os a m pli n g
c o m p are d t o pl as m a s a m pli n g (if p ossi ble) .
3. 4. B aseli ne V ari a bles
T here are n o baseli ne varia bles t o be use d as c o variates or stratificati o n fact ors i n t his st u d y .
Baseli ne c haracteristics will be c ollecte d acc or di n g t o t he sc he d ule of acti vities ( S o A) as 
s pecifie d i n t he pr ot oc ol.
3. 5. S afet y E n d p oi nts
T he f oll o wi n g data will be c o nsi dere d i n sta n dar d safet y s u m maries (see pr ot oc ol f or 
c ollecti o n da ys, assess me nt pr oce d ures , a n d list of para meters):

A d verse e ve nts ( A E) / Seri o us a d verse e ve nts ( S A E)

La b orat or y  tests data

Vital si g ns data

1 2- lea d E C G res ults
3. 5. 1. A d verse E ve nts
A n y  a d verse e ve nts occ urri n g f oll o wi n g start of treat me nt will be c o nsi dere d as treat me nt 
e mer ge nt a d verse e ve nt ( T E A E). If a n A E starts o n t he sa me da y  as t he first d ose date, it will 
be c o nsi dere d treat me nt e mer ge nt u nless t he C R F data i n dicates ot her wise via e x plicitl y  
rec or di n g ti me f or A E o nset w hic h was occ urre d bef ore t he first treat me nt d osi n g. E ve nts 
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 8 of 1 7
t hat occ ur d uri n g f oll o w- u p wit hi n t he la g ti me of u p t o 2 8-3 5 da y s after t he last d ose of 
st u d y i nter ve nti o n will be c o u nte d as treat me nt e mer ge nt a n d attri b ute d t o t he last treat me nt 
ta ke n. E ve nts t hat occ ur d uri n g t he was h o ut peri o d bet wee n st u dy peri o ds will be c o u nte d as
treat me nt e mer ge nt a n d attri b ute d t o t he pre vi o us treat me nt ta ke n. T he ti me peri o d f or 
c ollecti n g A Es (“acti ve c ollecti o n peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he 
partici pa nt pr o vi des i nf or me d c o nse nt. T he al g orit h m will n ot c o nsi der a n y e ve nts t hat starte d 
pri or t o t he first d ose date.
3. 5. 2. L a b or at or y D at a
Safe t y la b orat or y tests will be perf or me d as descri be d i n t he pr ot oc ol. 
T o deter mi ne if t here are a n y cli nicall y si g nifica nt la b orat or y a b n or malities, t he hae mat ol o gical, 
cli nical c he mistr y a n d uri nal ysis safet y tests will be assesse d a gai nst t he criteria s pe cifie d i n t he 
s p o ns or re p orti n g sta n dar ds.T he baseli ne meas ure me nt is t he val ue c ollecte d o n Da y  - 1 pri or t o 
t he treat me nt start, or t he last pre -d ose meas ure me nt c ollecte d if t he Da y  -1 meas ure me nt is n ot 
a vaila ble.
3. 5. 3. Vit al Si g ns 
S u pi ne bl o o d press ure ( B P), p ulse rate ( P R) a n d te m perat ure will be meas ure d at ti mes s pecifie d 
i n t he S o A gi ve n i n t he pr ot oc ol. 
T he baseli ne meas ure me nt is t he pre d ose meas ure me nt o n Da y 1 or t he last pre d ose meas ure me nt
c ollecte d if t he Da y 1 meas ure me nt is n ot a vaila ble . 
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y first s u btracti n g t he baseli ne val ue 
fr o m eac h p ost-d ose meas ure me nt t o gi ve t he c ha n ge fr o m baseli ne. T he ma xi m u m of t hese 
val ues will t he n be selecte d, e xce pt i n t he case w here a partici pa nt d oes n ot s h o w a n i ncrease. I n 
s uc h a n i nsta nce, t he mi ni m u m decrease s h o ul d be ta ke n. 
Si milarl y , t he ma xi m u m decrease fr o m baseli ne will be deter mi ne d b y selecti n g t he mi ni m u m 
val ue of t he c ha n ges fr o m baseli ne. I n cases w here a partici pa nt d oes n ot s h o w a decr ease, t he 
mi ni m u m i ncrease s h o ul d be ta ke n. 
3. 5. 4. Electr oc ar di o gr a ms 
A 1 2 -lea d E C G will be o btai ne d at s pecifie d da y a n d ti me p oi nt as i n dicate d i n t he S o A of t he 
pr ot oc ol . If n ot s u p plie d, Q Tc F will be deri ve d usi n g Fri dericia’s heart rate c orrecti o n f or m ula: 
Q Tc F = Q T / ( R R) ^( 1/ 3) w here R R = 6 0/ H R (if n ot pr o vi de d) 
T he baseli ne val ue is t he pre d ose meas ure me nt o n Da y 1 or t he last pre d ose meas ure me nt 
c ollecte d if t he Da y 1 meas ure me nt is n ot a vaila ble . 
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y first s u btracti n g t he baseli ne val ue 
fr o m eac h p ost d ose meas ure me nt t o gi ve t he c ha n ge fr o m baseli ne. T he ma xi m u m of t hese 
val ues o ver t he res pecti ve peri o d will t he n be selecte d, e xce pt i n t he case w here a partici pa nt 
d oes n ot s h o w a n i ncrease. I n s uc h a n i nsta nce, t he mi ni m u m decrease s h o ul d be ta ke n.
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 9 of 1 7
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S )
D ata f or all partici pa nts will be assesse d t o deter mi ne if partici pa nts meet t he criteria f or 
i ncl usi o n i n eac h a nalys is p o p ulati o n pri or t o u n bli n di n g a n d releasin g t he data base a n d 
classificati o ns will be d oc u me nte d per sta n dar d o perati n g pr oce d ures.
T he f oll o wi n g a nal ys is set are defi ne d i n t his st u d y:
P artici p a nt A n alysis Set
Descri pti o n
E nr olle d 
“ E nr olle d ” me a ns a p artici p a nt’s, or t heir le g ally a ut h orize d 
re prese nt ative’s, a gree me nt t o p artici p ate i n a cli nic al st u dy 
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
assi g n me nt t o st u dy i nterve nti o n.
P K C o nce ntr ati o n 
A n alysis Set
T he P K c o nce ntr ati o n a n alysis set is defi ne d as all p artici p a nts 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n a n d i n w h o m at 
le ast 1 pl as m a c o nce ntr ati o n v al ue is re p orte d.
P K P ar a meter A n alysis 
Set
T he P K p ar a meter a n alysis set is defi ne d as all p artici p a nts 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n a n d h ave at le ast 
1 of t he P K p ar a meters of i nterest c alc ul ate d.
S afety a n alysis set
All p artici p a nts w h o t ake at le ast 1 d ose of st u dy i nterve nti o n. 
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S
Fi nal a nal y sis will be perfor me d after st u d y partici pa nt data set release f oll o wi n g t he last 
partici pa nt last visit.
5. 1. H y p ot heses a n d Decisi o n R ules
N o sta tistical h yp ot hesis will be teste d i n t his st u d y.
5. 2. Ge ner al Met h o ds
Descri pti ve a nal yses will be perf or me d. S o me meas ures will be s u m marize d usi n g gra p hical 
re prese ntati o ns. 
S u m maries b y  treat me nt will i ncl u de s u m maries b y a d mi nistrate d d ose a n d fe d/faste d c o n diti o n, 
w he n a p plica ble.   
F or bi nar y  or cate g orical varia bles, n u m ber of partici pa nts, n u m bers a n d perce nta ges of 
partici pa nts meeti n g t he cate g orical criteria will be prese nte d i n acc or da nce wit h t he s p o ns or 
re p orti n g sta n dar ds.
F or c o nti n u o us varia bles, t he data will be s u m marize d usi n g t he n u m ber of partici pa nts, mea n, 
me dia n, sta n dar d de viati o n ( S D), mi ni m u m, a n d ma xi m u m i n acc or da nce wit h t he s p o ns or 
re p orti n g sta n dar ds. F or a p pr o priate P K para meters, ge o metric mea n a n d ge o metric c oefficie nt of 
variati o n ( % C V) will als o be s u m marize d. 
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 0 of 1 7
5. 3.
Met h o ds t o M a n a ge Missi n g D at a
5. 3. 1. S afet y D at a
F or t he a nal ys is of safet y e n d p oi nts, t he s p o ns or data sta n dar d r ules f or i m p utati o n will be
a p plie d.
5. 3. 2. P h ar m ac o ki netic D at a
C o nce ntr ati o ns Bel o w t he Li mit of Q u a ntific ati o n 
I n all data prese ntati o ns (e xce pt listi n gs), c o nce ntrati o ns bel o w t he li mit of q ua ntificati o n ( B L Q) 
will be set t o zer o. I n listi n gs B L Q val ues will be re p orte d as “ < L L Q”, w here L L Q will be 
re place d wit h t he val ue f or t he l o wer li mit of q ua ntificati o n. 
De vi ati o ns, Missi n g C o nce ntr ati o ns a n d A n o m al o us V al ues
I n s u m mar y ta bles a n d pl ots of mea n/ me dia n pr ofiles, statistics will be calc ulate d ha vi n g set 
c o nce ntrati o ns t o missi n g if o ne of t he f oll o wi n g cases is tr ue: 
1. A c o nce ntrati o n has bee n c ollecte d as N D (ie, n ot d o ne) or N S (ie, n o sa m ple). 
2. A de viati o n i n sa m pli n g ti me is of s ufficie nt c o ncer n or a c o nce ntrati o n has bee n fla g ge d as 
a n o mal o us b y t he p har mac o ki neticist.
N ote t hat s u m mar y  statistics will n ot be prese nte d at a partic ular ti me p oi nt if m ore t ha n 5 0 % of 
t he data are missi n g. 
A n a n o mal o us c o nce ntrati o n val ue is o ne t hat, after verificati o n of bi oa nal ytical vali dit y, is 
gr ossl y i nc o nsiste nt wit h ot her c o nce ntrati o n data fr o m t he sa me i n di vi d ual or fr o m ot her 
partici pa nts. F or e xa m ple, a B L Q c o nce ntrati o n t hat is bet wee n q ua ntifi a ble val ues fr o m t he sa me 
d ose is c o nsi dere d as a n o mal o us. A n o mal o us c o nce ntrati o n val ues ma y be e xcl u de d fr o m P K 
a nal ysis at t he discreti o n of t he P K a nal yst or p har mac o ki neticist.
P K P ar a meters 
Act ual P K sa m pli n g ti mes will be use d i n t he deri vati o n of P K para meters. 
If a P K para meter ca n n ot be deri ve d fr o m a partici pa nt’s c o nce ntrati o n data, t he para meter will 
be c o de d as N C (ie, n ot calc ulate d). ( N ote t hat N C val ues will n ot be ge nerate d be y o n d t he da y 
t hat a partici pa nt disc o nti n ues). 
I n s u m mar y ta bles, statistics will be calc ulate d b y setti n g N C val ues t o missi n g; a n d statistics will 
be prese nte d f or a partic ular treat me nt wit h ≥3 e val ua ble meas ure me nts. P K para meter a nal yses 
will n ot be perf or me d f or a partic ular para meter if m ore t ha n 5 0 % of t he d ata are N C. 
If a n i n di vi d ual partici pa nt has a k n o w n biase d esti mate of a P K para meter (e. g. d ue t o a n 
u ne x pecte d e ve nt s uc h as v o miti n g bef ore all t he c o m p o u n d is a de q uatel y a bs or be d fr o m t he 
gastr oi ntesti nal tract), t his will be f o ot n ote d i n s u m mar y ta b les a n d will n ot be i ncl u de d i n t he 
calc ulati o n of s u m mar y statistics or statistical a nal yses.
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 1 of 1 7
6. A N A L Y S E S A N D S U M M A RI E S
6. 1. Pri m ar y E n d p oi nt (s)
T he P K para meters detaile d i n Secti o n 3. 1 will be liste d a n d descri pti vel y s u m marize d f or 
partici pa nts i n t he P K para meter a nalys is set (as defi ne d i n Secti o n 4 ). Missi n g val ues will be 
ha n dle d as detaile d i n Secti o n 5. 3. 2 . The P K para meters will be s u m marize d b y  st u d y d a y. 
Eac h s u m mar y will i ncl u de t he set of s u m mar y statistics as s pecifie d i n Ta ble 4 . 
T a ble 4 . P K P ar a meters t o be S u m m arize d Descri pti vel y
P ar a meter
S u m m ar y St atistics
C ma x , A U C last, AU C ta u,
A U C i nf, M R T,
V z/ F, C L / F, Rac, 
R ac, C ma x, C tr o u g h, C a v, P T R
N, arit h metic mea n, me dia n, c v %, S D , mi ni m u m,
ma xi m u m, ge o metric mea n a n d ge o metric c v %.
T ma x
N, me dia n, mi ni m u m, ma xi m u m.
t½
N, arit h metic mea n, me dia n, S D ,
mi ni m u m, ma xi m u m.
F or A U C last, AU C ta u, AU C i nf, a n d C ma x , b o x a n d w his ker pl ots f or i n di vi d ual partici pa nt 
para meters o verlai d wit h ge o metric mea ns will be pl otte d b y  d a y  a n d be prese nte d i n t he 
sa me fi g ure. f or eac h a nal yte. 
6. 2. Sec o n d ar y E n d p oi nt(s)
6. 2. 1. Sec o n d ar y P K E n d p oi nts
A nal y ses si milar t o t h ose pla n ne d f or t he pri mar y P K e n d p oi nts will be use d f or t he 
sec o n dar y P K e n d p oi nts usi n g t he s u m mar y  statistics as s pecifie d i n Ta ble 4 . T he s u m maries 
will be pr ese nte d b y st u d y da y.
P K c o nce ntr ati o n s u m m aries:
Prese ntati o n f or t he plas ma c o nce ntrati o ns of sis u nat o vir will be ge nerate d usi n g t he P K 
c o nce ntrati o n a nal ys is set (as defi ne d i n Secti o n 4 ) i ncl u di n g:

a listi n g of all c o nce ntrati o ns s orte d b y  partici pa nt I D, st u d y d a y a n d n o mi nal ti me p ost -
d ose. T he c o nce ntrati o n listi n g will als o i ncl u de t he act ual ti mes. De viati o ns fr o m t he 
n o mi nal ti me will be gi ve n i n a se parate listi n g.

a s u m mar y of c o nce ntrati o ns b y  st u d y da y a n d n o mi nal ti me p ost -d ose, w here t he set of
statistics will i ncl u de n, mea n, me dia n, S D, c v %, mi ni m u m, ma xi m u m a n d t he n u m ber of 
c o nce ntrati o ns t hat are ab o ve or e q ual t o t he L L Q.

me dia n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal
ti me p ost-d ose b y  st u d y da y i n t he sa me fi g ure. 
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 2 of 1 7

mea n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal ti me
p ost -d ose b y  st u d y da y i n t he sa me fi g ure.

i n di vi d ual c o nce ntrati o n-ti me pl ots  ( o n b ot h li near a n d se mi-l o g scales) a gai nst act ual 
ti me p ost- d ose f or all s u bjects i n t he sa me fi g ure (t here will be se parate s pa g hetti pl ots 
pa ge d b y st u d y da y per scale).
6. 3. Ot her E n d p oi nt s
 
 
 
 
 
6. 3. 2. P K C o nce ntr ati o n of sis u n at o vir fr o m p aire d s a m ples o bt ai ne d vi a 
micr os a m pli n g c o m p are d t o ve n o us s a m pli n g
C ma x a n d A U C ta u deri ve d fr o m bl o o d sa m ples c ollecte d usi n g t he Tass o ® M 2 0 de vice 
a dj uste d f or B/ P rati o will be s u m marize d f or sis u nat o vir a n d will i nl uc de t he set of s u m mar y 
statistics as sep ecifie d i n Ta ble 4 . S u m mar y  statistics ( N, ge o metric mea n, ge o metric C V, 
me dia n, arit h metic mea n, C V, mi ni m u m, ma xi m u m) of t he w h ole bl o o d c o nce ntrati o ns, 
plas ma e q ui vale nt c o nce ntrati o ns b y  micr osa m pli n g usi n g i n di vi d ual B/ P rati o a n d plas ma 
e q ui vale nt c o nce ntrati o n b y  micr osa m pli n g usi n g p o p ulati o n ge o metric mea n B/ P rati o at 
n o mi nal ti me of c ollecti o n as defi ne d i n S o A of t he pr ot oc ol f or eac h treat me nt ar m will be 
calc ulate d.
F urt her m ore, t o deter mi ne c orrelati o n i n c o nce ntrati o ns deri ve d fr o m ti me matc he d Tass o ® 
M 2 0 micr o sa m pli n g (calc ulate d usi n g i n di vi d ual or p o p ulati o n) a n d tra diti o nal ve n o us 
plas ma sa m pli n g, Bla n d -Alt ma n pl ot a nal y sis will be perf or me d t o e val uate t he bias a n d S D 
of t he bias bet wee n t he mea n differe nces a n d t o esti mate a n a gree me nt i nter val wit hi n a 9 5 % 
c o nfi de nce li mit. Pl ots of t he differe nce bet wee n t he t w o sa m ples ( o n Y -a xis) as a f u ncti o n of 
t he a vera ge of t he t w o sa m ples ( o n X-a xis). T hese pl ots will be c ol ore d b y  partici pa nt i n 
a d diti o n t o b y ti me p oi nt.  In a d diti o n, a c orrelati o n pl ot of t he pla s ma P K sa m ple ( o n X-a xis) 
a n d Tass o P K sa m ple ( o n Y- a xis) will be create d i ncl u di n g a li ne of e q ualit y  Y = X. 
T he se res ults will be re p orte d i n a se parate Cli nical Bi oa nal yt ics s u m mar y re p ort a n d ma y 
n ot be i ncl u de d i n t he C S R .
6. 4. S u bset A n al yses
N o s u bset a nal ys es will be perf or me d.
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 3 of 1 7
6. 5. B aseli ne a n d Ot her S u m m aries a n d A n al yses
6. 5. 1. B aseli ne S u m m aries
D e m o grap hic a n d baseli ne c haracteristics c ollecte d pri or t o t he first d osi n g will be 
s u m marize d f oll o wi n g t he s p o ns or re p orti n g sta n dar d. B M I will be deri ve d usi n g t he 
f oll o wi n g f or m ula:   =    ℎ (  )/ [ ℎ  ℎ( )]  .
6. 5. 2. St u d y C o n d uct a n d P artici p a nt Dis p ositi o n
A s u m mar y f or partici pa nt dis p ositi o n will be ge nerate d b y  peri o d. Fre q ue nc y c o u nts a n d 
perce nta ges will be s u p plie d f or partici pa nt disc o nti n uati o n(s). Data will be re p orte d i n 
acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds.
6. 5. 3. St u d y Tre at me nt E x p os ure
St u d y  treat me nt e x p os ure will be liste d.
6. 5. 4. Pri or, C o nc o mit a nt Me dic ati o ns a n d N o n d r u g T re at me nts
All pri or, c o nc o mita nt me dicati o n(s) as well as n o n- dr u g trea t me nt(s) will be re p orte d
acc or di n g t o c urre nt s p o ns or re p orti n g sta n dar ds.
6. 6. S afet y S u m m aries a n d A n al yses
All safet y  a nal yses will be perf or me d o n t he Safet y A nal ysis Set. 
Safet y  data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d descri pti vel y , 
w here a p pr o priate.
Me dical hist or y  a n d p h ysical e xa mi nati o n c ollecte d d uri n g t he c o urse of t he st u d y, will be 
c o nsi dere d s o urce data a n d will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. 
H o we ver, a n y u nt o war d fi n di n gs i de ntifie d o n p h ysical e xa mi nati o ns c o n d ucte d d uri n g t he 
acti ve c ollecti o n peri o d will be ca pt ure d as A Es, if t h ose fi n di n gs meet t he defi niti o n of a n 
A E. Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as 
la b orat or y data, E C Gs, a n d vital si g ns, will be c o nsi dere d s o urce data, a n d will n ot be 
re q uire d t o be re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will 
be re p orte d.
6. 6. 1. A d verse E ve nts
A d verse e ve nts will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g st a n dar ds. All A Es will 
be liste d. T E A Es will be prese nte d wit h hi g h -le vel s u m ma y, s u m mar y b y Sys te m O r ga n C lass
( S O C) a n d Preferre d T er m ( P T). 
6. 6. 2. L a b or at or y D at a
La b orat or y  data will be liste d a n d s u m marize d i n acc or da nce wit h t he s p o ns or re p orti n g 
sta n dar ds. La b orat or y  test a b n or malit y will be s u m marize d ( wit h or wit h o ut re gar d t o 
baseli ne a b n or malit y ). Baseli ne is as defi ne d i n Secti o n 3. 5. 2 .
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 4 of 1 7
6. 6. 3. Vit al Si g ns
A bs ol ute val ues a n d c ha n ges fr o m baseli ne i n bl o o d press ure, p ulse rate, a n d te m perat ure 
will be liste d a n d s u m marize d b y st u d y da y a n d ti me p ost -d ose , acc or di n g t o s p o ns or 
re p orti n g sta n dar ds. Baseli ne is as defi ne d i n Secti o n 3. 5. 3 .
N u m bers a n d perce nta ges of partici pa nts meeti n g t he cate g orical criteria as defi ne d i n 
Secti o n 9. 1 A p pe n di x 1 will be s u m marize d. All pla n ne d a n d u n pla n ne d p ost - d ose ti me 
p oi nts will be c o u nte d i n t he cate g orical s u m mar y.
6. 6. 4. Electr oc ar di o gr a m s
A bs ol ute val ues a n d c ha n ges fr o m baseli ne i n Q T i nter val, heart rate, Q Tc F, Q Tc B, P R i nter val 
a n d Q R S will be s u m marize d st u d y a n d ti me p ost -d ose usi n g s p o ns or re p orti n g sta n dar ds. Ta bles 
will be pa ge d b y para meter. Baseli ne is as defi ne d i n Secti o n 3. 5. 4 .
Cate g orical s u m maries f or Q Tc F, P R i nter val, a n d Q R S meeti n g t he criteria as defi ne d i n 
Secti o n 9. 1 A p pe n di x 1 will be s u m marize d. A ll pla n ne d a n d u n pla n ne d p ost- d ose ti me p oi nts 
will be c o u nte d i n t he cate g orical s u m mar y .
Listi n gs of partici pa nts wit h a n y si n gle p ost - d ose val ue > 5 0 0 msec will als o be pr o d uce d f or
Q Tc F.
7. I N T E RI M A N A L Y S E S
7. 1. I ntr o d ucti o n
T here will be n o i nteri m a nal ys is i n t his st u d y.
7. 2. I nteri m A n al yses a n d S u m m aries
N o ne.
8. R E F E R E N C E S
N o ne.
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 5 of 1 7
9. A P P E N DI C E S
9. 1. A p pe n di x 1: C ate g oric al Cl asses f or E C G a n d Vit al Si g ns 
C ate g ories f or Q Tc F
Ma xi m u m a bs ol ute val ue of Q Tc F ( msec)
> 4 5 0 a n d ≤4 8 0
> 4 8 0 a n d ≤5 0 0
> 5 0 0
Ma xi m u m i ncrease fr o m baseli ne i n Q Tc F 
( msec)
> 3 0 a n d ≤6 0
> 6 0
C ate g ories f or P R i nter v al a n d Q R S
P R i nter val ( ms) 
ma x. ≥3 0 0
P R ( ms) i ncrease fr o m 
baseli ne
b aseli ne > 2 0 0 a n d 
ma x. i ncrease ≥2 5 % 
b aseli ne ≤2 0 0 a n d
ma x. i ncrease ≥5 0 %
Q R S ( ms) 
ma x. ≥1 4 0
Q R S ( ms) i ncrease fr o m
baseli ne
ma x. i ncrease ≥5 0 % 
C ate g ories f or Vit al Si g ns
S y st olic B P ( m m H g)
mi n. < 9 0
S y st olic B P ( m m H g) c ha n ge fr o m baseli ne
ma x. decrease ≥3 0
ma x. i ncrease ≥3 0
Diast olic B P ( m m H g)
mi n. < 5 0
Diast olic B P ( m m H g) c ha n ge fr o m baseli ne
ma x. decrease ≥2 0
ma x. i ncrease ≥2 0
P ulse rate ( b p m)
mi n. < 4 0
ma x. > 1 2 0
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 6 of 1 7
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)
C CI


Pr ot oc ol C 5 2 4 1 0 1 8 (P F -0 7 9 2 3 5 6 8 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 7 of 1 7
9. 3. A p pe n di x 3: List o f A b bre vi ati o ns
A b bre vi ati o n
Ter m
A E
a d verse e ve nt
A U C
area u n der t he c ur ve
B L Q
bel o w t he li mit of q ua ntitati o n
B P
bl o o d press ure
C av
a vera ge c o nce ntrati o n
CI
c o nfi de nce i nter val
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C L / F
a p pare nt cleara nce
C R F
case re p ort f or m
C tr o u g h
pre -d ose c o nce ntrati o n
C V
c oefficie nt of variati o n
E C G
electr ocar di o gra m
L L Q
l o wer li mit of q ua ntitati o n
M R T
m ea n resi de nce ti me
N C
n ot calc ulate d
N D
n ot d o ne
N S
N o sa m ple
P K
p har mac o ki netic(s)
P R
P ulse rate
P T
preferre d ter m
P T R
pea k -tr o u g h rati o
Q Tc
c orrecte d Q T
Q Tc F
c orrecte d Q T ( Fri dericia met h o d)
R ac
acc u m ulati o n rati o f or A U C ta u
R ac, C ma x
acc u m ulati o n rati o f or C ma x
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S D
sta n dar d de viati o n
S o A
sc he d ule of acti vities
S O C
S y ste m or ga n class
T E A E
Treat me nt -e mer ge nt a d ver e ve nt
V z/ F
a p pare nt v ol u me of distri b uti o n
0 9 0 1 7 7 e 1 9 e 3f 5 9 7 7\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 3 0 0: 4 9 ( G M T)