Clinical trial NCT04909853
Conditions: Renal Impairment
Keywords: SARS-CoV-2 COVID-19
Sponsor: Pfizer
Start date: 2021-06-15; Completion date: 2021-10-07
Enrollment: 35 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of PF-07321332 in combination with the PK boosting agent ritonavir. Participants will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: will be conducted in approximately 24 participants (approximately 8 per group) with stable mild or moderate renal impairment and a control group of participants with normal renal function. Part 2 will be conducted in approximately 8 participants with stable severe renal impairment.

Detailed description:

Arms: arm 1: PF 07321332/ritonavir
Interventions: intervention 1: PF-07321332/ritonavir
Intervention descriptions: intervention 1: PF-07321332 in combination with the PK boosting agent, ritonavir, being developed for the treatment of COVID-19

Protocol documents:
Prot_000.pdf: 
PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE 
PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-07321332
BOOSTED WITH RITONAVIR IN ADULT PARTICIPANTS WITH RENAL 
IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL RENAL 
FUNCTION
Study Intervention Number:
PF-07321332
Study Intervention Name:
N/A
US IND Number:
153517
EudraCT Number:
N/A
ClinicalTrials.gov ID:
NCT04909853
Protocol Number:
C4671011
Phase:
1
Brief Title: Renal Impairment Study of PF-07321332
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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Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Amendment 2
08 July 2021
Amendment 1
25 June 2021
Original protocol
07 May 2021
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any global protocol administrative 
clarification letter.
Protocol Amendment Summary of Changes Table
Amendment 2 (08-July-2021)
Overall Rationale for the Amendment: This study is being amended to reflect the changes 
made to the exclusion criteria in response to the FDA feedback. 
Section # and 
Name
Description of Change
Brief Rationale
Section 5.2.1. All 
Participants
Added the following bullets to 
“Medical Conditions”
1. Positive test result for SARS-
CoV-2 infection at the time of 
screening or Day -1.
2. History of HIV infection, 
hepatitis B, or hepatitis C; positive 
testing at screening for HIV, 
HBsAg, HBcAb, or HCVAb. As an 
exception a positive HBsAb test due 
to Hepatitis B vaccination is 
allowed.
Updated in response to the 
FDA feedback on exclusion 
criteria.
Amendment 1 (25-June-2021)
Overall Rationale for the Amendment: This study is being amended to reflect the changes 
to the study design that number of participants to be enrolled was increased from “32” to 
“36”. Additionally, classification was provided to specify the time for safety follow-up and 
laboratory testing, and eGFR ranges for mild renal impairment. The tables for prohibited and 
precautionary medications in Appendix 8 were updated to provide supplementary details.


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Section # and 
Name
Description of Change
Brief Rationale
Section 1.1 
Synopsis 
Added “Day 1” for safety 
assessment; specified 28 to 35 days 
post “last” dose for safety follow-up 
call; updated the number of 
participants to be enrolled from “32” 
to “36”.
Updates to reflect the changes 
added to the main text.  
Section 1.3 SoA
Specified in footnote “c” that 
telephone contact will occur 28 to 
35 days from “the last 
administration of ritonavir” or from 
the time of early 
termination/discontinuation;
Modified footnote “h” to state tests 
will be performed “at Screening, 
Day -1, Day 3, and early termination 
day”;
Added the following text to footnote 
“j”: “Serum creatinine laboratory 
test may be repeated once to confirm 
results at the discretion of the 
investigator; the last value will be 
used to calculate eGFR.”
Specified time points for COVID-19 
PR-PCR test on “S1, S2, and Day -1 
(only 1 test needed if S2 = Day -1)”.
Classification of time window 
for phone call and specified 
lab tests. 
Section 1.3 SoA, 
Pharmacokinetic 
Sampling Schema
Pharmacokinetic Sampling Schema 
Table was updated to clarify the PK 
sampling schema.
Updated for consistency in 
protocol and in alignment 
with PACL 18 May 2021.
Section 4.1 
Overall design  
In Table 1, for Cohort 2 the 
estimated eGFR range was updated 
to “60 - <90”; for Cohort 3, the 
number of participants was updated 
to “8 (up to 12)”. The number of 
participants was updated 
accordingly to “36” in the following 
text. 
Added “Serum creatinine laboratory 
test may be repeated once to confirm 
results at the discretion of the 
Updates made to reflect the 
current design of the study.
To align with SoA footnote j


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PFIZER CONFIDENTIAL
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Section # and 
Name
Description of Change
Brief Rationale
investigator; the last value will be 
used to calculate eGFR”.
Section 5.1.3. 
Additional 
Inclusion Criteria 
for Participants 
with Impaired 
Renal Function 
(Cohort 1 and 
Cohort 2 & Cohort 
4 [If Applicable] 
Only)
Modified the eGFR range for mild 
renal impairment to “60 –
<90 mL/min”
Updates made to reflect the 
current design of the study.
Section 5.2.1 All 
Participants
Added “at investigator discretion” 
for item 2; 
Updated exclusion time window for 
Covid-19 vaccination to “within the 
past 1 week of dosing, or are to be 
vaccinated with these vaccines at 
any time during  confinement”.
Updates made to reflect the 
current design of the study.
Section 5.3.1 
Meals and Dietary 
Restrictions
Updated study intervention to 
“PF-07321332”.
Added “There are no water 
restrictions for dosing with 
ritonavir.”
Classification for water and 
dietary restrictions. 
Section 10.8 
Appendix 8: 
Prohibited and 
Precautionary 
Concomitant 
Medications That 
May Result in DDI
In Table “Prohibited Medications”: 
added drug class: Anti-gout, 
Antipsychotics.
In Table “Precautionary 
Medications”: added drug class: 
Anesthetic, Antiarrhythmics, 
Anticancer Agents, Antiemetic, 
Antimycobacterial, Antiparasitic
Antipsychotic, Beta Blockers, 
Bronchodilator, Endothelin Receptor 
Antagonist, HIV-1 CCR5 
antagonist, Integrase Inhibitor, 
PDE-5 Inhibitors
Sedative/Hypnotic, Steroids, 
Stimulant.
Provides details on prohibited 
and precautionary 
medications due to potential 
DDI.


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Section # and 
Name
Description of Change
Brief Rationale
Section 11 
Reference
Added reference to investigator’s 
brochure, and ritonavir USPI.
Provides supportive 
information.
Minor editorial changes throughout


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................11
1. PROTOCOL SUMMARY...................................................................................................12
1.1. Synopsis ..................................................................................................................12
1.2. Schema ....................................................................................................................14
1.3. Schedule of Activities .............................................................................................15
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 ......................................................................................19
2.2.4. Clinical Overview.......................................................................................20
2.3. Benefit/Risk Assessment.........................................................................................21
2.3.1. Risk Assessment.........................................................................................22
2.3.2. Benefit Assessment.....................................................................................24
2.3.3. Overall Benefit/Risk Conclusion................................................................24
3. OBJECTIVES AND ENDPOINTS.....................................................................................24
4. STUDY DESIGN.................................................................................................................24
4.1. Overall Design.........................................................................................................24
4.2. Scientific Rationale for Study Design.....................................................................29
4.2.1. Choice of Contraception/Barrier Requirements .........................................30
4.2.2. Collection of Retained Research Samples..................................................30
4.3. Justification for Dose ..............................................................................................30
4.4. End of Study Definition ..........................................................................................31
5. STUDY POPULATION......................................................................................................31
5.1. Inclusion Criteria.....................................................................................................31
5.1.1. All Participants ...........................................................................................31
5.1.2. Additional Inclusion Criteria for Healthy Participants with Normal 
Renal Function (Cohort 3 Only) ......................................................................32
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5.1.3. Additional Inclusion Criteria for Participants with Impaired Renal 
Function (Cohort 1 and Cohort 2 & Cohort 4 [If Applicable] Only)...............32
5.2. Exclusion Criteria....................................................................................................33
5.2.1. All Participants ...........................................................................................33
5.2.2. Additional Exclusion Criteria for Healthy Participants with Normal 
Renal Function (Cohort 3, Only) .....................................................................36
5.2.3. Additional Exclusion Criteria for Participants with Impaired Renal 
Function (Cohort 1, Cohort 2 and & Cohort 4 [If Applicable] Only)..............36
5.3. Lifestyle Considerations..........................................................................................37
5.3.1. Meals and Dietary Restrictions...................................................................37
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................37
5.3.3. Activity .......................................................................................................38
5.3.4. Contraception..............................................................................................38
5.4. Screen Failures ........................................................................................................38
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................39
6.1. Study Intervention(s) Administered........................................................................39
6.1.1. Administration............................................................................................39
6.2. Preparation, Handling, Storage, and Accountability...............................................39
6.2.1. Preparation and Dispensing........................................................................40
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................41
6.3.1. Allocation to Study Intervention ................................................................41
6.4. Study Intervention Compliance...............................................................................41
6.5. Dose Modification...................................................................................................41
6.6. Continued Access to Study Intervention After the End of the Study......................41
6.7. Treatment of Overdose............................................................................................41
6.8. Concomitant Therapy..............................................................................................42
6.8.1. Participants with Healthy Renal Function (Cohort 3 Only) .......................43
6.8.2. Participants with Impaired Renal Function (Cohort 1, and Cohorts 2 
& 4 [If Applicable]) .........................................................................................43
6.8.3. Rescue Medicine.........................................................................................43
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................43
7.1. Discontinuation of Study Intervention ....................................................................43


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7.2. Participant Discontinuation/Withdrawal From the Study.......................................44
7.2.1. Withdrawal of Consent...............................................................................44
7.3. Lost to Follow-Up ...................................................................................................45
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................45
8.1. Efficacy Assessments..............................................................................................46
8.2. Safety Assessments .................................................................................................46
8.2.1. Physical Examinations................................................................................47
8.2.2. Vital Signs ..................................................................................................47
8.2.2.1. Respiratory Rate........................................................................47
8.2.2.2. Temperature ..............................................................................48
8.2.3. Electrocardiograms.....................................................................................48
8.2.4. Clinical Safety Laboratory Assessments ....................................................49
8.2.5. COVID-19 Specific Assessments...............................................................49
8.2.6. Pregnancy Testing ......................................................................................49
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................50
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......50
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................51
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................51
8.3.2. Method of Detecting AEs and SAEs ..........................................................51
8.3.3. Follow-Up of AEs and SAEs......................................................................51
8.3.4. Regulatory Reporting Requirements for SAEs...........................................52
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................52
8.3.5.1. Exposure During Pregnancy......................................................52
8.3.5.2. Exposure During Breastfeeding ................................................54
8.3.5.3. Occupational Exposure .............................................................54
8.3.6. Cardiovascular and Death Events...............................................................55
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................55
8.3.8. Adverse Events of Special Interest.............................................................55
8.3.8.1. Lack of Efficacy........................................................................55
8.3.9. Medical Device Deficiencies......................................................................55


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8.3.10. Medication Errors.....................................................................................55
8.4. Pharmacokinetics ....................................................................................................56
8.4.1. Plasma for Analysis of PF-07321332.........................................................56
8.4.2. Urine for Analysis of PF-07321332 ...........................................................57
8.7. Immunogenicity Assessments.................................................................................58
8.8. Health Economics ...................................................................................................58
9. STATISTICAL CONSIDERATIONS ................................................................................58
9.1. Statistical Hypotheses .............................................................................................58
9.2. Analysis Sets ...........................................................................................................58
9.3. Statistical Analyses .................................................................................................59
9.3.1. Other Safety Analyses ................................................................................60
9.3.2.1. Pharmacokinetic Analyses ........................................................60
9.4. Interim Analyses .....................................................................................................61
9.5. Sample Size Determination.....................................................................................62
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................63
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............63
10.1.1. Regulatory and Ethical Considerations ....................................................63
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................63
10.1.2. Financial Disclosure .................................................................................64
10.1.3. Informed Consent Process ........................................................................64
10.1.4. Data Protection .........................................................................................65
10.1.5. Committees Structure ...............................................................................65
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10.1.5.1. Data Monitoring Committee ...................................................65
10.1.6. Dissemination of Clinical Study Data ......................................................65
10.1.7. Data Quality Assurance ............................................................................67
10.1.8. Source Documents....................................................................................68
10.1.9. Study and Site Start and Closure ..............................................................68
10.1.10. Publication Policy...................................................................................69
10.1.11. Sponsor’s Qualified Medical Personnel .................................................70
10.2. Appendix 2: Clinical Laboratory Tests .................................................................71
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................72
10.3.1. Definition of AE .......................................................................................72
10.3.2. Definition of an SAE ................................................................................73
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................74
10.3.4. Reporting of SAEs....................................................................................78
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................80
10.4.1. Male Participant Reproductive Inclusion Criteria....................................80
10.4.2. Female Participant Reproductive Inclusion Criteria.................................80
10.4.3. Woman of Childbearing Potential ............................................................81
10.4.4. Contraception Methods.............................................................................82
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......85
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................87
10.8. Appendix 8: Prohibited and Precautionary Concomitant Medications That 
May Result in DDI ....................................................................................................89
10.9. Appendix 9: Abbreviations ...................................................................................93
11. REFERENCES ..................................................................................................................98
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LIST OF TABLES
Table 1.
Renal Function Categories by eGFR Ranges ...........................................25
Table 2.
Criteria to Establish Stable Renal Function..............................................29
Table 3.
Plasma PK Parameters..............................................................................61
Table 4.
Urine PK Parameters ................................................................................61
Table 5.
Protocol-Required Safety Laboratory Assessments .................................71


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: Renal Impairment Study of PF-07321332
Rationale
The purpose of this study is to characterize the effect of renal impairment on the plasma PK 
of PF-07321332/ritonavir. Findings from this study will be used to develop dosing 
recommendations so that the dose and/or dosing interval may be adjusted appropriately in the 
presence of renal disease.
Objectives and Endpoints
Objectives
Endpoints
Primary:
Primary:

Part 1: To evaluate the effect of mild (if 
applicable) and moderate renal impairment on 
the PK of PF-07321332, following a single 
oral dose administration of PF-07321332 
pharmacokinetically boosted with ritonavir.

Part 2: To evaluate the effect of severe renal 
impairment on the PK of PF-07321332, 
following a single oral dose administration of 
PF-07321332 pharmacokinetically boosted 
with ritonavir.

Plasma PF-07321332 PK parameters: Cmax, 
AUCinf (or AUClast if AUCinf cannot be reliably 
estimated)

Urine PF-07321332 PK parameters: Ae, CLr, if 
applicable and as data permit
Secondary: 
Secondary: 

To evaluate the safety and tolerability of 
PF-07321332 and ritonavir, following a single 
oral dose administration of PF-07321332 
pharmacokinetically boosted with ritonavir, in 
participants with renal impairment and in 
healthy participants with normal renal 
function.

To characterize additional PK parameters of 
PF-07321332 following a single oral dose of 
PF-07321332 pharmacokinetically boosted 
with ritonavir by renal function.

Safety: treatment-emergent adverse events, 
clinical laboratory tests, vital signs, physical 
examination, and ECGs.

Plasma PF-07321332 PK parameters: C12, C24, 
Tmax, AUClast, CL/F, Vz/F, and t½, as data permit.
Overall Design
Brief Summary
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal 
impairment on the plasma and urine (if applicable) PK, safety and tolerability of a single oral 


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Final Protocol Amendment 2, 08 July 2021 
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dose of PF-07321332 in combination with the PK boosting agent ritonavir in approximately 
32 participants. Part 1 will be conducted in participants with stable mild or moderate renal 
impairment and a control group of participants with normal renal function. Part 2 will be 
conducted in participants with stable severe renal impairment. A staged approach will be 
followed in the study. Part 1 participants from the moderate renal impairment group 
(Cohort 1) will be recruited first. Enrollment into the mild renal impairment group (Cohort 2)
will initiate, if necessary, after preliminary analysis of PK and safety data from at least 
2 participants with moderate renal impairment have been reviewed. The healthy participants 
(Cohort 3) will be recruited later such that each participant’s age is within ±10 years and 
weight is within ±15 kg of the mean of the groups of participants with renal impairment
group. The decision to conduct Part 2 will be made based on results from Part 1. Enrollment 
into Part 2 will not commence until preliminary analysis of PK and safety data from at least 
2 participants with moderate renal impairment have been reviewed.
All participants in both normal and renal impairment groups will provide informed consent 
and undergo Screening evaluations to determine their eligibility. Participants will be selected 
and categorized into normal renal function or renal impairment groups based on their eGFR 
(using the CKD-EPI equation).
Eligible participants will be admitted to the CRU on Day -1 (at least 12 hours prior to the 
dosing of PF-07321332 on Day 1) and will be confined in the CRU until Day 3. On the 
evening of Day -1, participants will receive a single 100 mg dose of ritonavir (-12 hour 
relative to PF-07321332 dosing). On the morning of Day 1, the participants will receive a 
single dose of 100 mg PF-07321332 with a 100 mg dose of ritonavir after a fast of at least 
10 hours. Ritonavir, 100 mg, will continue to be dosed at 12 and 24 hours post PF-07321332 
dosing to ensure maintenance of the PK boosting effect. Serial blood and urine samples at 
specified intervals will be collected up to 48 hours post-dose for plasma and urine PK 
assessments. 
Safety assessments will be performed during Screening, on Day -1 prior to dosing, Day 1, 
and on Day 3. Physical examinations, vital sign measurements, and clinical laboratory tests 
will be conducted, and AEs will be monitored to assess safety. The total participation time 
(eg, CRU confinement time for study procedures) for each participant in this study is 
approximately 3 nights/4 days (excluding screening & Follow-Up contact). 
A safety follow-up call will be made to participants 28 to 35 days from administration of the 
last dose of study intervention.
Number of Participants
Approximately 36 participants may be enrolled to study intervention.
Note: "Enrolled" means a participant's, or his or her legally authorized representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process and screening. A participant will be considered enrolled if the informed consent is 
not withdrawn prior to participating in any study activity after screening. Potential 


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participants who are screened for the purpose of determining eligibility for the study, but do 
not participate in the study, are not considered enrolled, unless otherwise specified by the 
protocol.
Intervention Groups and Duration
Each enrolled participant will receive a single 100 mg dose of PF-07321332 administered 
orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at 
-12, 0, 12, and 24 hours relative to PF-07321332 dosing. 
The total planned duration of participation, from the Screening visit to the last Follow-up 
phone call, is approximately up to 9 weeks.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
ANOVA will be used to compare the natural log transformed AUCinf (or AUClast if AUCinf 
cannot be reliably estimated) and Cmax for PF-07321332 between normal renal function 
group (Reference) and impaired renal function groups (Test). Estimates of the adjusted mean 
differences (Test-Reference) and corresponding 90% CI will be obtained from the model. 
The adjusted mean differences and 90% CIs for the differences will be exponentiated to 
provide estimates of the ratio of the adjusted geometric means (Test/Reference) and 90% CIs 
for the ratios.
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.
Visit Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Follow-up
Contact
Early Termination/
Discontinuation 
(DC)
Day -28 to Day -2
Days Relative to Day 1
Abbreviations used in this table 
can be found in Appendix 9
S1
S2
28-35 Daysc
Informed consent
X
Admission to CRU
X
Confinement to CRU
X
→
→
X
Inclusion/exclusion criteria
X
X
Medical history 
X
X
Demographyd
X
Physical examinatione
X
X
X
X
Height and weight assessmentf
X
X
X
Xg
Safety laboratory tests (blood and 
urine)h
X
Xi
X
X
Xg
X
eGFR assessmentj
X
X
X
Xg
Illegal drug/tobacco/alcohol use
X
X
Urine alcohol test or alcohol 
breath test
X
X
Urine or serum pregnancy test 
(WOCBP only)
X
X
X
X
Contraception checkk
X
X
X
X
X
X
Serum FSH in post-menopausal 
females amenorrheic ≥12 months 
and under 60 years of age
X
Urine drug screen
X
X
Single supine 12-Lead ECG
X
X
X
X


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Visit Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Follow-up
Contact
Early Termination/
Discontinuation 
(DC)
Day -28 to Day -2
Days Relative to Day 1
Abbreviations used in this table 
can be found in Appendix 9
S1
S2
28-35 Daysc
Vital signs (supine BP, 
respiratory rate, pulse rate) and 
temperature
X
X
X
X
HIV, HBsAg, HBcAb, HCVAb 
testingl
X
PF-07321332 administration
X
Ritonavir administrationm
X
X
X
Plasma PK for PF-07321332
X
X
X
X
Urine PK for PF-07321332 
X
X
X
 
Prior/concomitant treatments
X
X
X
→
→
X
X
X
COVID-19 testingo
X
X
X
COVID-19 check temperaturep
X
X
X
X
X
X
COVID-19 questionnaireq
X
CRU discharge 
X
Serious and nonserious adverse 
event monitoring
X
X
X
→
→
X
X
X
a.
Day relative to start of PF-07321332 dosing (Day 1).
b.
Screening will consist of 2 CRU outpatient visits (S1 and S2) between 3 to 14 days apart, with the first screening visit occurring within 28 days prior to investigational 
product administration (Day 1). The second screening visit is only to demonstrate stable renal function with difference between eGFRs at S1 and S2 required to be ≤25% of 
the value obtained at S1. If participant meets all screening criteria at S2 visit, and Day -1 visit can be performed immediately, the participant may be admitted to the unit at 
conclusion of S2 visit. Other screening procedures completed during S1 do not need to be repeated. See Section 4.1 for outpatient visit screening schedule.
c.
Contact may occur via telephone contact and must occur 28 to 35 days from the last administration of ritonavir or from the time of early termination/discontinuation. If 
participant demonstrates an increase of >25% in serum creatinine from Day -1 to Day of discharge, he or she will be asked for a follow-up visit to collect eGFR.
d.
Demographics will include race, age, and gender.
e.
Complete physical examination at screening (normal renal function; Cohort 3 is at screening only only), Day -1, Day 3, and early termination. Brief physical examination at 
any time point as deemed necessary by the investigator.
f.
Height to be obtained at S1 only, weight to be obtained at S1, S2 and Day -1.
g.
Only when the participant demonstrates an increase of >25% in serum creatinine from Day -1 to Day of discharge. Only serum creatinine and weight information will be 
collected for eGFR assessment. 
h.
Safety laboratory assessments include chemistry, hematology, and urinalysis (and microscopy, if needed) and will be performed at Screening, Day -1, Day 3, and early 
termination day. All the assessments must be collected following at least a 4 hour fast. 
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Visit Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Follow-up
Contact
Early Termination/
Discontinuation 
(DC)
Day -28 to Day -2
Days Relative to Day 1
Abbreviations used in this table 
can be found in Appendix 9
S1
S2
28-35 Daysc
i.
Only serum creatinine will be assessed on S2 for eGFR assessment.
j.
To confirm eligibility, participants must have stable renal function defined as ≤25% difference for eGFR values at S2 compared to the value at S1. The average of the 
2 screening eGFR values will be used for participant stratification and group assignment (provided stable renal function is still demonstrated). If the renal function stability 
criterion is met but the renal function classification category changes between S1 eGFR and the average of the S1 and S2 eGFRs, the eGFR measurement at Day -1 will 
also be used to determine the appropriate group classification category using an average of all 3 eGFR values, to determine whether the participant will be eligible for 
enrollment. The Day -1 eGFR value will be used for PK analysis. The eGFR determination will utilize the 4-variable CKD-EPI method. A follow-up eGFR will be 
collected at Day 28 (with window of +3 days to allow for holidays) for any participant who demonstrates an increase of >25% in serum creatinine from Day -1 to Day of 
discharge. Serum creatinine laboratory test may be repeated once to confirm results at the discretion of the investigator; the last value will be used to calculate eGFR.
k.
Confirmation of appropriate use only.
l.
HBsAb will be performed as reflex testing for any participant who is HBsAg negative and HBcAb positive (Section 10.2). HCV RNA will be performed as reflex testing 
for any participant who is HCV Ab positive (Section 10.2).
m.
Ritonavir will be administered on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing.
 
o.
Testing for COVID-19 pathogen by RT-PCR will be performed prior to being admitted to the clinic for confinement, on S1, S2, and Day -1 (only 1 test needed if S2 = 
Day -1), and if participant develops COVID-19 like symptoms.
p.
To be done at least daily during residence. On days in which vitals are being collected, temperature will only need to be taken once and documented. 
q.
Check exposure to positive case, residence or travel in area of high incidence and COVID-19 related signs and symptoms.
Pharmacokinetic Sampling Schema
Study Day
-1
1
2
3
Hours Before/After Dose
-12
0a
0.5
1
2
3
4
6
8
10
12
24
36
48
PF-07321332 administration
X
Ritonavir administration
X
X
X
X
PK blood samplingb
X
X
X
X
X
X
X
X
X
X
X
X
X
PK urine collectionc
X
→
→
→
→
→
→
→
→
→
X
→
X
a.
Predose PF-07321332 and ritonavir sample collection.
b.
Blood samples are to be collected for plasma PK assessment of PF-07321332.
c.
Urine collections during intervals of ≤24, and >24 and ≤48 hours after PF-07321332 dosing on Day 1. During the designated urine collection intervals ([0-24], and [24-48] 
hours post dose), participants will void ALL urine produced during the designated collection interval, including a forced void at the end of the collection interval, directly 
into pre weighed urine collection container. Urine samples will be analyzed using a validated analytical method in compliance with Pfizer SOPs, only if it is determined by 
the study team that there is a need to do so, based on review of PF-07321332 plasma PK results.
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2. INTRODUCTION
PF-07321332 is a potent and selective inhibitor of the SARS-CoV-2 3CL protease that is 
currently being developed as an oral treatment of COVID-19. Ritonavir is a strong CYP3A4 
inhibitor being used to inhibit the metabolism of PF-07321332 in order to increase plasma 
concentrations of PF-07321332 to values that are anticipated to be efficacious.
2.1. Study Rationale 
In vitro and in vivo metabolite profiling suggests that the primary clearance mechanism for 
PF-07321332 is CYP3A4 mediated oxidation. In a reaction phenotyping study using human 
liver microsomes in the presence of selective CYP inhibitors, CYP3A4 was predicted to be 
the major contributor (fm = 0.99) to the in vitro oxidative metabolism of PF-07321332. As 
such, in the FIH study, C4671001, the CYP3A4 inhibitor ritonavir was used to enhance the 
exposure of PF-07321332 in order to achieve plasma levels that are anticipated to be 
efficacious. Preliminary PK data following multiple oral administrations of 
PF-07321332/ritonavir at doses of 75/100 mg, 250/100 mg, and 500/100 mg q12h suggest 
that the renal pathway may play a significant role in PF-07321332 excretion when 
co-administered with ritonavir, with approximately 32.5% (PF-07321332/ritonavir 
500/100 mg) to 64.6% (PF-07321332/ritonavir 75/100 mg) of the drug excreted unchanged 
in urine across doses at steady-state, and renal clearance ranging between 3.5 to 4.4 L/h 
across doses. 
PF-07321332/ritonavir is intended for short term (eg, 5 day) use, in patients with COVID-19,
some of whom may have some degree of impaired renal function. Therefore, the purpose of 
this study is to characterize the effect of renal impairment on the plasma PK of 
PF-07321332/ritonavir. Findings from this study will be used to develop dosing 
recommendations so that the dose and/or dosing interval may be adjusted appropriately in the 
presence of renal disease.
2.2. Background 
In December 2019, COVID-19 was identified as a new, potentially fatal, respiratory infection 
caused by the novel coronavirus, SARS-CoV-2. The WHO declared COVID-19 a Public 
Health Emergency of International Concern on 20 January 2020 and further characterized the 
disease outbreak as a pandemic on 11 March 2020.1
PF-07321332 is an orally bioavailable 3CLpro inhibitor shown to be effective against 
SARS-CoV-2 3CLpro (Ki = 0.00311 µM) in a biochemical enzymatic assay. Since the 
3CLpro from human coronaviruses are structurally similar and share a high degree of 
conservation at the active site of the enzyme, the ability of PF-07321332 to inhibit the 3CLpro
of other coronaviruses (SARS-CoV-1 and HCoV-229E, MERS, HCoV-OC43, HCoV-HKU1, 
and HCoV-NL63) was also confirmed, indicating a potential for broad spectrum 
anti-coronavirus activity. The coronavirus 3CL protease is a virally encoded enzyme that is 
critical to the SARS-CoV-2 replication cycle, analogous to other obligatory virally encoded 
proteases (eg, HIV Protease, HCV Protease).2 PF-07321332 is being developed as an oral 
treatment in patients with COVID-19 infection. 


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Ritonavir is a strong CYP3A4 inhibitor being used to inhibit the metabolism of PF-07321332 
in order to increase plasma concentrations of PF-07321332 to values that are anticipated to 
be efficacious. Ritonavir is not expected to have any pharmacological impact on the 
SARS-CoV-2 virus and its elimination is not expected to be significantly altered by renal 
impairment. Ritonavir and is being used only as a pharmacokinetic boosting agent.
2.2.1. Nonclinical Pharmacology
Details of the nonclinical pharmacology of PF-07321332 can be found in the current IB.3
2.2.2. Nonclinical Pharmacokinetics and Metabolism
Hepatic CYP3450 enzymes were identified as the main pathway for clearance of 
PF-07321332 in vitro in liver microsomes (mouse, rat, hamster, rabbit, monkey, and human), 
hepatocytes (rat, monkey, and human), and in vivo in rat and monkey after repeat oral dosing 
(Study PF-07321332_09Nov20_084546). In a reaction phenotyping study using human liver 
microsomes in the presence of selective CYP inhibitors, CYP3A4 was predicted to be the 
major contributor (fm = 0.99) to the in vitro oxidative metabolism of PF-07321332. No 
significant CYP3A5 contribution is expected to the metabolism of PF-07321332 (Study 
PF-07321332_21Nov20_072016). Urinary excretion of PF-07321332 following single IV or 
oral doses in rats was approximately 11%, suggesting minor urinary contributions to the 
overall elimination of PF-07321332. 
Additional information of the nonclinical PK and metabolism of PF-07321332 is available in 
the current IB.3
2.2.3. Nonclinical Safety
There were no adverse findings observed in repeat-dose toxicity studies in rats and monkeys 
up to 2 weeks duration and the NOAELs were the highest dose administered (1000 mg/kg 
and 600 mg/kg in the rat and monkey studies, respectively). PF-07321332-related 
 non-adverse, test article-related clinical findings included sporadic occurrence of emesis 
with slight body weight decreases in monkeys. Monitorable and reversible clinical pathology 
findings included those possibly suggestive of low-grade inflammation (in rats and monkeys) 
or alterations in the coagulation pathways (in rats only) without clinical or microscopic 
correlates. Other non-adverse clinical pathology findings were likely due to the emesis and 
subsequent dehydration in monkeys. In rats administered 1000 mg/kg/day, lower mean 
absolute and relative heart weights (females) and higher absolute and relative liver weights 
(both sexes) were observed relative to controls. The lower heart weights had no microscopic 
correlates and were fully reversed at the end of the 2-week recovery period. Higher liver 
weights correlated with reversible, non-adverse microscopic findings of minimal to mild 
severity in the liver and thyroid gland consistent with adaptive changes related to microsomal 
enzyme induction.
PF-07321332 was not mutagenic or clastogenic in in vitro genetic toxicity studies and was 
negative in the in vivo rat micronucleus assay incorporated into the GLP repeat-dose rat 
toxicity study. 


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The nonclinical studies performed adequately support the oral administration of 
PF-07321332 in the clinic for up to 14 days. 
Further details of the nonclinical safety program are provided in the current IB.3
2.2.4. Clinical Overview
Safety, tolerability and pharmacokinetics of PF-07321332 in healthy adult participants is 
currently being explored in an ongoing Phase 1 FIH study (C4671001). Study C4671001 is a 
3-part study consisting of SAD (PART-1), MAD (PART-2), and relative bioavailability/food 
effect (PART-3) evaluations. PART-1 and -2 are randomized, double-blind, sponsor-open, 
and placebo controlled to evaluate safety, tolerability, and PK of single and multiple 
escalating oral doses of PF-07321332, respectively. PART-3 is randomized and open-label to 
evaluate relative bioavailability and food effect of an oral tablet formulation.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.3. Benefit/Risk Assessment
PF-07321332/ritonavir is not expected to provide any clinical benefit to healthy participants
or participants with renal impairment in this study. This study is designed primarily to
characterize the effect of renal impairment on the plasma PK of a single dose of 
PF-07321332 pharmacokinetically enhanced with ritonavir. The data from this study are 
expected to provide the basis for development of dosing recommendations for target patient 
populations who may have renal impairment.
 
 
 
 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-07321332 with ritonavir may be found in the IB3 and ritonavir 
USPI4, which are the SRSDs for this study. 
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): PF-07321332
Emesis
Sporadic emesis were observed at ≥100 mg/kg/day of 
PF-07321332 in the 15-day NHP toxicology study (See IB). 
Based on preliminary data, no emesis was observed in the 
FIH study C4671001 at single doses of PF-07321332 up to 
1500 mg alone and up to 750 mg administered with ritonavir 
(100 mg at -12h, 0h, 12h), and at repeated daily doses 
administered orally for 10 days of up to 500 mg 
PF-07321332 BID with 100 mg ritonavir BID.
As this is an investigational agent, there is some 
risk that is mitigated by close observation of AEs, 
etc. If needed, palliative care or antiemetics may 
be provided.
Neuronal and pulmonary effects
Transient effect in rat neuronal and pulmonary endpoints 
were observed in rat toxicology study at the high dose level 
(1000 mg/kg as single dose; See IB). Based on preliminary 
data, no AEs suggestive of neuronal or pulmonary effects 
were observed in the FIH study C4671001 at single doses of 
PF-07321332 up to 1500 mg alone and up to 750 mg 
administered with ritonavir (100 mg at -12h, 0h, 12h), and at 
repeated daily doses administered orally for 10 days of up to 
500 mg PF-07321332 BID with 100 mg ritonavir BID.
Vital signs, including respiratory rate, will be 
monitored for pulmonary effect. There will be 
close observation of AEs for any signs of 
neuronal effect.  
Hemodynamic effects
Low level inflammation (increase in fibrinogen) in 15-day 
NHP toxicology study and changes in platelets, globulin and 
albumin/globulin ratio and coagulation system (increase in 
PT and aPTT) in 14-day rat toxicology study (See IB). No 
relevant laboratory changes in inflammatory markers have 
been observed in the FIH study C4671001 at single doses of 
PF-07321332 up to 1500 mg alone and up to 750 mg 
administered with ritonavir (100 mg at -12h, 0h, 12h), and at 
repeated daily doses administered orally for 10 days of up to 
500 mg PF-07321332 BID with 100 mg ritonavir BID.
Fibrinogen, platelets, PT and aPTT, albumin and 
total proteins will be monitored. 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Thyroid function studies
In 14 day rat toxicology study at high dose of PF-07321332 
(1000 mg/kg/day) thyroid gland changes observed were of 
low severity and without evidence of tissue damage. In the 
FIH study C4671001, 3 participants had TEAEs of elevated 
TSH levels across treatment groups (PF-07321332 or 
placebo with ritonavir 100 mg BID) in the MAD part of the 
study. There was no clinical correlation with these TSH 
changes and free T4 remained within reference range at all 
times.
TSH and free T4 will be evaluated to monitor 
thyroid function
Study Intervention(s): Ritonavir
Gastrointestinal disturbances (including 
diarrhea, nausea, vomiting and 
abdominal pain).
Frequently reported adverse reaction in HIV patients at 
600 mg BID.
Lower dose of 100 mg twice daily is used in this 
study. There will be close observation of AEs. If 
needed, anti-emetics may be provided. 
Neurological disturbances (eg, 
paresthesia, including oral paresthesia, 
dysgeusia and dizziness).
Frequently reported adverse reaction in HIV patients at 
600 mg BID.
Lower dose used in this study. There will be close 
observation of AEs.  
Rash (most commonly reported as 
erythematous and maculopapular, 
followed by pruritic).
Frequently reported adverse reaction in HIV patients at 
600 mg BID.
Lower dose used in this study. There will be close 
observation of AEs and monitoring through 
targeted physical exams. If needed, palliative care 
may be provided. 
Fatigue/Asthenia
Frequently reported adverse reaction in HIV patients at 
600 mg BID.
Lower dose used in this study. There will be close 
observation of AEs and monitoring through 
targeted physical exams.
Limited case reports of renal toxicity
Although ritonavir therapy is not generally considered 
nephrotoxic, a limited number of cases of acute kidney 
injury secondary to ritonavir have been reported post-
marketing in HIV patients.
Lower dose used in this study. There will be close 
observation of AEs and renal function.


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2.3.2. Benefit Assessment
PF-07321332/ritonavir will not provide any clinical benefit to healthy participants or 
participants with renal impairment in this study. Any anticipated benefit to participants 
would be in terms of contribution to the process of developing a new therapy in an area of 
unmet medical need.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with PF-07321332/ritonavir are justified by the anticipated benefits 
that may be afforded to participants with COVID-19.
3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary:
Primary:

Part 1: To evaluate the effect of mild (if 
applicable) and moderate renal impairment on 
the PK of PF-07321332, following a single 
oral dose administration of PF-07321332 
pharmacokinetically boosted with ritonavir.

Part 2: To evaluate the effect of severe renal 
impairment on the PK of PF-07321332, 
following a single oral dose administration of 
PF-07321332 pharmacokinetically boosted 
with ritonavir.

Plasma PF-07321332 PK parameters: Cmax, 
AUCinf (or AUClast if AUCinf cannot be reliably 
estimated)

Urine PF-07321332 PK parameters: Ae, CLr, if 
applicable and as data permit
Secondary: 
Secondary: 

To evaluate the safety and tolerability of 
PF-07321332 and ritonavir, following a single 
oral dose administration of PF-07321332 
pharmacokinetically boosted with ritonavir, in 
participants with renal impairment and in 
healthy participants with normal renal 
function.

To characterize additional PK parameters of 
PF-07321332 following a single oral dose of 
PF-07321332 pharmacokinetically boosted 
with ritonavir by renal function.

Safety: treatment-emergent adverse events, 
clinical laboratory tests, vital signs, physical 
examination and ECGs.

Plasma PF-07321332 PK parameters: C12, C24, 
Tmax, AUClast, CL/F, Vz/F, and t½, as data permit.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal 
impairment on the plasma and urine (if applicable) PK, safety and tolerability of a single oral 
dose of PF-07321332 in combination with the PK boosting agent ritonavir in approximately 


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36 participants. Part 1 will be conducted in approximately 24 adult male and female 
participants with stable mild or moderate renal impairment and a control group of 
participants with normal renal function. Part 2 will be conducted in approximately 8 adult 
male and female participants with stable severe renal impairment. A staged approach, as 
outlined in detail below, will be followed in the study.
Participants will be selected and categorized into normal renal function or renal impairment 
groups based on their eGFR as shown in Table 1.
Table 1.
Renal Function Categories by eGFR Ranges
Cohort
Renal Impairmenta
Estimated eGFRb (mL/min)
Number of Participants
1
Moderate Renal Impairment
≥30 to <60
8
2
Mild Renal Impairment
60 – <90
8
3
None (Normal)
≥90
8 (up to 12)
4
Severe Renal Impairment
<30 and not requiring dialysis
8
a.
Stages of renal impairment are based on Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical 
Practice Guidelines for Chronic Kidney Disease (CKD).5
b.
Estimate of eGFR based on CKD-EPI formula. The average of the 2 screening eGFR value will be used for 
group assignment.
Part 1: Approximately 24 participants will be enrolled in Part 1; approximately 
8 participants with moderate renal impairment (Cohort 1), approximately 8 with mild renal 
impairment (Cohort 2), and approximately 8 (up to 12) with normal renal function 
(Cohort 3), to ensure at least 6 evaluable participants in each group. Participants from the 
moderate renal impairment group (Cohort 1) will be recruited first. Enrollment into Cohort 2 
will initiate, if necessary (see criteria below), after preliminary analysis of PK and safety data 
from at least 2 participants with moderate renal impairment have been reviewed. The healthy 
participants (Cohort 3) will be recruited later such that each participant’s age is within 
±10 years and weight is within ±15 kg of the mean of participants within the renal 
impairment groups. An attempt will be made to maintain a similar male/female ratio 
composition between groups. Care will be taken when recruiting the healthy participants 
such that the entire group is not of substantially different age or of substantially different
body weight than the moderate renally impaired participants. Approval from the sponsor 
must be obtained before proceeding with dosing healthy participants with normal renal 
function.
Participants with stable mild and moderate renal impairment and control participants with 
normal renal function will receive a single 100 mg dose of PF-07321332 administered orally 
in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 
12, and 24 hours relative to PF-07321332 dosing. Blood and urine samples will be collected 
for measurement of plasma and urine concentrations of PF-07321332 as per SoA. 
If there are participants who withdraw or discontinue treatment from the normal or mild or 
moderate renal impairment groups and who are considered to be non-evaluable with respect 
to the primary PK objective, additional participants can be enrolled at the discretion of the 
sponsor.


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Criteria to enroll Cohort 2: After preliminary evaluation of results from participants with 
moderate renal impairment (Cohort 1), enrollment of participants with mild renal impairment 
(Cohort 2) may be initiated. Cohort 2 will be conducted if the estimate of the ratio of 
PF-07321332 AUCinf for the moderate renal impairment group compared to healthy normals 
is ≥1.5.  
Part 2: The decision to conduct Part 2 will be made based on results from Part 1. Enrollment 
into Part 2 will not commence until preliminary analysis of PK and safety data from at least 
2 participants with moderate renal impairment have been reviewed. Approximately 
8 participants with severe (Cohort 4) renal impairment will be enrolled to ensure at least 
6 evaluable participants in each group. As in Part 1, renal impairment classification will be 
based on eGFR. Participants will receive a single 100 mg dose of PF-07321332 administered 
orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at 
-12, 0, 12, and 24 hours relative to PF-07321332 dosing. Blood and urine samples will be 
collected for measurement of plasma and urine concentrations of PF-07321332 as per SoA.
Healthy participants from Part 1 will be used as the control group for the severe impairment 
participants. If necessary, additional participants may be enrolled into the normal renal 
function group to ensure adequate matching; however the total number will not exceed 12.
The dose of PF-07321332 may be reduced for participants with severe renal disease if 
considered necessary by the investigator and sponsor to ensure participant safety. Similarly, 
the timings of sample collection may be adjusted during study conduct on the basis of 
emerging data in order to allow optimal characterization of the PK profile, eg, additional 
post-dose sample collection may be introduced, etc. 
When recruiting the Part 2 participants, attempts to match the entire group to the participants 
in Part 1 with respect to age, gender and body weight will be made. Other demographics, 
such as race and ethnicity, may be considered for matching the Part 1 and Part 2 populations 
when possible. Statistical considerations to account for any differences in demographics are 
detailed in Section 9.3.
As in Part 1, if there are participants who withdraw or discontinue treatment from the severe 
impairment group and who are considered to be non-evaluable with respect to the primary 
PK objective, additional participants can be enrolled at the discretion of the sponsor. 
For both Parts 1 and 2: All participants in both normal and renal impairment groups will 
provide informed consent and undergo Screening evaluations to determine their eligibility. 
Participant screening for participation in this study will consist of 2 CRU outpatient visits not 
more than 14 days apart (but at least 3 days apart), with the first screening visit occurring 
within 28 days prior to administration of investigational product. An eGFR value for group 
placement (provided stable renal function is still demonstrated) will be obtained by the 
average of the 2 screening values (using the CKD-EPI equation). If the renal function 
stability criterion is met but the renal function classification category changes between S1 
eGFR and the average of the S1 and S2 eGFRs, the eGFR measurement at Day -1 will also 
be used to determine the appropriate group classification category using an average of all 
3 GFR values, to determine whether the participant will be eligible for enrollment. 


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Eligible participants will be admitted to the CRU on Day -1 (at least 12 hours prior to the 
dosing of PF-07321332 on Day 1) and will be confined in the CRU until Day 3. If participant 
meets all screening criteria at S2 visit, and Day -1 visit can be performed immediately, the 
participant may be admitted to the unit at conclusion of S2 visit. 
On the evening of Day -1, participants will receive a single 100 mg dose of ritonavir (-12 hr 
relative to PF-07321332 on Day 1). On the morning of Day 1, the participants will receive a 
100 mg single dose of PF-07321332 with a 100 mg dose of ritonavir after a fast of at least 
10 hours. No food will be allowed for at least 4 hours post-dose. Ritonavir, 100 mg, will 
continue to be dosed at 12 and 24 hours post PF-07321332 dosing to ensure maintenance of 
the PK boosting effect. Serial blood and urine samples at specified intervals (as per SoA) will 
be collected for 48 hours post-dose for plasma and urine PK assessments, prior to discharge 
from the CRU on Day 3. The eGFR value determined on Day -1 will be used for PK analysis. 
Safety assessments (as specified in the SoA) will be performed during S1, on Day -1 prior to 
dosing, Day 1, and on Day 3. Only serum creatinine will be additionally assessed on S2 for 
eGFR estimation. Physical examinations, vital sign measurements, and clinical laboratory 
tests will be conducted and AEs will be monitored as per SoA to assess safety. The total 
participation time (ie, CRU confinement time for study procedures) for each participant in 
this study is approximately 3 nights/4 days (excluding screening & Follow-Up contact). 
Participants will have a follow-up phone contact 28-35 days after last- ritonavir 
administration or from the time of early termination/discontinuation to assess for AEs. If 
participant demonstrates an increase of >25% in SCr from Day -1 to Day of discharge, he or 
she will be asked for a follow-up visit to collect eGFR. The total planned duration of 
participation, from the Screening visit to the last Follow-up phone call, is approximately up 
to 9 weeks.
All procedures and their timelines follow the SoA.
Calculation of eGFR:
The following CKD-EPI equation will be used to calculate eGFR (Scr, std denotes serum 
creatinine measured with a standardized assay for serum creatinine):
If female and SCr is ≤0.7 mg/dL:
eGFR (mL/min/1.73 m2) = 144 × (SCr, std/0.7) – 0.329 × 0.993age (× 1.159, if Black)
If female and SCr is >0.7 mg/dL:
eGFR (mL/min/1.73 m2) = 144 × (SCr, std /0.7) – 1.209 × 0.993age (× 1.159, if Black)
If male and SCr is ≤0.9 mg/dL:
eGFR (mL/min/1.73 m2) = 141 × (SCr, std /0.9) – 0.411 × 0.993age (× 1.159, if Black)


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If male and SCr is >0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr, std /0.9) – 1.209 × 0.993age (× 1.159, if Black)
Note that the value of eGFR, which is directly obtained from the laboratory or calculated 
using the equation above, is generally normalized to an average body size of 1.73 m2 for 
diagnosis, prognosis and treatment of renal disease. In terms of clearance of renally filtered 
drugs (including secreted drugs), renal elimination capacity is related to absolute GFR 
in mL/min. To use the CKD-EPI-derived, BSA-adjusted value of eGFR to obtain absolute 
GFR (mL/min) for renal disease classification or participant assignment into different renal 
disease groups, this value should be multiplied by the individual participant’s BSA 
(ie, measured BSA/1.73 m2). The BSA of an individual can be calculated by the following
formula as described below:
BSA = (Weight0.425 × Height0.725) × 0.007184
In summary, GFR in mL/min calculated as below will be used for renal impairment group 
placement: 
Step 1: Obtain the CKD-EPI-derived eGFR:
Step 2: Convert the CKD-EPI-derived, BSA-adjusted eGFR obtained above to absolute 
GFR (mL/min) for eligibility assessment using the following equation: 

eGFR (mL/min) = eGFR (mL/min/1.73m2) × participant’s BSA, where BSA is 
calculated as BSA = (Weight0.425 × Height0.725) × 0.007184.
CLCR will also be estimated from a spot serum creatinine measurement using the following 
C-G equation:
CLCR (mL/min) = (140 – age [years]) × total body weight (kg) × (0.85 for females)
72 × serum creatinine (mg/dL)
Note that eGFR calculated by the CKD-EPI equation will be used for categorization of 
degrees of renal impairment. Nevertheless, renal function will be estimated using both C-G 
and CKD-EPI equations in this study and dose recommendations will be made using both 
C-G and CKD-EPI equations.
To be enrolled into the study, participant must demonstrate stable renal function, 
with ≤25% change based upon screening S1 eGFR and screening S2 eGFR (calculated by the 
CKD-EPI equation). The S2 eGFR assessment should be performed between 3 to 14 days 


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after the S1 eGFR assessment. The average of these 2 eGFR values will be used for group 
placement based on the renal function classification category.

If the renal function stability criterion is met and the renal function classification 
category remains the same between S1 eGFR and the average of the S1 and 
S2 eGFRs, participant will be eligible for enrollment.

If the renal function stability criterion is not met, participant will be screen failed.

If the renal function stability criterion is met but the renal function classification 
category changes between S1 eGFR and the average of the S1 and S2 eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether 
the participant will be eligible for enrollment. 
In case of screen failure related to eGFR stability and/or change in the renal function 
classification category, participant may be re-screened once after a 30-day period, provided 
that the initial screen failure is not due to an Inclusion/Exclusion criterion that results in 
permanent disqualification from enrollment (eg, medical history). This can be done only with 
sponsor’s approval.
Please see Table 2 below regarding demonstration of stable renal function:
Table 2.
Criteria to Establish Stable Renal Function
Renal function Measurement
eGFR (mL/min)
Criterion for stability
S1
G1
N/A
S2 (Within 3 to 14 days after S1)
G2
=|G2-G1|×100/G1a
If ≤25%; stable
If >25%; not stable
a.
Parenthesis of | | represents absolute values.
Serum creatinine laboratory test may be repeated once to confirm results at the discretion of 
the investigator; the last value will be used to calculate eGFR.
4.2. Scientific Rationale for Study Design
This study is a Phase 1, non-randomized, open-label study of PF-07321332 in participants 
with mild and moderate renal impairment and participants with normal renal impairment, 
matched for age, body weight and, to the extent possible, for gender composition (Part 1), 
and in participants with severe renal impairment (Part 2). Details on age and body weight 
matching criteria are specified in Section 4.1. 
PF-07321332 alone is thought to be primarily eliminated through a CYP450 mediated 
oxidation with CYP3A4 as the major contributor (fm = 0.99) and renal excretion as 
unchanged a minor component. However, in the presence of the CYP3A4 inhibitor ritonavir, 
preliminary data suggests renal excretion may play a significant role in PF-07321332 


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excretion. Based on preliminary population PK modeling, mild renal impairment is predicted 
to have a minor impact on exposure of PF-07321332 (<15% increase in Cmax and AUC). 
Therefore, the effect of renal impairment on PF-07321332 PK will be initially evaluated in 
moderate renal impairment, the renally impaired population more likely to be of impact. If 
the study results demonstrate that moderate renal impairment does not alter PK to an extent 
that warrants dosage adjustment (See Section 4.1, Criteria to enroll Cohort 2), mild renal 
impairment will not be evaluated. If the results do not support such a conclusion, enrollment 
will open to mild renal impairment. The decision to conduct Part 2, in participants with 
severe renal impairment, will also be based on results from moderate renal impairment 
participants from Part 1. More specifically, if data from Part 1 supports the use of population 
PK modelling to predict drug exposures in participants with severe renal impairment, the 
study may stop after Part 1. 
A single dose of PF-07321332 was selected and is considered appropriate as available data 
do not indicate PF-07321332 PK are time-dependent, and hence, single dose data are 
considered predictive of steady state. As ritonavir is not eliminated renally, multiple doses of 
100 mg ritonavir will be administered at -12, 0, 12 , and 24 hours relative to PF-07321332 
dosing to ensure adequate PK boosting effect over the duration of PF-07321332 exposure. 
PF-07321332 is not extensively bound to human plasma proteins, with fu of 0.31 observed in 
the in vitro protein binding study. Thus, no additional blood samples will be collected in this 
study for ex vivo protein binding analysis. 
4.2.1. Choice of Contraception/Barrier Requirements 
Human reproductive safety data are limited for PF-07321332, 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).
4.2.2. Collection of Retained Research Samples
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
A single oral dose of 100 mg PF-07321332, pharmacokinetically enhanced with ritonavir
(100 mg at -12, 0, 12, and 24 hours relative to PF-07321332), is planned in this study. This is 
anticipated to be at the lower end of the clinically effective dose range, and below the 
anticipated Phase 2/3 dose of PF-07321332/ritonavir of 300/100 mg. Although single doses 
up to 750 mg PF-07321332 with ritonavir have been evaluated, exposure increased less than 
dose proportional within the 250 mg to 750 mg dose range evaluated. Therefore, 100 mg 
PF-07321332 is appropriate considering systemic exposures of PF-07321332 may be 
increased in the presence of renal impairment. 
When co-administered with ritonavir, doses of PF-07321332 up to 750 mg single dose and 
500 mg q12h for 10 days were generally safe and well tolerated based on preliminary data 


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form the Phase 1 study C4671001. There have been no deaths or serious adverse events or 
SUSARs reported. Based on review of preliminary (unaudited) data, all reported adverse 
events have been of mild intensity. There were no clinically meaningful findings in vital 
signs, ECG, or potential Hy’s Law cases reported during the study. 
Doses may be modified in Part 2 based on emerging safety, tolerability, and PK data.
The dose of ritonavir to be used in this study is 100 mg administered q12h. This dose is the 
typical dose of ritonavir when dosed as a PK enhancer. As ritonavir is not eliminated renally, 
and is not expected to be significantly altered by renal impairment, no dose reduction is 
considered necessary. 
4.4. End of Study Definition
The end of the study is defined as the date of last scheduled procedure shown in the SoA for 
the last participant in the trial.
A participant is considered to have completed the study if he/she has completed all parts of 
the study, including the last scheduled procedure shown in the SoA.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. 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.
5.1. Inclusion Criteria
5.1.1. All Participants
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants must be 18 to 75 years of age, inclusive, at the time of 
signing the ICD.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, and other study procedures.


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Weight:
3. BMI of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb).
Informed Consent:
4. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.1.2. Additional Inclusion Criteria for Healthy Participants with Normal Renal 
Function (Cohort 3 Only)
1. No clinically relevant abnormalities identified by a detailed medical history, full 
physical examination, including temperature, BP and pulse rate measurement, 
12-lead ECG and clinical laboratory tests.
2. Normal renal function (eGFR ≥90 mL/min) at 2 Screening visits based on the CKD-
EPI equation. 
3. Demographically comparable to the group of participants with impaired renal 
function.

Each participant’s body weight within ±15 kg of the mean body weight of renal 
impairment group.

Each participant’s age within ±10 years of the mean age of the renal impairment 
group.

Attempts will be made to ensure that the male-to-female composition of Cohort 3 
is comparable to that in the renal impairment groups; cohorts cannot be comprised 
entirely of any one gender.

Other demographic characteristics, such as race and ethnicity, matched as closely 
as possible to the renal impairment group. 
5.1.3. Additional Inclusion Criteria for Participants with Impaired Renal Function 
(Cohort 1 and Cohort 2 & Cohort 4 [If Applicable] Only)
1. Good general health commensurate with the population with chronic kidney disease 
(renal impairment). “Health” is defined as no clinically relevant abnormalities 
identified by a detailed medical history, full physical examination, measurement of 
pulse rate and 12-lead ECG as well as clinical laboratory tests (except serum 
creatinine and eGFR). Hypertension, diabetes mellitus, hyperparathyroidism, 
ischemic heart disease and other common co-morbidities in this population are 
possible exemptions, as long as, in the opinion of the investigator, the participant is 


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medically stable, is on a stable drug regimen, and can abide by the meals and dietary 
restrictions outlined in protocol Section 5.3.1.
2. Meet the following eGFR criteria during the screening period based on the CKD-EPI 
equation: 

Mild renal impairment: eGFR between 60 – <90 mL/min.

Moderate renal impairment: eGFR ≥30 mL/min and <60 mL/min.

Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis. 
The eGFR values obtained at the 2 screening visits should not be more than 
25% different (see Section 4.1).
3. Any form of renal impairment except acute nephritic syndrome (participants with 
history of previous nephritic syndrome but in remission can be included).
4. Stable concomitant drug regimen (as defined in Section 6.8) for the management of 
individual participant’s medical conditions; on a case-by-case basis, with input from 
the sponsor, participants receiving fluctuating concomitant medication/treatment may 
be considered if the underlying disease is under control
5.2. Exclusion Criteria
5.2.1. All Participants
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Positive test result for SARS-CoV-2 infection at the time of screening or Day -1.
2. History of HIV infection, hepatitis B, or hepatitis C; positive testing at screening for 
HIV, HBsAg, HBcAb, or HCVAb. As an exception a positive HBsAb test due to 
Hepatitis B vaccination is allowed.
3. Renal transplant recipients.
4. Urinary incontinence without catheterization, at investigators discretion.
5. Any condition possibly affecting drug absorption (eg, prior bariatric surgery, 
gastrectomy, cholecystectomy, appendectomy).
NOTE: participants who have undergone cholecystectomy and/or 
appendectomy are eligible for this study so long as the surgery occurred more 
than 6 months prior to Screening.


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6. Other medical or psychiatric condition including history of pancreatitis, recent 
(within the past year) or active suicidal ideation/behavior or laboratory abnormality or 
other conditions or situations related to COVID-19 pandemic (eg, Contact with 
positive case, residence, or travel to an area with high incidence) that may increase 
the risk of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
Prior/Concomitant Therapy:
7. Participants who have been vaccinated with COVID-19 vaccines within the past 
1 week of dosing, or are to be vaccinated with these vaccines at any time during 
confinement.
8. 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. 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.
For participants with renal impairment, stable concomitant medications (including 
herbal supplements) may be given following approval by the sponsor if they are 
considered necessary for the welfare of the study participants (eg, standard therapy 
for underlying diseases), are not contraindicated with the IP, and are unlikely to 
interfere with the PK of the IP. 
9. Current use of any prohibited concomitant medication(s) or those unwilling/unable to 
use a permitted concomitant medication(s). Refer to Section 6.8 Concomitant 
Therapy.
Prior/Concurrent Clinical Study Experience:
10. Previous administration with an investigational drug 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). 


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Diagnostic Assessments:
11. A positive urine drug test, for illicit drugs, at Screening: 
NOTE: repeat urine drug testing is not permitted in this study.
Renal impairment participants may be eligible to participate after approval from 
sponsor if their drug screen is positive for a prescribed substance that is not expected 
to interfere with the PK of PF-07321332. 
12. Baseline standard 12-lead ECG that demonstrates:

Clinically relevant abnormalities requiring treatment (eg, acute myocardial 
infarction, serious tachy- or brady-arrhythmias) or indicating serious underlying 
heart disease (eg, prolonged PR interval, cardiomyopathy, underlying structural 
heart disease, Wolff Parkinson–White syndrome); 

Confirmed QTcF >450 msec for participants with normal renal function and 
>470 msec for participants with impaired renal function
13. 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: 

AST or ALT level >2 × ULN;

Total bilirubin level ≥1.5 × 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.
14. In the opinion of the investigator or Pfizer (or designee), have any clinically 
significant laboratory abnormality that that could affect interpretation of study data or 
the participant’s participation in the study. 
15. Screening laboratory tests with abnormal results may be repeated once to confirm 
abnormal results (with the same screening number); the last value will be used to 
determine eligibility.
16. Sites may be permitted to re-screen participants (with a new screening number) who 
initially do not meet eligibility criteria once following agreement with the sponsor.
Other Exclusions:
17. History of regular alcohol consumption exceeding 7 drinks/week for females or 
14 drinks/week for males (1 drink = 5 ounces [150 mL] of wine or 12 ounces
[360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) or binge drinking and/or any 


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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. 
18. Female participants of childbearing potential who are unwilling or unable to use 
highly effective methods of contraception as outlined in Section 5.3.4 for the duration 
of the study and for at least 28 days after the administration of investigational 
product, pregnant female participants, female participants planning to become 
pregnant during the duration of the study until 28 days after the administration of 
investigational product, breastfeeding female participants. 
19. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing.
20. History of sensitivity to heparin or heparin -induced thrombocytopenia, only if 
heparin is used to flush intravenous catheters used during serial blood collections.
21. History of sensitivity reactions to ritonavir or any of the formulation components of 
PF-07321332 or ritonavir.
22. Unwilling or unable to comply with the criteria in Protocol Section 5.3 Lifestyle 
Considerations.
23. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family
members.
5.2.2. Additional Exclusion Criteria for Healthy Participants with Normal Renal 
Function (Cohort 3, Only)
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).
2. 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.
5.2.3. Additional Exclusion Criteria for Participants with Impaired Renal Function 
(Cohort 1, Cohort 2 and & Cohort 4 [If Applicable] Only)
1. Participants requiring hemodialysis and/or peritoneal dialysis
2. Participants with other clinically significant disease that may affect the safety of the 
participant or that may affect the PK of PF-07321332. Participants with any 


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significant hepatic, cardiac, or pulmonary disease or participants who are clinically 
nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart 
disease, etc. are not cause for exclusion as long as, in the opinion of the investigator, 
the participant is medically stable and any drugs that are administered for these 
conditions are not expected to interfere with the PK of PF-07321332. 
3. Screening BP ≥180 mm Hg (systolic) or ≥110 mm Hg (diastolic), following at least 
5 minutes of supine rest. If initial BP is ≥180 mm Hg (systolic) or ≥110 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.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. 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 and PF-07321332 administration on Day 1. There will be no restriction to 
breakfast on the other days provided other restrictions are followed.

Water is permitted until 1 hour prior to PF-07321332 administration. Water may be 
consumed without restriction beginning 1 hour after dosing. There are no water 
restrictions for dosing with ritonavir. Noncaffeinated drinks (except grapefruit or 
grapefruit-related citrus fruit juices—see below) may be consumed with meals and 
the evening snack.

Lunch will be provided approximately 4 hours after dosing.

Dinner will be provided approximately 9 to 10 hours after dosing.

An evening snack may be permitted.

Participants will refrain from consuming red wine, grapefruit, or grapefruit-related 
citrus fruits (eg, Seville oranges, pomelos) 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.
5.3.2. Caffeine, Alcohol, and Tobacco

Participants will abstain from caffeine-containing products for 24 hours prior to the 
start of dosing until collection of the final PK sample of each study period.


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Participants will additionally abstain from caffeine-containing products at least 
2 hours prior to any scheduled vital sign and ECG measurements.

Participants will abstain from alcohol for 24 hours prior or as specified above for red 
wine to admission to the CRU and continue abstaining from alcohol until collection 
of the final PK sample of each study period. Participants may undergo an alcohol 
breath test or blood alcohol test at the discretion of the investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to dosing and during confinement in the CRU. 
5.3.3. 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;

In order to standardize the conditions on PK sampling days, participants will be 
required to refrain from lying down (except when required for BP, respiratory rate, 
pulse rate, and ECG measurements), eating, and drinking beverages other than water 
during the first 4 hours after dosing of PF-07321332 (does not apply to ritonavir 
dosing).
5.3.4. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her 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 the schedule of activities (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 or if pregnancy is known or suspected in the participant or partner.
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 to the clinical database.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if prior reason for not meeting the eligibility criteria has been resolved.
Rescreening may only occur with sponsor approval. In the event that the participation of a 


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participant in the study is delayed, outdated screening procedures can be repeated.
Rescreened participants should be assigned the same participant number as for the initial 
screening.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to PF-07321332 and ritonavir.
6.1. Study Intervention(s) Administered
For this study, the investigational products are PF-07321332 (provided as 100 mg tablets)
and ritonavir (provided as 100 mg tablets).
PF-07321332 100 mg tablets and ritonavir 100 mg tablets will be supplied by Pfizer to the 
CRU in bulk along with individual dosing containers for unit dosing.
6.1.1. Administration
Investigational products will be administered orally and according to the conditions 
described in the SoA section and Protocol Section 5.3.1 Meals and Dietary Restrictions.
On Day -1, 12 hours prior to dosing of PF--07321332, participants will receive a 100 mg 
ritonavir tablet (as 1 × 100 mg) with approximately 240 mL ambient temperature water. On 
Day 1, following an overnight fast of at least 10 hours, participants will receive 100 mg 
PF-07321332 (as 1 × 100 mg tablet) at approximately 0800 hours (plus or minus 2 hours)
and 100 mg ritonavir (as 1 × 100 mg tablet). Participants will receive 2 additional doses of 
100 mg ritonavir (as 1 × 100 mg tablet) at 12 and 24 hours after receiving PF-07321332. 
Investigator site personnel will administer study intervention with ambient temperature water 
to a total volume of approximately 240 mL. Participants will swallow the study intervention
whole, and will not manipulate or chew the study intervention prior to swallowing. 
In order to standardize the conditions of PK sampling, 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 of 
PF-07321332.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions 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 or administer study intervention. All study 


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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 for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, 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 definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. The investigator, institution, or the head of the medical institution (where applicable) 
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.
7. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. 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 
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 IP manual.
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.


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PF-07321332 and ritonavir tablets 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 tablets will be provided to the participant in unit 
dose containers and labeled in accordance with Pfizer regulations and the clinical site’s 
labeling requirements. 
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
The investigator will assign participant numbers to the participants as they are screened for 
the study. All participants enrolled will receive treatment according to the dose/schedule.
6.4. Study Intervention Compliance
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.
6.5. Dose Modification
Dose modifications for PF-07321332 and ritonavir are not allowed in Part 1. The dose of 
PF-07321332 may be reduced in Part 2 for participants with severe renal disease if 
considered necessary by the investigator and sponsor to ensure participant safety.
6.6. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation.
6.7. Treatment of Overdose
For this study, any dose of PF-07321332 greater than 100 mg or ritonavir greater than 
200 mg within a 24-hour time 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 medical monitor within 24 hours.


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2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-07321332 or ritonavir 
(whichever is longer).
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 within 2 days from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis).
6.8. 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.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
For participants with renal impairment, stable concomitant medications (including herbal 
supplements) may be given following approval by the sponsor if they are considered 
necessary for the welfare of the study participants (eg, standard therapy for underlying 
diseases), are not contraindicated with the IP (see Appendix 8), and are unlikely to interfere 
with the PK of the IP.
As PF-07321332 and ritonavir are both primarily metabolized by CYP3A4, concomitant use 
of any medications or substances that are strong inducers of CYP3A4 are prohibited within 
28 days prior to dosing of investigational product. Additionally, ritonavir and PF-07321332 
are inhibitors of CYP3A4. Therefore, medications highly dependent on CYP3A4 for 
clearance and for which elevated plasma concentrations may be associated with serious 
and/or life-threatening events are not permitted during dosing of PF-07321332/ritonavir. A 
non-exhaustive list of prohibited and precautionary medications is provided in Appendix 8. If 
a medication is not listed, it should not automatically be assumed it is safe to co-administer. 
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.


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6.8.1. Participants with Healthy Renal Function (Cohort 3 Only)
In general, participants will abstain from all concomitant treatments (prescription or over the 
counter) as described in Protocol Section 6.8, except for the treatment of AEs. Of note, the 
following restrictions apply:

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 
after approval by the sponsor.
6.8.2. Participants with Impaired Renal Function (Cohort 1, and Cohorts 2 & 4 [If 
Applicable])
Participants are permitted to be on stable doses of background medications if they are 
considered necessary for the welfare of the study participants (eg, standard therapy for the 
underlying disease), are not contraindicated with the investigational product, and are unlikely 
to interfere with the PK of the investigational product. Whenever possible, attempts must be 
made to not alter the doses and regimens of the concomitant medications after Day 1 and 
until the end of study on Day 3.

Approved concomitant medications should be administered to renally impaired 
participants at least 2 hours prior to dosing or withheld until 4 hours after 
PF-07321332 dosing.
6.8.3. Rescue Medicine 
There is no rescue therapy to reverse the AEs observed with PF-07321332 or ritonavir; 
standard medical supportive care must be provided to manage the AEs. 
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;

Positive COVID-19 test.
Note that discontinuation of study intervention does not represent withdrawal from the study.
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for safety and PK, if possible. See the SoA for data to be collected at the time of 
discontinuation of study intervention and follow-up for any further evaluations that need to 
be completed.


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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, posttreatment study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;
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.
If a participant withdraws from the study, he/she 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 should be performed and no 
additional data should 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 him or her 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 


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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 he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND 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.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
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 


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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, eg, banked biospecimens, may 
be used without repeat collection, 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 
circumstances outside the control of the investigator that may 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 he or she has 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 in this study is approximately 
105 mL. The actual collection times 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 60 consecutive 
days.
To prepare for study participation, participants will be instructed on the information in 
Protocol Section 5.3 Lifestyle Considerations and Section 6.8 Concomitant Therapy.
8.1. Efficacy Assessments
Not applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in 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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8.2.1. 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, and participant-reported symptoms.
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 data 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 8.3.1 to Section 8.3.3.
8.2.2. Vital Signs
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. Participants should be 
instructed not to speak during measurements. 
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.
8.2.2.1. Respiratory Rate 
Respiratory rate will be measured after approximately 5 minutes of rest in a supine position 
by observing and counting the respirations of the participant for 30 seconds and multiplying 
by 2. When BP is to be taken at the same time, respiration measurement will be done during 
the 5 minutes of rest and before BP measurement.


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8.2.2.2. Temperature
Temperature will be measured orally other body locations, eg tympanic, are acceptable 
provided the same method is used and documented throughout the study). No eating, 
drinking, or smoking is allowed for 15 minutes prior to the measurement.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) 
should not be used given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement. 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 ≥30 msec from the baseline and is >450 msec for 
participants with normal renal function and >470 msec for participants with impaired renal 
function; or b) an absolute QT value is ≥500 msec 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 QTc 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 ≥30 msec from the baseline and is >450 msec for 
participants with normal renal function and >470 msec for participants with impaired renal 
function; or b) an absolute QT value is ≥500 msec for any scheduled ECG for greater than 
4 hours (or sooner, at the discretion of the investigator); or c) QTcF intervals get 
progressively longer, the participant should undergo continuous ECG monitoring. 
A cardiologist should be consulted if QTcF intervals 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.


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8.2.4. 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.
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.
Clinically significant abnormal laboratory findings are those which 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 significantly abnormal during 
participation in the study or within 28 calendar days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor.
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 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
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. 
8.2.5. COVID-19 Specific Assessments 
Participants will be tested for SARS-COVID-19 infection by RT-PCR prior to being 
admitted to the clinic for confinement and a subsequent COVID-19 test will be performed if 
they develop COVID-19 like symptoms. Additional testing may be required by local 
regulations or by the Principal Investigator.
8.2.6. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but 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 the participant’s receiving the study intervention. Pregnancy tests will also be done 


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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.
8.3. 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 8.3.1, each participant 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.
8.3.1. 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 the participant’s participation in the study (ie, 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 and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator.
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.


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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.
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 completed the study, and he/she 
considers 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.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 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 it being available.
8.3.1.2. 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 8.3.1, 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.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
8.3.2. 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.
8.3.3. 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 


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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 given in Appendix 3.
8.3.4. 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.
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.
8.3.5. 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 exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.3.5.1. 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 exposes a 
female partner prior to or around the time of conception.


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
A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to 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.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion then exposes 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 a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after
the last dose.

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 CT SAE Report Form 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 EDP Supplemental Form. 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 
preprocedure 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;


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
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.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by ingestion.
The investigator must report exposure during breastfeeding 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 exposure during 
breastfeeding 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 CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. 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 CT SAE Report Form must be maintained in the 
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8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. 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.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
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.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.


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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Pharmacokinetics 
8.4.1. Plasma for Analysis of PF-07321332 
Blood samples of approximately 4 mL, to provide a minimum of 1.5 mL, will be collected 
for measurement of plasma concentrations of PF-07321332 as 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 data collection tool (eg, CRF/DCT). 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 data collection tool 
(eg, CRF/DCT). 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 PF-07321332. Each plasma sample will be 
divided into 2 aliquots. Samples collected for analyses of PF-07321332 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, 
 
 
Samples may be used to evaluate the PK of ritonavir.
Samples collected for measurement of plasma concentrations of PF-07321332 will be 
analyzed using a validated analytical method in compliance with applicable SOPs.
 
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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.
8.4.2. Urine for Analysis of PF-07321332
Urine will be collected at the intervals outlined in the SoA. Each participant will empty 
his/her bladder just prior to dosing. During the subsequent designated urine collection 
intervals ([0-24], and [24-48] hours post dose), participants will void ALL urine produced 
during the designated collection interval, including a forced void at the end of the collection 
interval, directly into pre-weighed urine collection container. Each collection interval should 
have its own collection container(s). During the entire collection interval, the container(s) 
should be stored at 4°C. At the end of each urine collection interval, all urine collected will 
be thoroughly mixed, total weight of urine will be determined first (weigh the empty 
container first and then weigh the container at the end of the collection) and then the volume 
of urine will be calculated by assuming specific gravity of urine = 1 and recorded on the 
CRF. A urine aliquot of 4 mL will be withdrawn for measurement of drug concentrations.
Additional details for collection, processing and storage of urine for analysis of PF-07321332
will be added to the laboratory manual and provided to the investigator site prior to the start 
of the study.
Urine samples will be analyzed for PF-07321332 using a validated analytical method in 
compliance with Pfizer SOPs, if it is determined by the study team that there is a need to do 
so, based on review of plasma PK results for PF-07321332. Specifically if the estimate of the 
ratio of PF-07321332 AUCinf for the moderate renal impairment group compared to healthy 
normals is <1.5, urine samples will be analyzed.  
Urine samples may be used to evaluate the PK of ritonavir or metabolite identification and/or 
evaluation of the bioanalytical method, 
 
 
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8.7. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.8. 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 a 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
No statistical hypothesis will be tested in this study.
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis 
Set
Description
PK Concentration
The PK concentration population is defined as all participants 
assigned to investigational product and treated who have at 
least 1 concentration measured.
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Participant Analysis 
Set
Description
PK Parameter
The PK parameter analysis population is defined as all 
participants assigned to investigational product and treated 
who have at least 1 of the PK parameters of primary interest 
measured.
Safety Analysis Set
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Participants 
will be analyzed according to the product they actually 
received.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed 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.
ANOVA will be used to compare the natural log transformed AUCinf (or AUClast if AUCinf
cannot be reliably estimated) and Cmax for PF-07321332 between normal renal function group 
(Reference) and each impaired renal function group separately as applicable (Test). Estimates 
of the adjusted mean differences (Test-Reference) and corresponding 90% CIs will be
obtained from the model. The adjusted mean differences and 90% CIs for the differences will 
be exponentiated to provide estimates of the ratio of the adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. If substantial differences in demographic 
characteristics between healthy and impaired participants are observed, weight and age may 
be explored as covariates.
Box and whisker plots for individual participant parameters (AUCinf and Cmax) will be
constructed by renal function group and overlaid with geometric means.
For summary statistics and median/mean plots by sampling time, the nominal PK sampling 
time will be used. For individual participant plots by time, the actual PK sampling time will 
be used.
Linear regression will be used to analyze the potential relationship between appropriate PK
parameters (CL/F or CLr, and Vz/F) and renal function (eGFR). Estimates of the slope and, 
intercept, together with their precision (90% CI), and the coefficient of determination will be 
obtained from the model.
Plots of PK parameters (CL/F or CLr, and Vz/F) versus renal function (eGFR) will be 
constructed. A regression line and 90% confidence region for the PK parameters and eGFR 
will be included if appropriate. Vertical lines for the renal function group cut-off values will 
also be presented on the plots. Different symbols will be used to identify participants from 
different renal function groups.


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9.3.1. Other Safety Analyses
All safety analyses will be performed on the safety population.
AEs, ECGs, BP, pulse rate, 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, BP, and pulse rate 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 and neurological examination information, as 
applicable, 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 and/or neurological 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. Pharmacokinetic Analyses
9.3.2.1.1. Analysis Population
The PK concentration population will be defined as all participants treated in whom at least 
1 plasma concentration value is reported.
The PK parameter analysis population is defined as all participants dosed who have at least 
1 of the PK parameters of primary interest.
9.3.2.1.2. Derivation of Pharmacokinetic Parameters Prior to Analysis
The plasma PK parameters for PF-07321332 will be derived from the concentration time 
profiles as detailed in Table 3. 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 
time will be used in the derivation of PK parameters.
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Table 3.
Plasma PK Parameters
Parameter
Analyte
Definition
Method of Determination
AUClast
PF-07321332
Area under the plasma 
concentration-time profile from 
time 0 to the time of Clast
Linear/Log trapezoidal method.
AUCinf*
PF-07321332
Area under the plasma 
concentration-time profile from 
time 0 extrapolated to infinite 
time
AUClast + (Clast*/kel), Where Clast* is 
the predicted plasma concentration 
at the last quantifiable time point 
estimated from the log-linear 
regression analysis.
Cmax
PF-07321332
Maximum plasma concentration
Observed directly from data.
Tmax
PF-07321332
Time for Cmax
Observed directly from data as time 
of first occurrence.
C12
PF-07321332
Concentration at 12h
Observed directly from data.
C24
PF-07321332
Concentration at 24h
Observed directly from data.
t½*
PF-07321332
Terminal elimination 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. Only 
those data points judged to describe 
the terminal log-linear decline will 
be used in the regression.
CL/F*
PF-07321332
Apparent clearance
Calculated as AUCinf/Dose.
Vz/F*
PF-07321332
Apparent volume of distribution
Calculated as Dose/(AUCinf×kel).
*
As data permit.
If urine samples need to be analyzed (See Section 8.4.2), the following urine PK parameters 
(Table 4) will be calculated for PF-07321332 (as data permit):
Table 4.
Urine PK Parameters
Parameter
Analyte
Definition
Method of Determination
Ae48
PF-07321332
Total amount of unchanged drug 
excreted in the urine over 48 hours
Sum of amount excreted for each 
collection period.
Ae48% 
PF-07321332
Total amount of unchanged drug 
excreted in the urine over 48 hours, 
expressed as percent of dose
100×(Ae48/Dose)
CLr
PF-07321332
Renal clearance
Ae48/AUC48
Urine PK parameters will be analyzed and summarized using descriptive statistics.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is an open-label study,
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical 
development. 


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9.5. Sample Size Determination
In Part 1, approximately 8 participants will be enrolled into the normal renal function group 
and approximately 8 participants into each of the mild and moderate renal impairment 
groups, to ensure approximately 6 evaluable completers in each group. In Part 2, 
approximately 8 participants will be enrolled to the severe renal groups to ensure 
approximately 6 evaluable completers per group. Additional participants may be enrolled 
into the normal renal function group to ensure adequate matching; however the total number 
will not exceed 12. The sample size is based on recommendations from the “FDA Guidance 
for Industry - Pharmacokinetics in Patients with Impaired Renal Function-Study Design, 
Data Analysis, and Impact on Dosing and Labeling”.6
Participants who discontinue from the study before completing all assessments may be 
replaced at the discretion of the investigator and sponsor.


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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 (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), 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 subinvestigators 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 his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant 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 study 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 his/her 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 his/her 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 his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her 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.


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Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened are required to sign a new ICD.
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 form and 
will be password-protected 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 his or her 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.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will not use a 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, and/or 
www.pfizer.com, and other public registries 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.
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.


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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
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data sharing
Pfizer provides researchers secure access to patient-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 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
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.


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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 
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 form and are password-protected 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 data 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 


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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.
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.
Definition of what constitutes source data and its origin can be found in clinical monitoring 
plan, 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 data) that supports the 
information entered in the CRF.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
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. 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 designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.


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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.
10.1.10. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications,
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor 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- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 


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If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.11. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the SToD system.
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, 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 investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she 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. 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 Safety 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 and creatininea
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Creatine kinase
TSH and free T4
Local Dipstick:
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Laboratory:
Microscopyb
•
SARS-CoV-2 RT-PCR
•
aPTT
•
PT-INR
•
Fibrinogen
•
FSHc
•
Urine drug screeningd
•
Breath or urine alcohol 
teste
•
Pregnancy test (β-hCG)f
•
HIV
•
HbsAg
•
HbcAb
•
HCVAb 
•
Urine myoglobing
a.
Only serum creatinine will be assessed at S2 for eGFR assessment.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
c.
At S1 for confirmation of postmenopausal status only.
d.
At S1 and Day -1; The minimum requirement for drug screening includes cocaine, THC, 
opiates/opioids, benzodiazepines, and amphetamines (others are site and study specific).
e.
Complete at S1 and Day -1.
f.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/EC. Serum or urine β-hCG for female participants of childbearing potential.
g.
Reflex testing for creatine kinase >10 × ULN.
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.
Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained and 
stored for the duration of the study.
 
These data will not be included in the CSR. Samples to be used for this 
purpose will be shipped to either a Pfizer-approved BBS facility or other designated 
laboratory and retained for up to 1 year following the completion of the study.
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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 laboratory 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 either 
an increase in 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, is considered serious.
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 on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 


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It should be noted that the CT 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 for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT 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 exposure during 
pregnancy or breastfeeding
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 non-
participant (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 AE or SAE): any pregnancy information 
is reported to Pfizer Safety using CT SAE Report Form and EDP 
Supplemental Form; if the EDP is associated with an SAE, then the SAE is 
reported to Pfizer Safety using the CT SAE Report 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.


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
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.

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.

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: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc.

Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self care ADL. Self care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden.
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.


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If required on the AE page of the CRF, the investigator will use the adjectives 
MILD, MODERATE, SEVERE, or VERY SEVERE to describe the maximum 
intensity of the AE. The severity of the AE should be determined using the Toxicity 
Grading Scale: 
MILD
Does not interfere with participant's usual function.
MODERATE
Interferes to some extent with participant's usual function.
SEVERE
Interferes significantly with participant's usual function.
VERY SEVERE
Unacceptable and intolerable events or events which are 
irreversible or cause the participant to be in imminent danger of 
death.
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.

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 his/her assessment.

For each AE or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or SAE and has 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.


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
The investigator may change his/her 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.

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 Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data
become available.


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
After the study is completed at a given site, the electronic data collection tool 
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 data collection 
tool 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 CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, 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 with a female of childbearing potential 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 woman of childbearing 
potential 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
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 definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below
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). The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.


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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 in adolescents or athletes) 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 an alternate 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 nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.


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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.
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 (eg, bilateral tubal ligation).
5. Vasectomized partner.

A 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;

Intravaginal;

Transdermal;

Injectable.
7. Progestogen--only hormone contraception associated with inhibition of ovulation.

Oral;

Injectable.
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 


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evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent:

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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10.6. Appendix 6: 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.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within 
the same laboratory sample). In rare instances, by the time TBili 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 TBili 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 TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili 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 TBili 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).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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Rises in AST/ALT and TBili 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 TBili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, 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, 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 
TBili 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.


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 87
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 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec 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 seconds’
duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia.

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 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 pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 88

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm 
(heart rate <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 enumerated list of major events of potential clinical concern 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 to be reported as AEs/SAEs.


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 89
10.8. Appendix 8: Prohibited and Precautionary Concomitant Medications That May 
Result in DDI
The prohibited concomitant medications listed below should not be taken with PF-07321332 
and ritonavir during dosing and up to 4 days after the final dose of ritonavir.
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
This list of drugs prohibited or precautionary 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).
This is not an all-inclusive list. Site staff should consult with the sponsor or designee with 
any questions regarding potential DDI.
Prohibited Medications
Medications that are Strong Inducers of CYP3A4a
Drug Class
Specific Medication
Clinical Comments
Anti-infectives
Rifampin
Potential to impact the PK of 
PF-07321332 and ritonavir
Anti-epileptic
Phenytoin, carbamazepine
Herbal Products
St. John's wort
Medications Dependent on CYP3A4 for Clearance, with Drug Interactions with
PF-07321332/ritonavira
Alpha 1-Adrenoreceptor 
Antagonist
Alfuzosin
Risk of hypotension, syncope
Antianginal
Ranolazine
Risk of cardiac arrhythmias 
Antiarrhythmics 
Amiodarone, Bepridil, Flecainide, 
Propafenone, Quinidine, 
Dronedarone, Encainide
Risk of cardiac arrhythmias 
Anti-gout
Colchicine
Potential for serious and/or life-
threatening reactions in patients with 
renal and/or hepatic impairment
Antihistamines
Astemizole, Terfenadine
Risk of cardiac arrhythmias
Antipsychotics
Lurasidone
Potential for serious and/or life-
threatening reactions
Ergot Derivatives
Dihydroergotamine, Ergonovine, 
Ergotamine, Methylergonovine
Risk of acute ergot toxicity 
(peripheral vasospasm and ischemia 
of the extremities)
HMG CoA Reductase 
Inhibitors 
Lovastatin, Simvastatin 
Risk of rhabdomyolysis; consider 
alternative agent: pravastatin
Neuroleptic
Pimozide
Risk of cardiac arrhythmias 
PDE-5 inhibitors
Sildenafil (Revatio) - PAH
Risk of visual disturbances, 
hypotension, prolonged erection, and 
syncope
Sedatives/hypnotics
Oral Midazolam, Triazolam
Risk of prolonged sedation or 
respiratory depression
a.
If a drug is not listed, it should not automatically be assumed it is safe to co-administer.


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 90
Precautionary Medications
Medications to be Used with Caution when Co-administered with PF-07321332/ritonavira
Drug Class 
Specific Drugs 
Clinical Comments 
Anesthetic
Meperidine
Dosage increase and long-term use of 
meperidine with ritonavir are not 
recommended due to the increased 
concentrations of the metabolite
normeperidine which has both analgesic 
activity and CNS stimulant activity (eg, 
seizures).
Antiarrhythmics
Disopyramide, Lidocaine, Mexiletine
Caution is warranted and therapeutic 
concentration monitoring is 
recommended for antiarrhythmics when
co-administered with ritonavir, if 
available.
Anticancer Agents
Dasatinibm, Nilotinibm, Vincristine, 
Vinblastine
Potential increase in anticancer agent.
Anticonvulsants
Lamotrigine, 
Valproate
Phenytoin
Divalproex
Carbamazepine
Co-administration may decrease 
lamotrigine, valproate, divalproex, and 
phenytoin concentrations. 
Co-administration may increase 
carbamazepine concentrations. Careful 
monitoring of adverse effects.
Alternative agents: Gabapentin 
Topiramate
Anticoagulants
Rivaroxaban
Warfarin
Increased risk of bleeding; consider 
alternative anticoagulant.
Co-administration may increase or 
decrease warfarin levels. Frequent 
monitoring of INR during 
co-administration is recommended
Antidepressant
Trazadone, Desipramine, Fluoxetine 
Paroxetine, Sertraline, Nefazadone, 
Amitriptyline, Nortriptyline
Bupropion
May increase antidepressant 
concentration.
Co-administration may decrease 
bupropion concentration. 
Antiemetic
Dronabinol
Co-administration may increase 
dronabinol concentrations; a dose 
reduction of dronabinol may be needed.
Anti-infective
Clarithromycin
Co-administration may increase 
clarithromycin concentration. 
Antifungals
Itraconazole, Ketoconoazole
Voriconazole
Co-administration may increase 
itraconazole, ketoconazole
concentration. Monitor for adverse 
effects.
Co-administration may decrease 
voriconazole concentration.


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 91
Precautionary Medications
Medications to be Used with Caution when Co-administered with PF-07321332/ritonavira
Antimycobacterial
Bedaquiline, Rifabutin
Co-administration may increase 
bedaquiline, rifabutin concentrations.
Antiparasitic
Atovaquone
Quinine
Co-administration may decrease 
atovaquone concentrations.
Co-administration may increase quinine
Antipsychotic
Perphenazine, Risperidone, 
Thioridazine, Quetiapine
Co-administration may increase 
antipsychotic concentrations. 
Beta Blockers
Metoprolol, Timolol
Co-administration may increase beta-
blocker concentration. A dose decrease 
may be needed for these drugs when 
co-administered with ritonavir.
Bronchodilator
Theophylline
Increased dose of theophylline may be 
required. 
Calcium Channel 
Blockers 
Diltiazem, Verapamil, Felodipine, 
Nicardipine, Nisoldipine, Nifedipine, 
Amlodipine
Co-administration may increase 
concentrations. The impact on the PR 
interval of co-administration of ritonavir 
with other drugs that prolong the PR 
interval (including calcium channel 
blockers) has not been evaluated. If 
co-administration is indicated, consider a 
dose reduction (amlodipine 
recommended dose reduction of 50%). 
Close monitoring is recommended.
Cardiac Glycosides
Digoxin
Co-administration increases digoxin 
concentration.
Contraceptives
Hormonal contraception
Recommend barrier method
Endothelin Receptor 
Antagonist
Bosentan
Co-administration may increase 
bosentan concentrations.
Hepatitis C direct 
acting antivirals
Boceprevir, Glecaprevir/Pibrentasvir
Simeprevir, 
Sofosbuvir/Velpatasvir/Voxilaprevir
Ombitasvir/Paritaprevir/Ritonavir, 
Dasabuvir
Co-administration is not recommended 
as it resulted in increased plasma 
concentrations of Hep C antiviral; 
Caution or not recommended.
HIV Protease 
Inhibitors
NNRTs, Fusion 
Inhibitors
Lopinavir, Amprenavir, Indinavir, 
Nelfinavir, Saquinavir, Atazanavir,
Abacavir, Didanosine, Darunavir, 
Tipranavir, Zidovudine
Co-administration may increase HIV 
protease inhibitor concentrations; 
co-administer with caution.
HIV-1 CCR5 
antagonist
Maraviroc
See prescribing information for 
maraviroc for details on 
co-administration of maraviroc and 
ritonavir-containing proteases inhibitors.
HMG CoA reductase 
inhibitors
Atorvastatin, Rosuvastatin
Use with caution; risk of myopathy 
including rhabdomyolysis. Use lowest 
dose of statin.
Alternative agents: Pravastatin.
Hypoglycemics
Glipizide, Tolbutamide
Repaglinide
Potentially decrease glipizide and 
tolbutamide concentrations. 
Potentially increase repaglinide 
concentrations. 


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 92
Precautionary Medications
Medications to be Used with Caution when Co-administered with PF-07321332/ritonavira
Immunosuppressants
Cyclosporine, Tacrolimus, Sirolimus
Co-administration may increase 
immunosuppressant concentrations. 
Integrase Inhibitor
Raltegravir
The effects of ritonavir on raltegravir 
with ritonavir dosage regimens greater 
than 100 mg twice daily have not been 
evaluated, however raltegravir
concentrations may be decreased with 
ritonavir co-administration.
Narcotic Analgesics
Methadone, Fentanyl, Tramadol, 
Propoxyphene
Moderate to weak decreases in 
methadone AUC have been observed.
Fentanyl concentration may increase.
Analgesic concentrations may increase 
and a dose decrease may be needed for 
these drugs when co-administered.
PDE-5 Inhibitors
Avanafil, Sildenafil, Tadalafil, 
Vardenafil
Increased concentrations of PDE-5 
inhibitors.
Sedative/Hypnotic
Buspirone, Clorazepate, Diazepam, 
Estazolam, Flurazepam, Zolpidem, 
Midazolam
Increased concentrations of 
sedative/hypnotic.
Steroids
Budesonide, Dexamethasone, 
Prednisone, Fluticasone, Budenoside, 
Increased concentration of steroid. 
Stimulant 
Methamphetamine
Increased methamphetamine 
concentrations. Use with caution. 
a.
If a drug is not listed, it should not automatically be assumed it is safe to co-administer.


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 93
10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term

ongoing/continuous event
3CLpro
3C-like protein
Ab
antibody
Abs
absolute
ADL
activities of daily living
Ae
amount of unchanged drug excreted in urine
Ae48
total amount of unchanged drug excreted in the urine over 
48 hours
Ae48%
total amount of unchanged drug excreted in the urine over 
48 hours, expressed as percent of dose
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUCinf
area under the plasma concentration-time curve from time 0 
extrapolated to infinity
AUClast
area under the plasma concentration time curve from time 0 to the 
time of the last measurable concentration
AV
atrioventricular
β-hCG
beta-human chorionic gonadotropin
BBS
Biospecimen Banking System
BID
twice a day
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BSA
body surface area
BUN
blood urea nitrogen
C-G
Cockcroft-Gault
C12
plasma concentration at 12 hours post dose 
C24
plasma concentration at 24 hours post dose 
CCR5
C-C chemokine receptor type 5
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD
chronic kidney disease
CKD-EPI 
Chronic Kidney Disease-Epidemiology Collaboration


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 94
Abbreviation
Term
CL
total clearance of drug from eg, plasma
CL/F
apparent clearance of drug from eg, plasma
Clast
last observed (quantifiable) plasma concentration
CLr
renal clearance of drug from eg plasma
Cmax
maximum observed plasma concentration
CNS
central nervous system
CO2
carbon dioxide (bicarbonate)
COVID-19
coronavirus disease 2019
CLCR
renal clearance of creatinine from serum 
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
clinical trial
CYP
cytochrome P450 
CYP3A4
cytochrome P450 3A4 
DC
discontinuation
DCT
data collection tool
DDI
drug-drug interaction 
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
DSUR
Development Safety Update Report
EC
ethics committee
ECC
Emergency Contact Card
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
EDR
extemporaneous dispensing record
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
fm
fraction metabolized
FSH
follicle stimulating hormone
fu
fraction unbound
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
CCI


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Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 95
Abbreviation
Term
GLP
Good Laboratory Practice
h
hour
HBcAb 
hepatitis B core antibody
HBsAg 
hepatitis B surface antigen
HCoV-OC43
human coronavirus OC43
HCoV-229E
human coronavirus 229E
HCoV-HKU1
human coronavirus HKU1
HCoV-NL63
human coronavirus NL63
HCVAb
hepatitis C antibody
HCV
hepatitis C virus
hep C
hepatitis C
HIV
human immunodeficiency virus
HMG CoA reductase
3-hydroxy-3-methyl-glutaryl-CoA reductase
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator's Brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IMP
investigational medicinal product
IND
Investigational New Drug 
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
ISO
International Organization for Standardization
IV
intravenous
KDOQI
Kidney Disease Outcomes Quality Initiative 
kel
terminal phase rate constant calculated by a linear regression of 
the log-linear concentration-time curve.
Ki 
inhibition constant
LFT
liver function test
MAD
multiple ascending dose
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MERS
Middle East respiratory syndrome 
msec
millisecond
mg
milligram
mL
milliliter
N/A
not applicable


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 96
Abbreviation
Term
NHP
non-human primate
NNRT
non-nucleoside reverse transcriptase 
NOAEL
no observed adverse effect level
PACL
Protocol Administrative Change Letter
PAH
pulmonary arterial hypertension
PCR
polymerase chain reaction
PD
pharmacodynamic(s)
PDE-5
phosphodiesterase type 5
pH
potential of hydrogen
PK
pharmacokinetic(s)
PT
prothrombin time
PT-INR
prothrombin time-international normalized ratio
PVC
premature ventricular contraction/complex
q12h
every 12 hours
QT
time from the beginning of the QRS complex to the end of the 
T wave
QTc
corrected QT interval
QTcF
corrected QT (Fridericia method)
qual
qualitative
RBC
red blood cell
RNA
ribonucleic acid
RT-PCR
reverse-transcriptase polymerase chain reaction
S1
Screening Visit 1
S2
Screening Visit 2
SAD
single ascending dose
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCr
serum creatinine
Scr, std
serum creatinine measured with a standardized assay for serum 
creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single-reference safety document
SToD 
Study Team on Demand
SUSAR
suspected unexpected serious adverse reaction
t½
terminal half-life
T4
thyroxine
TBili 
total bilirubin
TEAE
treatment emergent adverse event
THC
tetrahydrocannabinol
Tmax
time to first occurrence of Cmax


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 97
Abbreviation
Term
TSH
thyroid stimulating hormone
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
Vz/F
apparent volume of distribution
WBC
white blood cell
WHO
World Health Organization
WOCBP
woman/women of childbearing potential


PF-07321332
Protocol C4671011
Final Protocol Amendment 2, 08 July 2021 
PFIZER CONFIDENTIAL
Page 98
11. REFERENCES
1
WHO Situation Report 51. 11 March 2020. Available from: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. 
Accessed: 29 March 2020.
2
Anand K, Ziebuhr J, Wadhwani P, et al. Coronavirus main proteinase (3CLpro) structure: 
basis for design of anti-SARS drugs. Science. 2003;300:1763-7.
3
Investigator’s Brochure, (PF-07321332). June 2021.
4
Ritonavir [package insert]. North Chicago, IL: AbbVie Inc; 2017. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209512lbl.pdf. Accessed: 
24 June 2021.
5
Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for 
chronic kidney disease: evaluation, classification, and stratification. Annals of internal 
medicine. 2003;139(2):137-47.
6
Guidance for industry: pharmacokinetics in patients with impaired renal function—study 
design, data analysis, and impact on dosing and labeling. US FDA. Available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/pharmacokinetics-patients-impaired-renal-function-study-design-data-
analysis-and-impact-dosing-and. Accessed: 03 May 2021.

SAP_001.pdf: 
Protocol C4671011 (PF-07321332) Statistical Analysis Plan
Page 1 of 19
PFIZER CONFIDENTIAL
Protocol C4671011
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE 
PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-07321332 
BOOSTED WITH RITONAVIR IN ADULT PARTICIPANTS WITH RENAL 
IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL 
RENAL FUNCTION
Statistical Analysis Plan 
(SAP)
Version:
1.0
SAP Author: 
                       (FSP Statistician –
)
Date:
01-June-2021
PPD
PPD


Protocol C4671011 (PF-07321332) Statistical Analysis Plan
Page 2 of 19
PFIZER CONFIDENTIAL
Revision History
Version
Date
Author(s)
Summary of Changes/Comments
1.0
June 01, 2021
Not Applicable
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
PPD


Protocol C4671011 (PF-07321332) Statistical Analysis Plan
Page 3 of 19
PFIZER CONFIDENTIAL
TABLE OF CONTENTS 
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Design .............................................................................................................5
2.2. Study Objectives .......................................................................................................9
2.2.1. Primary Objectives .......................................................................................9
2.2.2. Secondary Objectives .................................................................................10
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING................................10
4. HYPOTHESES AND DECISION RULES.........................................................................10
4.1. Statistical Hypotheses .............................................................................................10
4.2. Statistical Decision Rules........................................................................................10
5. ANALYSIS SETS ...............................................................................................................10
5.1. Pharmacokinetic (PK) Analysis Set ........................................................................10
5.1.1. Concentration Analysis Set.........................................................................10
5.1.2. Parameter Analysis Set...............................................................................10
5.2. Pharmacodynamic Analysis Set..............................................................................10
5.3. Safety Analysis Set..................................................................................................11
5.4. Other Analysis Sets .................................................................................................11
5.5. Treatment Misallocations........................................................................................11
5.6. Protocol Deviations.................................................................................................11
5.6.1. Deviations Assessed Prior to Randomization.............................................11
5.6.2. Deviations Assessed Post-Randomization..................................................11
6. ENDPOINTS AND COVARIATES ...................................................................................11
6.1. Efficacy Endpoint(s) ...............................................................................................11
6.2. Safety Endpoints .....................................................................................................11
6.3. Other Endpoints.......................................................................................................12
6.3.1. PK Endpoints..............................................................................................12
6.3.2. PD Endpoints..............................................................................................13
6.4. Covariates................................................................................................................13
7. HANDLING OF MISSING VALUES ................................................................................13


Protocol C4671011 (PF-07321332) Statistical Analysis Plan
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PFIZER CONFIDENTIAL
7.1. Concentrations Below the Limit of Quantification.................................................13
7.2. Deviations, Missing Concentrations and Anomalous Values .................................13
7.3. Pharmacokinetic Parameters ...................................................................................13
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................14
8.1. Statistical Methods ..................................................................................................14
8.2. Statistical Analyses .................................................................................................14
8.3. Safety Analysis........................................................................................................16
8.3.1. Treatment and Disposition of Participants .................................................16
8.3.2. Demographic and Clinical Examination Data............................................16
8.3.3. Discontinuation(s).......................................................................................16
8.3.4. Adverse Events ...........................................................................................16
8.3.5. Laboratory Data..........................................................................................16
8.3.6. Vital Signs Data..........................................................................................16
8.3.7. ECG Data....................................................................................................17
8.3.8. Other Safety Data .......................................................................................17
8.3.9. Concomitant Treatments.............................................................................17
8.3.10. Screening and Other Special Purpose Data ..............................................17
9. REFERENCES ....................................................................................................................18
10. APPENDICES ...................................................................................................................19
LIST OF TABLES
Table 1.
Renal Function Categories by eGFR Ranges .............................................5
Table 2.
Criteria to Establish Stable Renal Function................................................9
Table 3.
Noncompartmental PK Parameters...........................................................12
Table 4.
Urine PK Parameters ................................................................................13
Table 5.
PK Parameters to be Summarized Descriptively by Cohort.....................15
LIST OF FIGURES
None.
APPENDICES
Appendix 1. SAS CODE FOR ANALYSES...........................................................................19
CCI


Protocol C4671011 (PF-07321332) Statistical Analysis Plan
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PFIZER CONFIDENTIAL
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
PF-07321332 is a potent and selective inhibitor of the SARS-CoV-2 3CL protease that is 
currently being developed as an oral treatment of COVID-19. Ritonavir is a strong CYP3A4 
inhibitor being used to inhibit the metabolism of PF-07321332 in order to increase plasma 
concentrations of PF-07321332 to values that are anticipated to be efficacious. 
The purpose of this study is to characterize the effect of renal impairment on the plasma PK 
of PF-07321332/ritonavir. Findings from this study will be used to develop dosing 
recommendations so that the dose and/or dosing interval may be adjusted appropriately in 
the presence of renal disease.
2.1. Study Design
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal 
impairment on the plasma and urine (if applicable) PK, safety and tolerability of a single 
oral dose of PF-07321332 in combination with the PK boosting agent ritonavir in 
approximately 32 participants. Part 1 will be conducted in approximately 24 adult male and 
female participants with stable mild or moderate renal impairment and a control group of 
participants with normal renal function. Part 2 will be conducted in approximately 8 adult 
male and female participants with stable severe renal impairment. A staged approach, as 
outlined in detail below, will be followed in the study.
Participants will be selected and categorized into normal renal function or renal impairment 
groups based on their eGFR as shown in table below:
Table 1.
Renal Function Categories by eGFR Ranges
Cohort
Renal Impairmenta
Estimated eGFRb(mL/min)
Number of 
Participants
1
Moderate Renal Impairment
≥30 to <60
8
2
Mild Renal Impairment
60 – 89
8
3
None (Normal))
≥90
8
4
Severe Renal Impairment
<30 and not requiring dialysis
8
a.
Stages of renal impairment are based on Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical 
Practice Guidelines for Chronic Kidney Disease (CKD).
b.
Estimate of eGFR based on CKD-EPI formula. The average of the 2 screening eGFR value will be used for 
group assignment.


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Part 1: Approximately 24 participants will be enrolled in Part 1; approximately
8 participants with moderate renal impairment (Cohort 1), approximately 8 with mild renal 
impairment (Cohort 2), and approximately 8 with normal renal function (Cohort 3), to 
ensure at least 6 evaluable participants in each group. Participants from the moderate renal 
impairment group (Cohort 1) will be recruited first. Enrollment into the mild renal 
impairment group (Cohort 2) will initiate, if necessary, after preliminary analysis of PK and 
safety data from at least 2 participants with moderate renal impairment have been reviewed.
The healthy participants (Cohort 3) will be recruited later such that each participant’s age is
within ±10 years and weight is within ±15 kg of the mean of the groups of participants with 
renal impairment group. Care will be taken when recruiting the healthy participants such 
that the entire group is not of substantially different age or of substantially different body 
weight than the moderate renally impaired participants. Approval from the sponsor must be 
obtained before proceeding with dosing healthy participants with normal renal function.
Participants with stable mild and moderate renal impairment and control participants with 
normal renal function will receive a single 100 mg dose of PF-07321332 administered orally 
in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 
12, and 24 hours relative to PF-07321332 dosing.
If there are participants who withdraw or discontinue treatment from the normal or mild or 
moderate renal impairment groups and who are considered to be non-evaluable with respect 
to the primary PK objective, additional participants can be enrolled at the discretion of the 
sponsor.
Part 2: The decision to conduct Part 2 will be made based on results from Part 1.
Enrollment into Part 2 will not commence until preliminary analysis of PK and safety data 
from at least 2 participants with moderate renal impairment have been reviewed.
Approximately 8 participants with severe (Cohort 4) renal impairment will be enrolled to 
ensure at least 6 evaluable participants in each group. As in Part 1, renal impairment 
classification will be based on eGFR. Participants will receive a single 100 mg dose of 
PF-07321332 administered orally in combination with the PK boosting agent ritonavir
administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing.
For both Parts 1 and 2: All participants in both normal and renal impairment groups will 
provide informed consent and undergo Screening evaluations to determine their eligibility. 
Participants will be selected and categorized into normal renal function or renal impairment 
groups based on their eGFR (using the CKD-EPI equation).
Eligible participants will be admitted to the CRU on Day -1 (at least 12 hours prior to the
dosing of PF-07321332 on Day 1) and will be confined in the CRU until Day 3. On the 
evening of Day -1, participants will receive a single 100 mg dose of ritonavir (-12 hour 
relative to PF-07321332 dosing). On the morning of Day 1, the participants will receive a 
single dose of 100 mg PF-07321332 with a 100 mg dose of ritonavir after a fast of at least 
10 hours. Ritonavir, 100 mg, will continue to be dosed at 12 and 24 hours post
PF-07321332 dosing to ensure maintenance of the PK boosting effect. Serial blood and 


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urine samples at specified intervals will be collected up to 48 hours post-dose for plasma and 
urine PK assessments. 
Safety assessments will be performed during Screening, on Day -1 prior to dosing, and on 
Day 3. Physical examinations, vital sign measurements, and clinical laboratory tests will be 
conducted, and AEs will be monitored to assess safety. The total participation time (eg, CRU 
confinement time for study procedures) for each participant in this study is approximately 
3 nights/4 days (excluding screening & Follow-Up contact).
A safety follow-up call will be made to participants 28 to 35 days from administration of the 
dose of study intervention.
Number of Participants
Approximately 32 participants may be enrolled to study intervention.
Note: "Enrolled" means a participant's, or his or her legally authorized representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process and screening. A participant will be considered enrolled if the informed consent is 
not withdrawn prior to participating in any study activity after screening. Potential 
participants who are screened for the purpose of determining eligibility for the study, but do 
not participate in the study, are not considered enrolled, unless otherwise specified by the 
protocol.
Intervention Groups and Duration
Each enrolled participant will receive a single 100 mg dose of PF-07321332 administered 
orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at 
-12, 0, 12, and 24 hours relative to PF-07321332 dosing. 
The total planned duration of participation, from the Screening visit to the last Follow-up 
phone call, is approximately up to 9 weeks.
Calculation of eGFR
The following CKD-EPI equation will be used to calculate eGFR (Scr, std denotes serum 
creatinine measured with a standardized assay for serum creatinine):


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If female and SCr is ≤0.7 mg/dL:
eGFR (mL/min/1.73 m2) = 144 × (SCr, std/0.7) – 0.329 × 0.993age (× 1.159, if Black)
If female and SCr is >0.7 mg/dL:
eGFR (mL/min/1.73 m2) = 144 × (SCr, std /0.7) – 1.209 × 0.993age (× 1.159, if Black)
If male and SCr is ≤0.9 mg/dL:
eGFR (mL/min/1.73 m2) = 141 × (SCr, std /0.9) – 0.411 × 0.993age (× 1.159, if Black)
If male and SCr is >0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr, std /0.9) – 1.209 × 0.993age (× 1.159, if Black)
Note that the value of eGFR, which is directly obtained from the laboratory or calculated 
using the equation above, is generally normalized to an average body size of 1.73 m2 for 
diagnosis, prognosis and treatment of renal disease. In terms of clearance of renally filtered 
drugs (including secreted drugs), renal elimination capacity is related to absolute GFR 
in mL/min. To use the CKD-EPI-derived, BSA-adjusted value of eGFR to obtain absolute 
GFR (mL/min) for renal disease classification or participant assignment into different renal 
disease groups, this value should be multiplied by the individual participant’s BSA 
(ie, measured BSA/1.73 m2). The BSA of an individual can be calculated by the following 
formula as described below:
BSA = (Weight0.425 × Height0.725) × 0.007184
In summary, GFR in mL/min calculated as below will be used for renal impairment group 
placement: 
Step 1: Obtain the CKD-EPI-derived eGFR:
Step 2: Convert the CKD-EPI-derived, BSA-adjusted eGFR obtained above to absolute 
GFR (mL/min) for eligibility assessment using the following equation: 

eGFR (mL/min) = eGFR (mL/min/1.73m2) × participant’s BSA, where BSA is 
calculated as BSA = (Weight0.425 × Height0.725) × 0.007184.
CLCR will also be estimated from a spot serum creatinine measurement using the following 
C-G equation:
CLCR (mL/min) = (140 – age [years]) × total body weight (kg) × (0.85 for females)
72 × serum creatinine (mg/dL)


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Note that eGFR calculated by the CKD-EPI equation will be used for categorization of 
degrees of renal impairment. Nevertheless, renal function will be estimated using both C-G 
and CKD-EPI equations in this study and dose recommendations will be made using both 
C-G and CKD-EPI equations.
To be enrolled into the study, participant must demonstrate stable renal function, 
with ≤25% change based upon screening S1 eGFR and screening S2 eGFR (calculated by 
the CKD-EPI equation). The S2 eGFR assessment should be performed between 3 to 14 days 
after the S1 eGFR assessment. The average of these 2 eGFR values will be used for group 
placement based on the renal function classification category.

If the renal function stability criterion is met and the renal function classification 
category remains the same between S1 eGFR and the average of the S1 and 
S2 eGFRs, participant will be eligible for enrollment.

If the renal function stability criterion is not met, participant will be screen failed.

If the renal function stability criterion is met but the renal function classification 
category changes between S1 eGFR and the average of the S1 and S2 eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether 
the participant will be eligible for enrollment. 
Please see Table 2 below regarding demonstration of stable renal function:
Table 2.
Criteria to Establish Stable Renal Function
Renal function Measurement
eGFR (mL/min)
Criterion for stability
S1
G1
N/A
S2 (Within 3 to 14 days after S1)
G2
D=|G2-G1|×100/G1a
If D ≤25%; stable
If D >25%; not stable
a.
Parenthesis of | | represents absolute values.
2.2. Study Objectives
2.2.1. Primary Objectives

Part 1: To evaluate the effect of mild (if applicable) and moderate renal impairment 
on the PK of PF-07321332, following a single oral dose administration of 
PF-07321332 pharmacokinetically boosted with ritonavir.

Part 2: To evaluate the effect of severe renal impairment on the PK of PF-07321332, 
following a single oral dose administration of PF-07321332 pharmacokinetically 
boosted with ritonavir.


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2.2.2. Secondary Objectives

To evaluate the safety and tolerability of PF-07321332 and ritonavir, following a 
single oral dose administration of PF-07321332 pharmacokinetically boosted with 
ritonavir, in participants with renal impairment and in healthy participants with 
normal renal function.

To characterize additional PK parameters of PF-07321332 following a single oral 
dose of PF-07321332 pharmacokinetically boosted with ritonavir by renal function.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
No formal interim analysis will be conducted for this study. However, as this is an open
label study, the sponsor may conduct unblinded reviews of the data during the course of the
study for the purpose of safety assessment, facilitating PK/PD modeling, and/or supporting 
clinical development.
Final analysis will follow the official database release.  As this will be an open-label study, 
there is no formal unblinding of the randomization code.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No statistical hypothesis will be tested in this study.
4.2. Statistical Decision Rules
There are no statistical decision rules.
5. ANALYSIS SETS
5.1. Pharmacokinetic (PK) Analysis Set
5.1.1. Concentration Analysis Set
The PK concentration population will be defined as all participants treated in whom at least 
1 plasma concentration value is reported.
5.1.2. Parameter Analysis Set
The PK parameter analysis population is defined as all participants dosed who have at least 
1 of the PK parameters of primary interest.
5.2. Pharmacodynamic Analysis Set
None.


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5.3. Safety Analysis Set
All participants randomly assigned to study intervention and who take at least 1 dose of 
study intervention. Participants will be analyzed according to the product they actually 
received.
5.4. Other Analysis Sets
None.
5.5. Treatment Misallocations 
All analyses will be performed on an “as-treated” basis and will not include data from 
participants who are randomized but not treated.
If a participant takes a treatment that is not consistent with the treatment they are randomized 
to, for example takes a treatment out of sequence or takes the same treatment twice, then they 
will be reported under the treatment that they actually receive for all safety, and PK analyses, 
where applicable.
5.6. Protocol Deviations
Participants who experience events that may affect their PK profile (eg, lack of compliance 
with dosing) may be excluded from the PK analysis.  At the discretion of the 
pharmacokineticist a concentration value may also be excluded if the deviation in sampling 
time is of sufficient concern or if the concentration is anomalous for any other reason.
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
5.6.1. Deviations Assessed Prior to Randomization
At Screening, the investigator will assess participants against the inclusion and exclusion 
criteria as set out in Sections 5.1 and 5.2 of the protocol.
5.6.2. Deviations Assessed Post-Randomization
A full list of protocol deviations for the study report will be compiled prior to database 
closure.  Any significant deviation from the protocol will be reviewed prior to database 
closure and a decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
None.
6.2. Safety Endpoints
Any events occurring following start of treatment or increasing in severity will be counted as 
treatment emergent.


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Events that occur in a non-treatment period (for example, Washout or Follow-up) will be 
counted as treatment emergent and attributed to the previous treatment taken.
The following data are considered in standard safety assessments (see protocol for collection 
days and list of parameters):

adverse events,

laboratory data,

vital signs data,

ECG results.
6.3. Other Endpoints
6.3.1. PK Endpoints
Blood samples for PK analysis of PF-07321332 will be taken according to the Schedule of 
Activities given in the protocol.
The following PK parameters will be calculated for PF-07321332 (if possible) from the 
concentration-time data using standard noncompartmental methods:
Table 3.
Noncompartmental PK Parameters
PK Parameter
Analysis Scale
PF-07321332
AUClast
ln
A, D
AUCinf*
ln
A, D
Cmax
ln
A, D
C12
R
D
C24
R
D
Tmax
R
D
t1/2*
R
D
CL/F*
R
D
Vz/F*
R
D
Key:
A=analyzed using statistical model, D=displayed with descriptive statistics,
ln=natural-log transformed, R=raw (untransformed), *=if data permits.
If urine samples are need to be analyzed, the following urine PK parameters (Table 4) will 
be calculated for PF-07321332 (as data permit):


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Table 4.
Urine PK Parameters
PK Parameter
Analysis Scale
PF-07321332
Ae48
R
D
Ae48%
R
D
CLr
R
D
Key:
D=displayed with descriptive statistics, R=raw (untransformed).
6.3.2. PD Endpoints
None.
6.4. Covariates
None.
7. HANDLING OF MISSING VALUES
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
7.1. Concentrations Below the Limit of Quantification
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification.)
7.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample).
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 
50% of the data are missing.
7.3. Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (ie, not calculated). (Note that NC values will not be generated beyond 
the day that a participant discontinues).


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In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular treatment with ≥3 evaluable measurements.  For statistical 
analyses (ie, analysis of variance), PK parameters coded as NC will also be set to missing; 
and analyses will not be performed for a particular parameter if more than 50% of the data 
are NC.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event such as vomiting before all the compound is adequately absorbed in 
the body), this will be footnoted in summary tables and will not be included in the calculation 
of summary statistics or statistical analyses.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical Methods
8.2. Statistical Analyses
ANOVA will be used to compare the natural log transformed AUCinf (or AUClast if AUCinf
cannot be reliably estimated) and Cmax for PF-07321332 between normal renal function 
group (Reference) and each impaired renal function group separately as applicable (Test). 
Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs will 
be obtained from the model. The adjusted mean differences and 90% CIs for the differences 
will be exponentiated to provide estimates of the ratio of the adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. If substantial differences in demographic 
characteristics between healthy and impaired participants are observed, weight and age may 
be explored as covariates.
Box and whisker plots for individual participant parameters (AUCinf and Cmax) will be
constructed by renal function group and overlaid with geometric means.
For summary statistics and median/mean plots by sampling time, the nominal PK sampling 
time will be used. For individual participant plots by time, the actual PK sampling time will 
be used.
Linear regression will be used to analyze the potential relationship between appropriate PK
parameters (CL/F or CLr, and Vz/F) and renal function (eGFR). Estimates of the slope and, 
intercept, together with their precision (90% CI), and the coefficient of determination will be 
obtained from the model.
Plots of PK parameters (CL/F or CLr, and Vz/F) versus renal function (eGFR) will be 
constructed. A regression line and 90% confidence region for the PK parameters and eGFR 
will be included if appropriate. Vertical lines for the renal function group cut-off values will 
also be presented on the plots. Different symbols will be used to identify participants from 
different renal function groups.


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Residuals from the model will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the clinical study report.  If there are major 
deviations from normality or outliers then the effect of these on the conclusions will be 
investigated through alternative transformations and/or analyses excluding outliers.  
Justification for any alternative to the planned analysis will be given in the report of the 
study.
Table 5.
PK Parameters to be Summarized Descriptively by Cohort
Parameter
Summary Statistics
AUCinf, AUClast,
Cmax, C12, C24, 
t1/2, CL/F, Vz/F
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum, geometric mean and geometric cv%.
t1/2
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum.
Tmax
N, median, minimum, maximum.
Supporting data from the estimation of t½, AUCinf will be listed by Cohort: terminal phase 
rate constant (kel); goodness of fit statistic from the log-linear regression (r2); the percent of
AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of time points 
used in the estimation of kel.  This data may be included in the clinical study report.
Presentations for PF-07321332 concentrations will include:

A listing of all concentrations sorted by participant ID, period and nominal time 
postdose.  The concentration listing will also include the actual times.  Deviations 
from the nominal time will be given in a separate listing.

A summary of concentrations by cohort and nominal time postdose, where the set of 
statistics will include n, mean, median, standard deviation, coefficient of variation 
(cv), minimum, maximum and the number of concentrations above the lower limit of 
quantification.

Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose by cohort (all cohorts on the same plot per scale, based on the 
summary of concentrations by cohort and time postdose).

Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by cohort (all cohorts on the same plot per scale, based on the summary 
of concentrations by cohort and time postdose).

Individual concentration time plots by cohort (on both linear and semi-log scales) 
against actual time postdose (there will be separate spaghetti plots for each cohort per 
scale).


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
A listing of all urine concentration intervals sorted by renal function group (present in 
heading), participant ID and nominal collection duration postdose.
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual participant plots by time, the actual PK sampling time will 
be used.
8.3. Safety Analysis
A set of summary tables split by cohort will be produced to evaluate any potential risk 
associated with the safety and toleration of administering study treatments.
8.3.1. Treatment and Disposition of Participants
Participant evaluation groups will show end of study participant disposition and will show 
which participants were analyzed for pharmacokinetics, as well as for safety (adverse events 
and laboratory data).  Frequency counts will be supplied for participant discontinuation(s) by 
cohort.
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic and Clinical Examination Data
A breakdown of demographic data will be provided for age, race, weight, body mass index, 
and height.  Each will be summarized by sex at birth and ‘All Participants’ in accordance 
with the sponsor reporting standards.
8.3.3. Discontinuation(s)
Participant discontinuations, temporary discontinuations or dose reductions due to adverse 
events will be detailed and summarized by cohort.
Data will be reported in accordance with the sponsor reporting standards.
8.3.4. Adverse Events
Adverse events will be reported in accordance with the sponsor reporting standards by 
cohort.
8.3.5. Laboratory Data
Laboratory data will be listed in accordance with the sponsor reporting standards.
8.3.6. Vital Signs Data
Supine blood pressure, pulse rate, respiratory rate and oral temperature will be measured at 
the protocol specified timepoints.
These data will be listed in accordance with the sponsor reporting standards.


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8.3.7. ECG Data
ECG data will be listed in accordance with the sponsor reporting standards.
8.3.8. Other Safety Data
None.
8.3.9. Concomitant Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
8.3.10. Screening and Other Special Purpose Data
The screening data with the exception of demography and lab creatine data will not be 
brought in-house, and therefore will not be listed.
 
CCI


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9. REFERENCES
None.


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10. APPENDICES
Appendix 1. SAS CODE FOR ANALYSES

An example of the PROC Mixed code is provided below for ANOVA:
proc mixed data = tab.pk covtest alpha=0.1;
class group;
model l&var = group / S covb alpha=0.1 CL DDFM=KR;
repeated/type=un subject=subjid group=group R;
lsmeans group;
estimate 'Moderate vs Normal'
group 1 0 -1 0;
estimate 'Mild vs Normal'
group 0 1 -1 0;
estimate 'Severe vs Normal'
group 0 0 -1 1;
ods output lsmeans = lsmeans&var;
ods output solutionf = solution&var;
run;
/* Letter assignments for group within the estimate statement above are as follows;
A = Moderate (Test);
B = Mild (Test);
C = Normal (Reference);
D = Severe (Test) */;

Linear Regression Example code (Relationship between PK parameters (CL/F or 
CLr and Vz/F) and renal function (eGFR):
Proc glm data=tab.pk
class trt;
model &var= trt  &var1/ solution clparm alpha=0.1;
ods ‘FitStatistics’ out=Rsq&var;
ods 'Modelanaova' out=tst&var;
ods ‘Parameterestimates’ out=pe&var;
run;
Notes: 
&var   = [CL/F or CLr] /  Vz/F
&var1 = eGFR