Clinical trial NCT05652647
Conditions: Healthy Participants
Keywords: Absorption Distribution Metabolism Elimination Bioavailability Fraction absorbed Mass balance Healthy Males
Sponsor: Pfizer
Start date: 2022-12-21; Completion date: 2023-03-15
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this clinical trial is to learn about how much PF-07081532 will be taken up and processed by healthy male participants. The study consists of two parts, called study periods. In Period 1, participants will take one dose of PF-07081532 by mouth. In Period 2, participants will take one dose by mouth and one dose as an injection through a vein at the study clinic.

In Period 1, participants will stay at the clinic site for up to 21 days. In Period 2, they will stay at the clinic site for 7 days. During their stays, participants will have their blood, urine, and feces collected by the study doctors several times. We will measure the level of PF-07081532 in participants' blood, urine, and feces samples. This will help us know how much the study medicine is getting taken in by the body. At the end of the study, participants will be contacted by phone to check in. Participants will be involved in this study for about 12 weeks.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Oral [14C]PF-07081532 intervention 2: Oral PF-07081532 and IV [14C]PF-07081532
Intervention descriptions: intervention 1: A single oral dose of \[14C\]PF-07081532, will be administered as a liquid formulation in study period 1. intervention 2: In study period 2: a single, oral, unlabeled dose of PF-07081532 will be administered as a liquid formulation. Approximately 1 hours after the administration of the unlabeled oral dose, a single dose of \[14C\]PF-07081532 will be administered via intravenous infusion.

Protocol documents:
Prot_000.pdf: 
PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
 
A PHASE 1, OPEN-LABEL, 2-PERIOD, FIXED SEQUENCE STUDY TO 
INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND 
EXCRETION OF [14C]PF-07081532 AND TO ASSESS THE ABSOLUTE 
BIOAVAILABILITY AND FRACTION ABSORBED OF PF-07081532 IN HEALTHY 
MALE PARTICIPANTS USING A [14C]-MICROTRACER APPROACH 
 
 
Study Intervention Number: 
PF-07081532 
Study Intervention Name: 
NA 
US IND Number: 
CCI 
 
EudraCT/CTIS Number: 
NA 
ClinicalTrials.gov ID: 
Not Available 
Pediatric Investigational Plan Number: 
NA 
Protocol Number: 
C3991006 
Phase: 
1 
Brief Title: Phase 1 Study in Healthy Male Participants to Assess ADME Properties of 
[14C]PF-07081532 
 
 
 
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. 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
 
Document History 
 
Document 
Version Date 
Original protocol 
30 September 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 
 
Page 2  
Type text here 


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Protocol C3991006 
Final Protocol, 30 September 2022 
Page 3 
 
 
TABLE OF CONTENTS 
LIST OF TABLES ..................................................................................................................... 8 
1. PROTOCOL SUMMARY ..................................................................................................... 9 
1.1. Synopsis ..................................................................................................................... 9 
1.2. Schema..................................................................................................................... 16 
1.3. Schedule of Activities .............................................................................................. 16 
2. INTRODUCTION ................................................................................................................ 21 
2.1. Study Rationale ........................................................................................................ 21 
2.2. Background .............................................................................................................. 21 
2.2.1. Nonclinical Pharmacology .......................................................................... 21 
2.2.2. Nonclinical Pharmacokinetics and Metabolism .......................................... 21 
2.2.3. Nonclinical Safety ....................................................................................... 22 
2.2.4. Clinical Overview ....................................................................................... 22 
2.2.4.1. Clinical Safety ........................................................................... 23 
CCI 
 .. 23 
2.3. Benefit/Risk Assessment ......................................................................................... 24 
2.3.1. Risk Assessment ......................................................................................... 24 
2.3.2. Benefit Assessment ..................................................................................... 26 
2.3.3. Overall Benefit/Risk Conclusion ................................................................ 26 
3. OBJECTIVES AND ENDPOINTS ..................................................................................... 27 
4. STUDY DESIGN ................................................................................................................. 28 
4.1. Overall Design ......................................................................................................... 28 
4.2. Scientific Rationale for Study Design ..................................................................... 29 
4.2.1. Choice of Contraception/Barrier Requirements .......................................... 31 
4.2.2. Collection of Retained Research Samples ................................................... 31 
4.3. Justification for Dose ............................................................................................... 31 
4.4. End of Study Definition ........................................................................................... 32 
5. STUDY POPULATION ...................................................................................................... 32 
5.1. Inclusion Criteria ..................................................................................................... 32 
5.2. Exclusion Criteria .................................................................................................... 33 
5.3. Lifestyle Considerations .......................................................................................... 35 
5.3.1. Contraception .............................................................................................. 35 
PFIZER CONFIDENTIAL 


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5.3.2. Meals and Dietary Restrictions .................................................................. 35 
5.3.2.1. Dietary Fiber Supplementation ................................................. 36 
5.3.3. Caffeine, Alcohol, and Tobacco ................................................................. 37 
5.3.4. Activity ...................................................................................................... 37 
5.4. Screen Failures ........................................................................................................ 37 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................. 37 
6.1. Study Intervention(s) Administered ........................................................................ 38 
6.1.1. Administration ............................................................................................ 39 
6.2. Preparation, Handling, Storage, and Accountability .............................................. 39 
6.2.1. Preparation and Dispensing ........................................................................ 40 
6.3. Assignment to Study Intervention .......................................................................... 40 
6.4. Blinding .................................................................................................................. 41 
6.4.1. Blinding of Participants .............................................................................. 41 
6.4.2. Blinding of Site Personnel .......................................................................... 41 
6.4.3. Blinding of the Sponsor ............................................................................. 41 
6.5. Study Intervention Compliance .............................................................................. 41 
6.6. Dose Modification .................................................................................................. 41 
6.7. Continued Access to Study Intervention After the End of the Study ..................... 41 
6.8. Treatment of Overdose ........................................................................................... 41 
6.9. Prior and Concomitant Therapy .............................................................................. 42 
6.9.1. Rescue Medicine ........................................................................................ 42 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................... 43 
7.1. Discontinuation of Study Intervention .................................................................... 43 
7.2. Participant Discontinuation/Withdrawal From the Study ...................................... 43 
7.2.1. Withdrawal of Consent .............................................................................. 44 
7.3. Lost to Follow-up ................................................................................................... 44 
8. STUDY ASSESSMENTS AND PROCEDURES .............................................................. 44 
8.1. Administrative Procedures ...................................................................................... 44 
8.2. Efficacy Assessments ............................................................................................. 45 
8.3. Safety Assessments ................................................................................................. 45 
8.3.1. Physical Examinations ............................................................................... 46 


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8.3.2. Vital Signs ................................................................................................... 46 
8.3.2.1. Blood Pressure and Pulse Rate .................................................. 46 
8.3.3. Electrocardiograms ...................................................................................... 47 
8.3.4. Clinical Safety Laboratory Assessments ..................................................... 47 
8.3.5. COVID-19 Specific Assessments ............................................................... 48 
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................. 48 
8.4.1. Time Period and Frequency for Collecting AE and SAE Information ....... 49 
8.4.1.1. Reporting SAEs to Pfizer Safety ............................................... 49 
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF ................... 49 
8.4.2. Method of Detecting AEs and SAEs ........................................................... 50 
8.4.3. Follow-Up of AEs and SAEs ...................................................................... 50 
8.4.4. Regulatory Reporting Requirements for SAEs ........................................... 50 
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure ..................................................... 51 
8.4.5.1. Exposure During Pregnancy ...................................................... 51 
8.4.5.2. Exposure During Breastfeeding ................................................. 52 
8.4.5.3. Occupational Exposure .............................................................. 53 
8.4.6. Cardiovascular and Death Events ................................................................ 53 
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................. 53 
8.4.8. Adverse Events of Special Interest .............................................................. 53 
8.4.8.1. Lack of Efficacy ........................................................................ 53 
8.4.9. Medical Device Deficiencies ...................................................................... 53 
8.4.10. Medication Errors ...................................................................................... 53 
8.5. Pharmacokinetics ..................................................................................................... 54 
8.5.1. Analysis of Plasma ...................................................................................... 55 
8.5.1.1. Period 1 Plasma Analysis of PF-07081532 Using 
LC/MS/MS ........................................................................................ 55 
8.5.1.2. Period 1 Plasma Analysis of Total Radioactivity [14C] 
Using AMS ........................................................................................ 55 
8.5.1.3. Period 1 Plasma Analysis for Metabolite Profiling Using 
AMS and UPLC-HRMS .................................................................... 55 
8.5.1.4. Period 2 Plasma for Analysis of Oral, Unlabeled PF- 
07081532, Using LC/MS/MS ........................................................... 56 


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8.5.1.5. Period 2 Plasma for Analysis of IV [14C]PF-07081532 
Using AMS and UPLC-HRMS ......................................................... 56 
8.5.2. Analysis of Urine ....................................................................................... 56 
8.5.3. Analysis of Feces ....................................................................................... 57 
8.5.4. Emesis Collection ...................................................................................... 57 
CCI 
.57 
8.5.6. Analysis of Dosing Formulation and Determination of Administered 
Dose ................................................................................................................. 58 
8.6. Genetics .................................................................................................................. 58 
.58 
.58 
8.7. Biomarkers .............................................................................................................. 58 
8.8. Immunogenicity Assessments ................................................................................ 58 
8.9. Health Economics ................................................................................................... 58 
CCI 
.59 
9. STATISTICAL CONSIDERATIONS ................................................................................ 59 
9.1. Statistical Hypothesis ............................................................................................. 59 
9.2. Analysis Sets ........................................................................................................... 59 
9.3. Statistical Analyses ................................................................................................. 60 
9.3.1. General Considerations .............................................................................. 60 
9.3.2. Primary Endpoint(s) Analysis .................................................................... 61 
9.3.2.1. Extent of Excretion (Period 1) .................................................. 61 
9.3.2.2. Metabolite Profiling and Metabolite Identification (Period 
1) 
 .................................................................................................. 61 
9.3.3. Secondary Endpoint(s) Analysis ................................................................ 61 
9.3.3.1. Pharmacokinetic Parameters ..................................................... 61 
9.3.3.2. Safety Analyses ........................................................................ 65 
9.3.4. Tertiary/Exploratory Endpoint(s) Analysis ................................................ 66 
CCI 
 .. 66 
9.3.4.2. Cumulative Rate of Excretion (Period 1) ................................. 66 
CCI 


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9.3.4.3. Pharmacokinetics Parameters (Oral Unlabeled PF- 
07081532 - Period 2) ........................................................................ 66 
9.3.5. Other Analyses ........................................................................................... 66 
9.4. Interim Analyses ..................................................................................................... 66 
9.5. Sample Size Determination .................................................................................... 66 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.......................................................................................................... 67 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............... 67 
10.1.1. Regulatory and Ethical Considerations .................................................... 67 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................ 67 
10.1.2. Financial Disclosure ................................................................................. 68 
10.1.3. Informed Consent Process ....................................................................... 68 
10.1.4. Data Protection ......................................................................................... 69 
10.1.5. Committees Structure ............................................................................... 69 
10.1.5.1. Data Monitoring Committee ................................................... 69 
10.1.6. Dissemination of Clinical Study Data ...................................................... 70 
10.1.7. Data Quality Assurance ............................................................................ 71 
10.1.8. Source Documents ................................................................................... 72 
10.1.9. Study and Site Start and Closure .............................................................. 72 
10.1.10. Publication Policy .................................................................................. 73 
10.1.11. Sponsor’s Medically Qualified Individual ............................................. 74 
10.2. Appendix 2: Clinical Laboratory Tests ................................................................ 75 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ..................................................................... 77 
10.3.1. Definition of AE ....................................................................................... 77 
10.3.2. Definition of an SAE ................................................................................ 78 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ........................................................................... 79 
10.3.4. Reporting of SAEs ................................................................................... 83 
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................ 84 
10.4.1. Male Participant Reproductive Inclusion Criteria ................................... 84 
10.4.2. Female Participant Reproductive Inclusion Criteria ................................ 84 


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10.4.3. Woman of Childbearing Potential ..............................................................84 
10.4.4. Contraception Methods ..............................................................................84 
...85 
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments ........ 86 
10.7. Appendix 7: Kidney Safety: Monitoring Guidelines ............................................. 88 
10.7.1. Laborato1y Assessment of Change in Kidney Function and 
Detection of Kidney Injmy .............................................................................. 88 
10.7.2. Age-Specific Kidney Function Calculation Recommendations ................ 88 
10.7.2.1. Adults (18 Years and Above)-2021 CKD-EPI Equations ....... 88 
10.7.3. Adverse Event Grading for Kidney Safety Laboratory 
Abno1malities .................................................................................................. 88 
10.8. Appendix 8: ECG Findings of Potential Clinical Concern .................................... 89 
.91 
10.10. Appendix 10: Prohibited Concoinitant Medications That May Result in 
DDI ............................................................................................................................ 97 
10.11. Appendix 11: Abbreviations .............................................................................. 101 
11. REFERENCES ................................................................................................................. 105 
 
 
 
Table 1. 
Table 2. 
Table 3. 
 
 
LIST OF TABLES 
Schedule of Activities From Screening Through End of Period 1 ............ 17 
Schedule of Activities From Period 2, Day -1 Through Follow-up ......... 19 
Protocol-Required Safety Laboratory Assessments .................................. 75 
 


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: 
A Phase 1, Open-Label, 2-Period, Fixed Sequence Study to Investigate the Absorption, 
Distribution, Metabolism and Excretion of [14C]PF-07081532 and to Assess the Absolute 
Bioavailability and Fraction Absorbed of PF-07081532 in Healthy Male Participants Using a 
[14C]-Microtracer Approach 
Brief Title: 
Phase 1 Study in Healthy Male Participants to Assess ADME Properties of 
[14C]PF-07081532 
Regulatory Agency Identification Number(s): 
 
US IND Number: 
CCI  
 
EudraCT/CTIS Number: 
NA 
ClinicalTrials.gov ID: 
Not Available 
Pediatric Investigational Plan Number: 
NA 
Protocol Number: 
C3991006 
Phase: 
1 
Rationale: 
The purpose of the study is to assess the metabolism and extent of excretion of 
[14C]PF-07081532 in urine and feces, following oral administration, in the fed state, in 
healthy male participants. This information will enable assessment of clearance mechanisms 
of PF-07081532 as well as identify disproportionate metabolites that should be qualified to 
adhere to the ICH M3 (R2) MIST guidance. In addition, this study will characterize the 
fraction of dose absorbed and the bioavailability of orally administered PF-07081532 in the 
fed state, in reference to an IV dose of [14C]PF-07081532, while it will also assess PK 
parameters following both oral and IV administration of [14C]PF-07081532. 


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Objectives and Endpoints: 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• To characterize the extent of excretion of total 
radioactivity in urine and feces following 
administration of a single oral dose of 
[14C]PF-07081532. 
• Total recovery of radioactivity in urine and feces, and 
both routes combined, expressed as a percent of total 
oral radioactive dose administered. 
• To characterize the metabolic profile and identify 
circulating and excreted metabolites following 
administration of a single oral dose of 
[14C]PF-07081532. 
• Metabolic profiling/identification and determination of 
relative abundance of [14C]PF-07081532 and the 
metabolites of [14C]PF-07081532 in plasma, urine, and 
feces. 
Secondary: 
Secondary: 
• To quantify plasma PK parameters of PF-07081532 
and total radioactivity following administration of a 
single oral dose of [14C]PF-07081532. 
• AUClast, Cmax, Tmax, and if data permit, AUCinf, t½, CL/F 
(PF-07081532 only), and Vz/F (PF-07081532 only), to 
describe single oral dose PK in Period 1 of: 
• 
Total radioactivity in plasma; 
• 
PF-07081532 in plasma. 
• To quantify plasma PK parameters of 
[14C]PF-07081532, following administration of a 
single, IV, microdose of [14C]PF-07081532. 
• [14C]PF-07081532 parameters to describe IV plasma PK: 
AUClast, AUClast(dn), Cmax, Cmax(dn), Tmax, and if data 
permit, AUCinf, AUCinf(dn), t½, CL, Vss and MRT. 
• To determine the absolute oral bioavailability (F) of 
PF-07081532 following administration of a single oral 
dose of PF-07081532 compared to a single IV 
microdose of [14C]PF-07081532. 
• F computed from plasma AUCinf (if data permit, 
otherwise AUClast) of oral unlabeled PF-07081532 in 
Period 2 and IV microdose of [14C]PF-07081532 in 
Period 2. 
• To determine the fraction of dose absorbed (Fa) 
following administration of a single oral dose of 
[14C]PF-07081532. 
• Fa calculated from ratio of total urinary radioactivity 
following oral administration of [14C]PF-07081532 in 
Period 1 and IV administration of [14C]PF-07081532 in 
Period 2. 
• To evaluate safety and tolerability of PF-07081532, 
administered as a single oral dose of 
[14C]PF-07081532 or a single oral dose of 
PF-07081532 followed by administration of a single 
IV microdose of [14C]PF-07081532. 
• Safety endpoints including physical examinations, 
adverse events, clinical laboratory measurements, vital 
signs, and ECG. 
Overall Design: 
This study is a Phase 1, open-label, 2-period, fixed sequence study to characterize the 
metabolic profile and routes of excretion of oral [14C]PF-07081532 and to evaluate the 
absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-07081532 in healthy male 
participants. 
Number of Participants: 
Approximately 6 participants will be enrolled in the study. 
Note: "Enrolled" means a participant's, or their legally authorized representative’s, agreement 
to participate in a clinical study following completion of the informed consent process and 
assignment to and dosing with study intervention. A participant will be considered enrolled if 


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PFIZER CONFIDENTIAL 
Page 11 
 
 
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. 
Study Population: 
Inclusion and exclusion criteria are listed below: 
Inclusion Criteria 
Participants must meet the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Male participants must be 18 to 60 years of age, inclusive, at the time of signing the 
ICD. 
2. Male participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, blood pressure and pulse rate 
measurement, standard 12-lead ECG, and laboratory tests. 
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). 
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures including 
collection of blank urine and feces samples prior to dosing on Day 1, Period 1. 
5. Capable of giving signed informed consent, which includes compliance with the 
requirements listed in the ICD and in this protocol. 
Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded: 
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing). 
• Any condition possibly affecting drug absorption (eg, gastrectomy, 
cholecystectomy). 
• Positive testing at screening for HIV, HBsAg, HBcAb, HBsAb or HCVAb. Note: 
A positive HBsAb due to hepatitis B vaccination is permissible. 
2. Personal or family history of MTC or MEN2, or participants with suspected MTC per 
the investigator’s judgement. 


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3. History of irregular bowel movements (eg, irritable bowel syndrome, frequent 
episodes of diarrhea, or constipation defined by less than 1 bowel movement on 
average per 2 days) or lactose intolerance. 
4. Other medical or psychiatric condition including recent (within the past year of 
screening) or active suicidal ideation/behavior or laboratory abnormality or other 
conditions or situations related to COVID-19 pandemic (eg, contact with positive 
case) that may increase the risk of study participation or, in the investigator’s 
judgment, make the participant inappropriate for the study. 
5. Use of any prescription or non-prescription drugs and dietary and herbal supplements. 
6. Previous administration with an investigational product (drug or vaccine) within 
90 days (or as determined by the local requirement) preceding the first dose of study 
intervention used in this study. 
7. Known prior participation (ie, received at least 1 dose of study intervention) in a 
study involving PF-07081532 or known intolerance to a GLP-1R agonist. 
8. A positive urine drug test at screening or admission. 
9. 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. 
10. eGFR <90 mL/min/1.73m2 (calculated with the 2021 CKD-EPI Scr only equation) at 
screening. 
11. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTcF >450 ms, 
complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T 
interval changes suggestive of myocardial ischemia, second- or third- degree AV 
block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT 
interval is >450 ms, this interval should be rate-corrected using the Fridericia method 
only and the resulting QTcF should be used for decision making and reporting. If 
QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice 
and the average of the 3 QTcF or QRS values used to determine the participant’s 
eligibility. Computer-interpreted ECGs should be overread by a physician 
experienced in reading ECGs before excluding a participant. 
12. 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 ≥1.5 × ULN; 


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• 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. 
13. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 
5 (male) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake 
should not exceed 14 units per week (1 unit = 8 ounces [240 mL] beer, 1 ounce 
[30 mL] of 40% spirit, or 3 ounces [90 mL] of wine). 
14. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
15. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is planned to flush IV catheters. 
16. Total [14C] radioactivity measured in plasma at screening exceeding 11 mBq/mL. 
17. Participants with current use of tobacco- and/or nicotine-containing products 
exceeding equivalent of 5 cigarettes per day. 
18. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members. 


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Study Arms and Duration: 
Study Intervention(s) 
Intervention Name 
[14C]PF-07081532 
PF-07081532 
[14C]PF-07081532 
Arm Name 
(group of 
participants 
receiving a specific 
treatment or no 
treatment) 
Period 1 
Period 2 
Period 2 
Type 
Drug 
Drug 
Drug 
Dose Formulation 
Extemporaneously prepared 
liquid formulation 
Extemporaneously 
prepared liquid 
formulation 
Extemporaneously prepared 
liquid formulation 
Unit Dose Strength(s) 
NA 
NA 
NA 
Dosage Level(s) 
30 mg, single dose 
30 mg, single dose 
100 µg, single dose 
Route(s) of 
Administration 
Oral 
Oral 
IV infusion 
Use 
Experimental 
Experimental 
Experimental 
IMP or NIMP/AxMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally by the 
sponsor. Refer to the SAI 
Provided centrally by the 
sponsor. Refer to the SAI 
Provided centrally by the 
sponsor. Refer to the SAI 
Packaging and 
Labeling 
[14C]PF-07081532 components 
will be supplied by Pfizer, as 
bulk API and, where necessary, 
bulk excipients for the 
manufacture of the [14C] 
labeled oral liquid formulation 
Unlabeled PF-07081532 
will be provided by 
Pfizer as bulk powders 
for extemporaneous 
preparation 
[14C]PF-07081532 components 
will be supplied by Pfizer, as 
bulk API and, where necessary, 
bulk excipients for the 
manufacture of the [14C] 
labeled IV liquid formulation 
Current/Former 
Name(s) or Alias(es) 
[14C]PF-07081532 
PF-07081532 
[14C]PF-07081532 
Study Arm(s) 
Arm Title 
Period 1 
Period 2 
Arm Type 
Experimental 
Experimental 
Arm Description 
Oral dose of 30 mg PF-07081532 
containing 250 nCi [14C] 
([14C]PF-07081532) will be 
administered as an 
extemporaneously prepared liquid 
formulation, approximately 
10 minutes after completion of 
breakfast. 
Unlabeled oral dose of PF-07081532, 30 mg will 
be administered as an extemporaneously prepared 
liquid formulation, approximately 10 minutes 
after completion of breakfast. Approximately 
1 hour after the administration of the unlabeled 
oral dose, a single dose of 100 µg PF-07081532 
containing 250 nCi [14C] ([14C]PF-07081532) will 
be administered IV, as an infusion over 
approximately 15 minutes. 
Associated Intervention 
Labels 
[14C]PF-07081532 
PF-07081532, [14C]PF-07081532 


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Page 15 
 
 
Statistical Methods: 
A sample size of approximately 6 participants has been chosen based on the industry 
standard sample size for mass balance and radiolabeled microtracer studies and in line with 
latest FDA draft guidance (May 2022). This sample size was not chosen based on any 
empirical data or hypothesis testing criteria. The sample size has been selected to ensure that 
6 participants provide evaluable data after completing Period 1; with intent to replace 
participants who prematurely withdraw (or offer non-evaluable or partially evaluable data). 
In Period 2, participants who are prematurely withdrawn may be replaced at the discretion of 
sponsor. 
Extent of excretion (Period 1 only): Radioactivity excreted in urine and/or feces will be 
reported as the percentage of the administered radioactivity excreted at each time interval, 
cumulatively through that interval and the total percent of dose recovered in urine and/or 
feces. Percent recovery and cumulative recovery of total radioactivity in urine, feces and 
emesis (if any) will be determined based on total administered dose. 
Metabolic Profiling and Metabolite Identification (Period 1 only): Major metabolites of 
PF-07081532 in plasma, urine, and feces following oral dose of [14C]PF-07081532 will be 
identified, if possible. Contributions of parent and each major metabolite to total radioactivity 
recovered in urine and feces and to circulating radioactivity in plasma will be quantified. 
Results of the metabolic profiling analysis will be detailed in a separate report and will be 
summarized within the CSR. 
Absolute bioavailability (Period 2 only): F will be estimated as the ratio of adjusted 
geometric means of dose-normalized AUCinf (if data permit, otherwise AUClast) for oral 
unlabeled PF-07081532 and IV [14C]PF-07081532 in plasma. 
Fraction absorbed (Fa): Fa will be estimated as the ratio of adjusted geometric means of % of 
administered radioactive dose excreted into urine following oral and IV administration of 
[14C]PF-07081532 in Periods 1 and 2, respectively. Urine radioactivity up to Day 7 will be 
used for Period 1 to match the duration of Period 2 urine collection up to discharge. 
PK parameters (Period 1): Plasma PK parameters of PF-07081532 and total radioactivity 
will be calculated following administration of a single oral dose of [14C]PF-07081532. 
PK parameters (Period 2): Plasma PK parameters of [14C]PF-07081532 will be calculated 
following administration of a single, IV, microdose of [14C]PF-07081532. 
Safety: Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate. 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 16 
 
 
Ethical Considerations: 
Based on available clinical data with PF-07081532, a single 30 mg oral dose (Period 1), and 
a single 30 mg oral dose followed by 100 µg IV dose (Period 2) are anticipated to be safe and 
well tolerated. PF-07081532 is not expected to provide any clinical benefit to healthy 
participants. This study is designed primarily to evaluate the ADME properties of 
PF-07081532. Results from this study will inform and facilitate further clinical development 
of PF-07081532. 
1.2. Schema 
 
 
a. 
See Section 4.1 for details on Period 1 discharge criteria. 
b. At least 21 days of washout is required between dosing in Period 1 and Period 2. 
c. 
In Period 2, participants will be discharged from the CRU on Day 7. 
 
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. 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 17 
 
 
 
Table 1. 
Schedule of Activities From Screening Through End of Period 1 
 
 
 
 
 
 
I.() 
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isit Identifier 
 
ay 
Hours After oral 14C PF-07081532 Dose 
Infonned consent 
Screen 
gs 
 
X 
X 
 
 
X 
X 
Period 1 
ET 
 
-1 
1 
2 3 4  5 
6 
7-213 
0  0.5 1  2  4 
6 
8  10 12 15 24 36 48 72 96 120 
144-480 
 
See ootnote 
X 
X 
x• 
 
X 
X 
X 
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X 
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d 
 
e 
 
 
 
 
' 
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X 
X X X X 
g 
X 
X 
X 
X 
X X X 
X 
X 
X 
X X X X 
X X 
X 
Xk 
1011 
X 
X 
X X X 
X 
X 
X 
X 
X X X X X X 
xt 
X 
X 
Xd 
X 
 
 
 
X 
. 
. 
·inalysis (and microscopy, if 
ded 
X 
Total radioactivity and metabolite IDi 
 
 
X X XXXX 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 18 
 
 
 
 
 
 
 
 
 
 
 
I.() 
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Table 1. 
Schedule of Activities From Screening Through End of Period 1 
 
 Feces sam les for: 
 
Total fecal radioactivity and metabolite II)i 
X 
X 
X XXXX 
X 
Note: for list of abbreviations refer to Appendix 11. 
a. 
See Section 4.1 for details on Period 1 discharge criteria. 
b. Assessment of risk for, symptoms of or testing for COVID-19 may be perfonned at screening, admission to the CRU and/or at other times during the study 
at investigator discretion and according to local site policies. 
c. 
 Complete physical examination, including height and weight, will be conducted at screening or admission of Period 1 only; brief physical exam at other 
time points, for findings during previous PE or new/open AEs, at investigator discretion. 
d. 
Procedures to be perfom1ed on the day of discharge onlv. (see also Section 4.1). 
e. 
Meals will be served throughout inpatient stay, as described in Section 5.3.2. Standardized meals to be served on Day 1. 
0 
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Samples to be collected up to the morning of Day 7 only. 
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h. 
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit. 
1. 
"Blank" pre-dose urine sample to be collected v.rithin the 24 hours prior to dosing. Following oral dosing, each urine void to be collected across intervals of 
0-12 hours, 12-24 hours, and each subsequent 24 hours interval up to discharge from Period 1, as described in Section 8.5.2. 
J. 
"Blank" fecal sample to be collected from at least 1 bowel movement within the 48 hours prior to dosing, which may be collected from home. Following 
oral dosing, all feces excreted will be collected across each 24 hours interval up to discharge from Period 1, as described in Section 8.5.3. 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 19 
 
 
 
 
 
 
 
 
 
 
 
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Table 2. 
Schedule of Activities From Period 2, Day -1 Through Follow-up 
 
Visit Identifier 
Period 2 
FU• ET 
Day 
-1 
1 
2 
3 4 5 
6 
7b 28-35 
Hours Relative to Oral Dosing of Unlabeled 
PF-07081532 
0 0.5 1 1.17 1.25 1.33 1.5 2 4 6 8 10 12 15 24 36 48 72 96 120 144 
Hours Relative to Dosing of (14C)PF-07081532 
(IV infusion start) 
0 0.17 0.25 0.33 0.5 1 
3 5 7 9 11 14 23 35 47 71 95 119 143
Inpatient stay at CRU 
xc
COVID-19 testing/risk assessment' 
See footnote d 
Phvsical examinatiorl 
X 
X 
X 
(Update.)dmg/alcohol/tobacco use 
x•
X 
X 
Review prior & concomitant medications 
x•
X 
X 
Supine 12-lead ECG 
X 
X 
X 
Supine vital si=s (blood pressure and pulse rate) 
X 
X 
X 
Serious and non-serious adverse event monitoring 
X 
X 
X 
X 
Standard mealsg 
X 
X 
X 
Oral Unlabeled PF-07081532 administration 
X 
IV [14C]PF-07081532 (administration as a 15 min 
infusion) 
Xb
Xh 
Blood samples for: 
PK of PF-07081532 
X 
X 
X 
X X X X X X X X X X X X 
X 
X 
X 
PK off14ClPF-07081532 
)Ci 
X 
xi 
X 
X X X X X X X X X X X X X 
X 
X 
Clinical laborato1y after >4-hour fast 
X 
X 
X 
Urine samples for: 
Spot collection for minalysis (and microscopy, if 
needed) 
X 
X 
X 
Total radioactivityi 
Xi 
X 
X 
X 
X X X 
X 
X 
Fecal samples f01·: 
Potential analysis of total radioactivity, [14C]PF- 
07081532 and metabolite ID1: 
Xk
X 
X 
X X X 
X 
X 
Note: for list of abbreviations refer to Appendix 11. 
a. 
Follow-up may be a phone call. 
b. Pruticipants will be discharged on Day 7. 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 20 
 
 
 
 
 
 
 
 -
I- - 
C. 
Participants will be admitted to the CRU on Day -1 of Period 2. At least 21 days washout is required between dosing in Period 1 and Period 2. If a 
participant in Period 1 is not discharged before Day 21, then the pruiicipant may continue directly to Period 2 (see also Section 4.1). 
d. 
Assessment of risk for, symptoms of or testing for COVID-19 may be perfotmed at screening, admission to the CRU and/or at other times during the study 
at investigator discretion ru1d according to local site policies. 
e. 
Will not be perfonned if the pa1ticipru1t was not discharged between Period 1 ru1d Period 2. 
f. 
Brief physical exrun envisioned only for findings dming previous PE or new/open AEs, at investigator discretion. 
g. 
Meals will be served throughout inpatient stay, as described in Section 5.3.2. Standardized meals to be served on Day 1 of Period 2. 
h. IV [14C]PF-0708l 532 dose to be administered as an infusion over approximately 15 minutes (sta1ting at approximately 1 hour after the administration of the 
oral unlabeled PF-07081532 dose). 
(9 
1. 
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PK [14C]PF-0708 l 532 srunple at O hours to be collected immediately before the start of infusion; 0.25-hour sample to be collected immediately after the end 
of infusion. 
Blank urine sample must be collected within the 24 hours prior to dosing. Following oral dosing, each urine void to be collected a.cross intervals of 
1-12 hours (ie, post IV infusion), 12-24 hours, ru1d each subsequent 24 hour-interval up to dischru·ge from Period 2, as described in Section 8.5.2. 
"Blank" fecal sample to be collected from at least 1 bowel movement during the 48 hours pre-dose interval, which may be collected from home. On Day 1 
of Period 2 feces will be collected post IV infusion (ie, at 1-24 h following oral dosing) and thereafter across ea.ch subsequent 24-hour interval up to 
discharge from Period 2, as described in Section 8.5.3. 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 21 
 
 
CCI 
2. INTRODUCTION 
GLP-1 is a neuroendocrine hormone that is predominantly released from the small intestine 
in response to food intake.1 Activation of the GLP-1R stimulates insulin release, inhibits 
glucagon secretion in a glucose-dependent manner, and delays gastric emptying.2,3 In 
addition, GLP-1 has been shown to increase satiety and suppress food intake.4 
PF-07081532 is a potent and selective, orally administered, small molecule GLP-1R agonist 
that is being developed as an adjunct to diet and exercise to improve glycemic control in 
adults with T2DM, and as an adjunct to diet and exercise for chronic weight management in 
adults who are overweight with co-morbidities or who have obesity. 
2.1. Study Rationale 
The purpose of the study is to assess the metabolism and extent of excretion of 
[14C]PF-07081532 in urine and feces, following oral administration, in the fed state, in 
healthy male participants. This information will enable assessment of clearance mechanisms 
of PF-07081532 as well as identify disproportionate metabolites that should be qualified to 
adhere to the ICH M3 (R2) MIST guidance.5 In addition, this study will characterize the 
fraction of dose absorbed and the bioavailability of orally administered PF-07081532, in the 
fed state, in reference to an IV dose of [14C]PF-07081532. The characterization of absorption 
and oral bioavailability will enable BCS classification of PF-07081532. Finally, this study 
will also assess PK parameters following both oral and IV administration of 
[14C]PF-07081532. The data collected in this study will enable further understanding of the 
ADME properties of PF-07081532. 
2.2. Background 
2.2.1. Nonclinical Pharmacology 
Details of the nonclinical pharmacology program are included in the IB. 
2.2.2. Nonclinical Pharmacokinetics and Metabolism 
 
 
 
 
 
PFIZER CONFIDENTIAL 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 22 
 
 
 
Fm1her details of the nonclinical phaimacokinetics and metabolism program are included in 
the IB. 
2.2.3. Nonclinical Safety 
The nonclinical safety profile of PF-07081532 has been adequately characterized to suppo1t 
progression into long-te1m clinical trials. 
PF-07081532 was administered PO to Wistar-Han rats and cynomolgus monkeys in studies 
up to 6 and 9 months in dmation, respectively. PF-07081532 did not result in any mo1tality 
or adverse effects in any of the study parameters or endpoints evaluated. The NOAELs in the 
6-month rat and 9-month monkey ivotal toxici 
studies were the hi est dose levels tested 
 
Studies were conducted to evaluate the effects of PF-07081532 on fertility, reproduction, and 
development in male and female rats, and EFD studies were conducted in rats and rabbits. 
No PF-07081532-related effects were observed in any male or female fe1tility or 
reproductive endpoints evaluated. The NOAELs for female fe1tility and early emb1yonic 
development and for male systemic toxicity and fe1tility were the highest doses evaluated 
and provide sufficient mai·gin over the highest planned clinical dose to suppo1t futme studies. 
Fmther details of the nonclinical toxicology program are included in the IB. 
2.2.4. Clinical Overview 
Two clinical studies (C3991001 and C3991002) have been completed with PF-07081532 in 
which a total of 88 participants have been randomized. Across these studies, 22 healthy adult 
paiticipants, 51 adult paiticipants with T2DM and 15 adult pa1ticipants with obesity have 
been randomized, with a total of 74 unique paiticipants exposed to at least I dose of 
PF-07081532. 
One Phase 1 study, C3991003, is ongoing. This in-patient study to assess safety, tolerability 
and PK of multiple oral doses of PF-07081532 is emolling paiticipants with T2DM and 
paiticipants with obesity to receive PF-07081532 or placebo daily for 42 days. The staiting 
dose for the first coho1t enrolled in this study was 20 mg of PF-07081532, with subsequent 
dose levels dete1mined based on emerging data. While final clinical data from this study are 
not yet available, as of issuance of this protocol, there have been no deaths, SAEs, or AEs of 
severe intensity repo1ted. 
 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 23 
 
 
CCI 
2.2.4.1. Clinical Safety 
The safety profile of PF-07081532 has been assessed in 2 completed clinical studies and, to 
date, administration of PF-07081532 at single doses up to 200 mg and multiple doses up to 
180 mg QD over up to 42 days has been considered safe, with a tolerability profile consistent 
with the mechanism of action and a majority of TEAEs being mild in intensity and in the 
Gastrointestinal Disorders SOC. 
Following single dose administration to healthy adult participants in study C3991001, the 
most frequently reported all-causality TEAEs across all treatment groups were nausea and 
vomiting, with an increased incidence of GI AEs noted at the dose of 200 mg. In the multiple 
ascending dose study, C3991002, the most frequently reported all causality TEAEs included 
nausea in participants with T2DM, and nausea and constipation in participants with obesity. 
Higher incidences of GI TEAEs were observed in the higher dose groups of PF-07081532 
(120 mg QD and 180 mg QD) compared to placebo. There were no clinically significant 
adverse trends in safety laboratory tests, vital signs or ECG parameters in either study with 
increasing PF-07081532 doses. 
Refer to the IB for more detail on these studies, and the known drug class effects of marketed 
GLP-1R agonists. 
 
 
PFIZER CONFIDENTIAL 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 24 
 
 
 
 
 
 
 
 
 
 
 
I.() 
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2.3. Benefit/Risk Assessment 
More detailed info1mation about the known and expected benefits and risks and reasonably expected AEs of PF-07081532, and the 
dmg class effects of marketed GLP-IR agonists, may be found in the IB which is the SRSD for this study. 
2.3.1. Risk Assessment 
 
Potential Risk of Clinical Significanc.e 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Inte1-vention PF-07081532 
Gastrointestinal adverse reactions 
The potential risks are based on product labeling for 
injectable GLP-lR agonists (ie, liraglutide, exenatide, 
semaglutide and dulaglutide). 
Gastrointestinal adverse events, the majority of which 
were mild in intensity, have been observed in the clinical 
program with PF-07081532. 
The single dose and dose level administered in 
this study minimize any potential risk. 
Hypoglycemia 
Clinical trials with injectable GLP-lR agonists have not 
demonstrated an increased risk for hypoglycemia. 
However, when administered in combination with 
anti-diabetic agents that are known to have an increased 
risk of hypoglycemia (such as insulin or sulfonylw-eas), an 
increased risk for hypoglycemia was observed. 
The single dose and dose level administered in 
this study minimize any potential risk. The 
participants enrolled will not have diabetes and 
will not be receiving anti-diabetic agents. Study 
includes inpatient monitoring of the paiticipants 
following administration of a single dose of the 
study intervention. 
Increased hea1t rate 
Based on the product labeling for the injectable GLP-lR 
agonist liraglutide for obesity, mean increases in resting 
hea1t rate ranged 2 to 3 bpm in clinical trials, with some 
pa1ticipants experiencing greater increases in resting heart 
rate, up to 10-20 bpm. 
The single dose and dose level administered in 
this study 1ninimize any potential risk. 
Study includes inpatient observation of the 
participants following administration of a single 
dose of the study intervention. 
Potential risks associated with long-tenn 
dosing of marketed GLP-lR agonists 
include thyroid C-cell tumors, pai1creatitis, 
imoairment in renal function, diabetic 
The potential risks are based on product labeling for 
injectable GLP-lR agonists (ie, liraglutide, dulaglutide, 
exenatide and semaglutide); additional info1mation is 
provided in the IB. 
The single dose and dose level administered in 
this study 1ninimize any potential risk. 
 
 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Phaimacology Protocol Template (01 April 2022) 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
Page 25 
 
 
N 
LL 
 
 
 
 
 
 
 
 
 
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0) 
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Potential Risk of Clinical Signific.anc.e 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
retinopathy complications, acute gallbladder 
disease 
Study includes inpatient monitoring of the 
participants following administration of a single 
dose of the study intervention. 
Participants with a personal or family histo1y of 
MTC or MEN2; with acute pancreatitis or a 
history of chronic pancreatitis are not eligible for 
study entry. 
Other 
Risk of COVID-19 exposure during study 
During the pandemic, study participants could be exposed 
to the SARS-CoV-2 vims dw-ing study pa1ticipation. This 
could lead to increased health risk for this paiticipant and 
others in the study. 
Assessment of risk for, symptoms of or testing for 
COVID-19 may be perf01med at screening, 
admission to the CRU and/or at other times 
dw-ing the study at investigator discretion and 
according to local site policies. 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 26 
 
 
2.3.2. Benefit Assessment 
PF-07081532 is not expected to provide any clinical benefit to healthy participants. This 
study is designed primarily to evaluate the ADME properties of PF-07081532. Results from 
this study will inform and facilitate further clinical development of PF-07081532. 
2.3.3. Overall Benefit/Risk Conclusion 
Based on available clinical data with PF-07081532 (Section 2.2.4 and current IB), a single 
30 mg oral dose (Period 1), and a single 30 mg oral dose followed by 100 µg IV dose 
(Period 2) are anticipated to be safe and well tolerated. Each participant will be exposed to 
approximately 500 nCi over the entire study duration, which includes dosing 
[14C]PF-07081532 in Period 1 and Period 2. This is classed as a microtracer dose, without 
any anticipated risk to study participants. 
Based on the profile of PF-07081532 observed in nonclinical and clinical studies to date, and 
the measures taken as part of the study to minimize risk to study participants, the potential 
risks identified in association with PF-07081532 are justified by the anticipated benefits that 
may be afforded to participants with T2DM or obesity. 
 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 27 
 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• To characterize the extent of excretion of total 
radioactivity in urine, feces, and emesis (if any) 
following administration of a single oral dose of 
[14C]PF-07081532. 
• Total recovery of radioactivity in urine, feces, and 
emesis (if any), and both routes combined, expressed as 
a percent of total oral radioactive dose administered. 
• To characterize the metabolic profile and identify 
circulating and excreted metabolites following 
administration of a single oral dose of 
[14C]PF-07081532. 
• Metabolic profiling/identification and determination of 
relative abundance of [14C]PF-07081532 and the 
metabolites of [14C]PF-07081532 in plasma, urine, and 
feces. 
Secondary: 
Secondary: 
• To quantify plasma PK parameters of PF-07081532 
and total radioactivity following administration of a 
single oral dose of [14C]PF-07081532. 
• AUClast, Cmax, Tmax, and if data permit, AUCinf, t½, CL/F 
(PF-07081532 only), and Vz/F (PF-07081532 only), to 
describe single oral dose PK in Period 1 of: 
• 
Total radioactivity in plasma; 
• 
PF-07081532 in plasma. 
• To quantify plasma PK parameters of 
[14C]PF-07081532, following administration of a 
single, IV, microdose of [14C]PF-07081532. 
• [14C]PF-07081532 parameters to describe IV plasma PK: 
AUClast, AUClast(dn), Cmax, Cmax(dn), Tmax, and if data 
permit, AUCinf, AUCinf(dn), t½, CL, Vss and MRT. 
• To determine the absolute oral bioavailability (F) of 
PF-07081532 following administration of a single oral 
dose of PF-07081532 compared to a single IV 
microdose of [14C]PF-07081532. 
• F computed from plasma AUCinf (if data permit, 
otherwise AUClast) of oral unlabeled PF-07081532 in 
Period 2 and IV microdose of [14C]PF-07081532 in 
Period 2. 
• To determine the fraction of dose absorbed (Fa) 
following administration of a single oral dose of 
[14C]PF-07081532. 
• Fa calculated from ratio of total urinary radioactivity 
following oral administration of [14C]PF-07081532 in 
Period 1 and IV administration of [14C]PF-07081532 in 
Period 2. 
• To evaluate safety and tolerability of PF-07081532, 
administered as a single oral dose of 
[14C]PF-07081532 or a single oral dose of 
PF-07081532 followed by administration of a single 
IV microdose of [14C]PF-07081532. 
• Safety endpoints including physical examinations, 
adverse events, clinical laboratory measurements, vital 
signs, and ECG. 
Tertiary/Exploratory: 
Tertiary/Exploratory: 
• To characterize cumulative rate of excretion of total 
radioactivity in urine and feces over time following 
administration of a single oral dose of 
[14C]PF-07081532. 
• Cumulative recovery of radioactivity in urine and feces, 
and both routes combined over time as a percentage of 
total radioactive dose administered. 
• To quantify plasma PK parameters of PF-07081532, 
following administration of a single oral dose of 
(unlabeled) PF-07081532. 
• Parameters to describe oral plasma PK following oral 
administration of PF-07081532 in Period 2: Cmax, 
Cmax(dn), Tmax, AUClast, AUClast(dn), and if data permit, 
AUCinf, AUCinf(dn), t½, CL/F and Vz/F. 
CCI 
3. OBJECTIVES AND ENDPOINTS 
 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 28 
 
 
4. STUDY DESIGN 
4.1. Overall Design 
C3991006 is a Phase 1, open-label, 2-period, fixed sequence study to characterize the 
metabolic profile and routes of excretion of oral [14C]PF-07081532 and to evaluate the 
absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-07081532 in healthy male 
participants. 
Participants will be screened for enrollment in this study within 28 days of dosing on Day 1 
of Period 1, to confirm that they meet the inclusion/exclusion criteria specified in Section 5. 
The expected duration of participation from screening to follow-up will be approximately 
8 weeks (minimum) to approximately 12 weeks (maximum). The overall study design is 
summarized in Section 1.2 (Schema). 
Regimen in Period 1: An oral dose of 30 mg PF-07081532 containing approximately 
250 nCi [14C] (ie, radiolabeled PF-07081532, [14C]PF-07081532) will be administered within 
approximately 10 minutes of completion of a standard breakfast (see Sections 5.3.2 
and 6.1.1). 
Regimen in Period 2: An oral dose of 30 mg unlabeled PF-07081532 will be administered 
followed at approximate Tmax by an IV dose of 250 nCi [14C] in 100 µg of PF-07081532 
(ie, [14C]PF-07081532). The [14C]PF-07081532 IV dose will be administered as an infusion 
over approximately 15 minutes, starting at approximately 1 hour (Tmax) after the 
administration of the oral unlabeled PF-07081532 dose. Oral unlabeled PF-07081532 will be 
administered within approximately 10 minutes of completion of a standard breakfast (see 
Sections 5.3.2 and 6.1.1). 
In Period 1, a sufficient number of participants will be admitted on Day -1 to the CRU to 
ensure that 6 participants are dosed on Day 1. Any participants who are prematurely 
withdrawn (or offer non-evaluable or partially evaluable data) will be replaced to ensure 
6 evaluable participants completing Period 1. In Period 2, participants who are prematurely 
withdrawn may be replaced at the discretion of sponsor. Further details on “evaluable 
participants” will be provided in the SAP. 
Discharge Criteria 
In Period 1, participants may be discharged from the CRU on or after Day 7 when at least 
1 of the following criteria are met: 
1. ≥90% of radioactive dose has been recovered in urine+feces+emesis (if any); 
2. <1% of radioactive dose has been recovered in urine+feces during 24 hours interval 
over two consecutive days. 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 29 
 
 
However, if neither of these 2 criteria are met and the participant has reached Day 21 in 
Period 1 they may be discharged prior to Period 2, or they may remain in the CRU until 
initiation of Period 2. If Period 1, Day 21 falls on the same day as Period 2, Day -1, for 
participants who have not been discharged from the CRU: 
• Physical examination will not be performed on Period 1, Day 21. 
• ECG and vital signs assessments will not be performed on Period 1, Day 21. 
• Clinical laboratory (blood) and spot urine collection for urinalysis (and microscopy, if 
needed) assessments will be performed on Period 1, Day 21 and will serve as the 
Day -1 assessments of Period 2. 
• The last urine sample for total radioactivity and metabolite ID collected up to 
24 hours before dosing in Period 2 (ie, Period 1, Day 21) will serve as the Day -1 
assessment of Period 2. 
• The last fecal sample for total radioactivity and metabolite ID collected up to 
48 hours before dosing in Period 2 (ie Period 1, Day 21 or Period 1, Day 20 if no 
bowel movement on Day 21) will serve as the Day -1 assessment of Period 2. 
In Period 2, participants will be discharged from the CRU on Day 7. 
At least 21 days of washout is required between dosing in Period 1 and Period 2. The 
participants may stay at the CRU during the washout period at the discretion of the 
investigator. Participants will have 1 follow-up contact (may be a phone call) that will occur 
at least 28 days and up to 35 days following the last dose of study intervention in Period 2. 
4.2. Scientific Rationale for Study Design 
A fixed sequence, open-label, study design has been chosen to minimize intra-individual 
variability and enable within-participant comparison of the urinary excretion of radioactivity 
with both oral and IV routes for the estimation of Fa. As is common for Phase 1 studies, the 
population envisioned for this study is healthy participants. Only males will be included in 
this study given the desire to enroll a homogeneous population due to the small sample size 
of this study. 
Available PK data with PF-07081532 administered under fasted or fed conditions indicate 
that PF-07081532 may be administered without regard to food. In this study, dosing of 
PF-07081532 is planned to occur in the fed state, with standard breakfast in both periods, as 
described in Section 5.3.2, to reflect the conditions for anticipated use of PF-07081532 in 
future trials and the target patient population. 
In this study, a “microtracer” approach will be used where the [14C] dose is much lower than 
in conventional ADME studies. With this approach, [14C] will be quantified using an AMS 
detection technique. This technology allows ADME studies to be conducted without WBA 
data, as concentrations of [14C] and resulting exposures are so minute that dosimetry 
calculations are not needed. 


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Period 1 of the study is designed to evaluate the metabolic fate and extent of excretion of 
PF-07081532 following 30 mg dose (250 nCi) via the intended clinical route of 
administration (oral) of [14C]PF-07081532. In order to assess the metabolic fate of 
[14C]PF-07081532, metabolites of [14C]PF-07081532 circulating in plasma and eliminated in 
urine and feces following oral administration will be determined using AMS and 
UPLC-HRMS. Additionally, extent of excretion will be determined by recovery of total 
radioactivity excreted in urine and feces. Lastly, plasma PK of PF-07081532 will be 
compared to total radioactivity PK as an additional way to quantify circulating metabolites. 
Based on the half-life observed after single dose administration in Study C3991001 (mean 
ranging between 18 and 21 hours with individual values up to 29 hours), PF-07081532 is 
expected to be eliminated from plasma by Day 7 (144 hours). Additional 14 days of 
permitted extended stay in Period 1 (up to Day 21), based on predefined discharging criteria 
(see Section 4.1), is expected to be adequate to enable almost complete recovery of 
radioactivity in excreta and allow excretion of any potential metabolites with longer 
half-lives. 
Samples for measurement of radioactivity in CCI 
 will be collected in Period 1 at 
timepoints specified in the SoA. These samples may be assayed at sponsor’s discretion to 
support any potential investigations in case of less than expected recovery of total 
radioactivity via urine and feces. Results from the analysis of these samples, if performed, 
may not be included in the CSR. 
Period 2 of the study is designed to evaluate F and also allow to estimate Fa of the oral 
PF-07081532 dose. Determination of the Fa will provide information on the total 
PF-07081532 dose absorbed, regardless of the fate of that dose after absorption 
(eg, metabolism, degradation). Since F is dependent on Fa, Fg and Fh, characterization of both 
F and Fa will also enable determination of the first pass effect. A microdose (100 µg 
[250 nCi]) of [14C]PF-07081532 will be administered as an IV infusion starting at the 
approximate Tmax (1 hour) following an oral 30 mg dose of unlabeled PF-07081532. 
[14C]PF-07081532 in plasma will be assessed via AMS following chromatographic 
separation. F will be calculated as the ratio of dose-normalized plasma AUCinf following 
orally administered PF-07081532 to dose-normalized plasma AUCinf following IV 
administered [14C]PF-07081532. Administration of the IV microdose approximately at the 
Tmax of the oral dose assures the presence of the appropriate total mass of drug material in the 
body so that PK data from the microdose (100 µg) can be scaled up to those measured 
following the higher oral dose (30 mg). 
In Period 2, urine samples will be collected at prespecified intervals as described in the SoA 
and total radioactivity excreted in urine following IV administered [14C]PF-07081532, will 
be measured via AMS. The ratio of dose-normalized total radioactivity recovered in urine 
following oral administration of [14C]PF-07081532 in Period 1 to that recovered in urine 
following IV [14C]PF-07081532 in Period 2 will provide an estimate of the Fa following oral 
administration. This Fa assessment assumes that the distribution, metabolism and excretion 
properties of PF-07081532 remain unchanged by the route of administration (oral or IV). 
Participants will be discharged from the CRU on Day 7 of Period 2, which is considered 


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adequate to meet study objectives and ensure that PF-07081532 has been eliminated from 
plasma. Even in the case that urine radioactivity recovery is not complete by Day 7 in 
Period 2 (after IV administration), it is expected that comparison with the urine radioactivity 
collected in Period 1 (after oral administration) over the same period of time (up to Day 7) 
will provide an adequate estimate of Fa. 
Given that biliary and/or intestinal excretion is not expected to be a major clearance pathway 
of PF-07081532, feces in Period 2 will be collected but will be assayed at sponsor’s 
discretion (if emerging data from the study indicate that contrary to current expectations, 
biliary and/or intestinal excretion may be a major clearance pathway or if for any other 
reason the study team determines that analysis of feces from Period 2 would further inform 
disposition of PF-07081532 in humans). Results from such analyses may or may not be 
included in the CSR, and should be interpreted with caution given that this study is not 
designed to achieve complete recovery of radioactivity in Period 2. 
To aid in the future development of a potential pediatric dosage form of PF-07081532, the 
current study will assess the bitterness, tongue/mouth burn, and throat burn of the liquid 
formulation immediately after (within 3 minutes) and over 20 minutes post oral dose 
administration of [14C]PF-07081532, in Period 1 only. 
4.2.1. Choice of Contraception/Barrier Requirements 
The potential risk of exposure to PF-07081532 in a sexual partner of a male participant in 
this study via ejaculate is low, and therefore no contraception (condom) use in male 
participants is warranted. The calculated safety margin is ≥100-fold between the estimated 
partner exposure due to seminal transfer and the NOAEL for serious manifestations of 
developmental toxicity in nonclinical studies. The safety margin of 100-fold is based on 
applying a 10-fold safety factor for interspecies extrapolation and a 10-fold safety factor for 
susceptible populations (See Appendix 4).6 
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 
In C3991006, each participant will be exposed to approximately 500 nCi over the entire 
study duration, which includes dosing [14C]PF-07081532 in Period 1 and Period 2. This is 
classed as a microtracer dose and based on precedent,7,8 the doses of radioactivity used in this 
study are expected to result in adequate sensitivity for AMS quantification. 
In Period 1, a single, oral dose of 30 mg of [14C]PF-07081532 (250 nCi), will be 
administered. In Study C3991001, single ascending doses up to 200 mg were tested and were 
considered safe and had a tolerability profile in line with expectations for the mechanism of 
action, with the majority of AEs being mild in severity and in the Gastrointestinal Disorders 
SOC (with nausea and vomiting the most frequently observed). In that study, a single dose of 


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30 mg was very well tolerated with an AE profile that did not differ from placebo and with 
no treated participants experiencing vomiting up to that dose level (however, vomiting was 
observed at the 100 mg and 200 mg dose levels). Therefore, given the desire to minimize the 
risk of emesis in this study, a dose of 30 mg is considered appropriate. Given the early stage 
of development, there is still uncertainty around the efficacious dose range of PF-07081532 
(doses spanning from 20 mg to 260 mg BID are currently planned to be investigated in Phase 
2 efficacy studies). Since dose-proportional increases in exposure (AUC) of PF-07081532 
have been observed after single dose (from 30 mg to 200 mg) and after multiple dose (from 
10 mg to 180 mg QD), the results from this study can be extrapolated to doses exceeding 
30 mg. 
In Period 2, a single oral unlabeled 30 mg dose of PF-07081532 will be administered with 
food (standard breakfast), followed by an IV microdose of [14C]PF-07081532, 100 µg 
(250 nCi) administered as infusion starting at the approximately expected Tmax (1 hour) of the 
unlabeled oral dose. The IV microdose of 100 µg is ~0.3% of the oral dose of 30 mg and 
therefore expected to have negligible effect on the plasma PK of unlabeled PF-07081532, 
allowing for appropriate estimation of bioavailability. As per the ICH M3 (R2),5 human 
administration of an IV microdose of up to 100 µg can be supported with nonclinical 
toxicology studies where the drug is administered orally and without the need for additional 
nonclinical toxicology studies via IV route of administration. 
4.4. End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study 
or last scheduled procedure shown in the SoA for the last participant in the trial globally. 
A participant is considered to have completed the study if they have completed all periods 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 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age and Sex: 
1. Male participants must be 18 to 60 years of age, inclusive, at the time of signing the 
ICD. 


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• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) 
participants. 
2. Male participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, blood pressure and pulse rate 
measurement, standard 12-lead ECG, and laboratory tests. 
Other Inclusion Criteria: 
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). 
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures including 
collection of blank urine and feces samples prior to dosing on Day 1, Period 1. 
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements listed in the ICD and in this protocol. 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions: 
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing). 
• Any condition possibly affecting drug absorption (eg, gastrectomy, 
cholecystectomy). 
• Positive testing at screening for HIV, HBsAg, HBcAb, HBsAb or HCVAb. Note: 
A positive HBsAb due to hepatitis B vaccination is permissible. 
2. Personal or family history of MTC or MEN2, or participants with suspected MTC per 
the investigator’s judgement. 
3. History of irregular bowel movements (eg, irritable bowel syndrome, frequent 
episodes of diarrhea, or constipation defined by less than 1 bowel movement on 
average per 2 days) or lactose intolerance. 
4. Other medical or psychiatric condition including recent (within the past year of 
screening) or active suicidal ideation/behavior or laboratory abnormality or other 
conditions or situations related to COVID-19 pandemic (eg, contact with positive 
case) that may increase the risk of study participation or, in the investigator’s 
judgment, make the participant inappropriate for the study. 


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Prior/Concomitant Therapy: 
5. Use of any prescription or non-prescription drugs and dietary and herbal supplements 
as outlined in Section 6.9 and Appendix 10. 
Prior/Concurrent Clinical Study Experience: 
6. Previous administration with an investigational product (drug or vaccine) within 
90 days (or as determined by the local requirement) preceding the first dose of study 
intervention used in this study. 
7. Known prior participation (ie, received at least 1 dose of study intervention) in a 
study involving PF-07081532 or known intolerance to a GLP-1R agonist. 
Diagnostic Assessments: 
8. A positive urine drug test at screening or admission. 
9. 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. 
10. eGFR <90 mL/min/1.73m2 (calculated with the 2021 CKD-EPI Scr only equation) at 
screening. 
11. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTcF >450 ms, 
complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T 
interval changes suggestive of myocardial ischemia, second- or third- degree AV 
block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT 
interval is >450 ms, this interval should be rate-corrected using the Fridericia method 
only and the resulting QTcF should be used for decision making and reporting. If 
QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice 
and the average of the 3 QTcF or QRS values used to determine the participant’s 
eligibility. Computer-interpreted ECGs should be overread by a physician 
experienced in reading ECGs before excluding a participant. 
12. 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 ≥1.5 × ULN; 


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• 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. 
Other Exclusion Criteria: 
13. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 
5 (male) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake 
should not exceed 14 units per week (1 unit = 8 ounces [240 mL] beer, 1 ounce 
[30 mL] of 40% spirit, or 3 ounces [90 mL] of wine). 
14. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
15. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is planned to flush IV catheters. 
16. Total [14C] radioactivity measured in plasma at screening exceeding 11 mBq/mL. 
17. Participants with current use of tobacco- and/or nicotine-containing products 
exceeding equivalent of 5 cigarettes per day. 
18. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members. 
5.3. Lifestyle Considerations 
The following guidelines are provided: 
5.3.1. Contraception 
No contraception methods are required by the sponsor for male participants receiving 
PF-07081532. Please refer to Section 4.2.1 and Appendix 4. 
5.3.2. Meals and Dietary Restrictions 
While inpatient, the meals consumed are expected to follow the restrictions outlined below: 
• Participants must abstain from all food and drinks (except water) for at least 4 hours 
prior to any scheduled safety laboratory evaluations. 
• Noncaffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices—see 
below) may be consumed with meals and the evening snack. 


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Dose administered with food, on Day 1 of Period 1 and Period 2: 
• Following an overnight fast (abstain from all food and drink, except water) of at least 
8 hours, prior to predose PK sample collection, a standard breakfast will be served. 
• Participants should begin breakfast approximately 30 minutes prior to oral 
PF-07081532 administration. The breakfast will be consumed over approximately a 
20 minute period with the study intervention administered approximately 10 minutes 
after completion of the meal. Participants will be encouraged to complete the entire 
breakfast. 
On Day 1 of study Period 1 and Period 2, the same breakfast, including food and 
beverage, should be served. Water may be consumed without restriction. 
• On Day 1 of both the study periods, lunch will be provided approximately 4 hours 
after oral administration of PF-07081532. Dinner will be provided approximately 
10 hours after oral administration of PF-07081532. An evening snack may be 
permitted. If judged necessary by the investigator, participants may delay or skip a 
post-dose meal (lunch, dinner or snack) on dosing Day 1 in case of a gastrointestinal 
AE. 
• Participants will refrain from consuming red wine, grapefruit or grapefruit-related 
citrus fruits (eg, Seville oranges, pomelos) and their juices from 7 days prior to the 
first dose of study intervention until collection of the final PK blood sample. 
• While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein. The daily caloric intake 
per participant should not exceed approximately 3200 kcal. 
• The nutritional macronutrient composition consumed by each participant should be 
maintained, as much as practically possible, during the inpatient stay. 
• Ingestion of indigestible foods (eg, corn, nuts) should be avoided for 2 days prior to 
dosing and while inpatient to aid fecal homogenization. 
• When a meal is scheduled at the same time as an ECG and/or vital sign assessments, 
the meal will be provided after the ECG and/or vital sign assessments are completed. 
5.3.2.1. Dietary Fiber Supplementation 
To help assure regularity in bowel movements, nutritional composition should include high 
fiber content (at least 15 g of fiber per 1000 kcal). This may include consumption of fiber 
(eg, capsules), at a frequency dictated by the investigator, starting with the evening meal 
(ie, approximately 10 hours post dose) on Day 1, for duration of inpatient stay to ensure at 
least 1 bowel movement per day. 


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If an individual participant has not experienced a bowel movement in the first 24 hours after 
dosing, water intake should be increased and prune juice should be offered during Day 2. 
Despite these measures, if bowel movement does not occur, on Day 3 and each subsequent 
day, consideration should be given to administration of a mild laxative/stool softener 
(eg, milk of magnesia, docusate), at investigator’s discretion. 
5.3.3. 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. 
• 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 urine alcohol 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. 
5.3.4. Activity 
• Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 96 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, pulse rate, and 
ECG measurements), eating, and drinking beverages other than water during the first 
4 hours after dosing. 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. Screen failure data are collected and remain as 
source and are not reported on the CRF. 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
not be rescreened. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study interventions are all prespecified investigational products, medical devices, and other 
interventions (eg, surgical and behavioral) intended to be administered to the study 
participants during the study conduct. 


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For the purposes of this protocol, study intervention refers to PF-07081532 (either unlabeled 
or [14C]PF-07081532). 
6.1. Study Intervention(s) Administered 
Study Intervention(s) 
Intervention Name 
[14C]PF-07081532 
PF-07081532 
[14C]PF-07081532 
Arm Name 
(group of 
participants 
receiving a specific 
treatment or no 
treatment) 
Period 1 
Period 2 
Period 2 
Type 
Drug 
Drug 
Drug 
Dose Formulation 
Extemporaneously prepared 
liquid formulation 
Extemporaneously 
prepared liquid 
formulation 
Extemporaneously prepared 
liquid formulation 
Unit Dose Strength(s) 
NA 
NA 
NA 
Dosage Level(s) 
30 mg, single dose 
30 mg, single dose 
100 µg, single dose 
Route(s) of 
Administration 
Oral 
Oral 
IV infusion 
Use 
Experimental 
Experimental 
Experimental 
IMP or NIMP/AxMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally by the 
sponsor. Refer to the SAI 
Provided centrally by the 
sponsor. Refer to the SAI 
Provided centrally by the 
sponsor. Refer to the SAI 
Packaging and 
Labeling 
[14C]PF-07081532 components 
will be supplied by Pfizer, as 
bulk API and, where necessary, 
bulk excipients for the 
manufacture of the [14C] 
labeled oral liquid formulation 
Unlabeled PF-07081532 
will be provided by 
Pfizer as bulk powders 
for extemporaneous 
preparation 
[14C]PF-07081532 components 
will be supplied by Pfizer, as 
bulk API and, where necessary, 
bulk excipients for the 
manufacture of the [14C] 
labeled IV liquid formulation 
Current/Former 
Name(s) or Alias(es) 
[14C]PF-07081532 
PF-07081532 
[14C]PF-07081532 
Study Arm(s) 
Arm Title 
Period 1 
Period 2 
Arm Type 
Experimental 
Experimental 
Arm Description 
Oral dose of 30 mg PF-07081532 
containing 250 nCi [14C] 
([14C]PF-07081532) will be 
administered as an 
extemporaneously prepared liquid 
formulation, approximately 
10 minutes after completion of 
breakfast 
Unlabeled oral dose of PF-07081532, 30 mg will 
be administered as an extemporaneously prepared 
liquid formulation, approximately 10 minutes 
after completion of breakfast. Approximately 
1 hour after the administration of the unlabeled 
oral dose, a single dose of 100 µg PF-07081532 
containing 250 nCi [14C] ([14C]PF-07081532) will 
be administered IV, as an infusion over 
approximately 15 minutes 
Associated Intervention 
Labels 
[14C]PF-07081532 
PF-07081532, [14C]PF-07081532 


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6.1.1. Administration 
In both periods, study intervention will be administered following breakfast, as described in 
Section 5.3.2, and according to the SAI. 
In Period 1, oral dose of [14C]PF-07081532, 30 mg (250 nCi) will be administered as an 
extemporaneously prepared liquid formulation, approximately 10 minutes after completion of 
breakfast. 
In Period 2, unlabeled oral dose of PF-07081532, 30 mg will be administered as an 
extemporaneously prepared liquid formulation, approximately 10 minutes after completion of 
breakfast. Approximately 1 hour after the administration of the unlabeled oral dose, a single 
dose of [14C]PF-07081532, 100 µg (250 nCi) will be administered IV, as an infusion over 
approximately 15 minutes. 
Administration of labeled and unlabeled PF-07081532 via oral and IV dosing routes will be 
performed by qualified investigator site personnel (in accordance with local regulations and 
laws). Please refer to the SAI for further details. 
6.2. Preparation, Handling, Storage, and Accountability 
1. The investigator or designee must confirm that appropriate conditions 
(eg, temperature) have been maintained during transit for all study interventions 
received and any discrepancies are reported and resolved before use of the study 
intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention. 
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized site staff. At 
a minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented upon 
return to business. 
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to the labeled storage conditions, 
as soon as possible. Once an excursion is identified, the study intervention must be 
quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the excursion definition and information to 
report for each excursion will be provided to the site by the sponsor. 
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label. 


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6. Study interventions should be stored in their original containers. 
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records). 
8. Further guidance and information for the final disposition of unused study 
interventions are provided by the sponsor. 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. 
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. 
Unlabeled PF-07081532 and [14C]PF-07081532 oral dosing formulations will be prepared in 
the CRU by 2 trained personnel and QP. Details of dose preparation will be given in a 
separate EDR. The prepared doses will be provided in unit dose containers and labeled in 
accordance with Pfizer regulations and the investigator site’s labeling requirements. 
[14C]PF-07081532 formulation for IV administration will be manufactured at the CRU by 
2 trained personnel and QP-released prior to administration. Details of the dose preparation 
will be provided in a separate TA. The prepared doses will be provided in unit dose 
containers and labeled in accordance with Pfizer regulations and the investigator site’s 
labeling requirements. 
6.3. Assignment to Study Intervention 
Following completion of informed consent at the screening visit, each participant will be 
assigned an 8-digit SSID number, by the site staff. The first 4 digits of the SSID will reflect 
the sponsor-assigned site number and the remaining 4 digits will reflect each participant’s 
unique number assigned in chronological order as informed consent is obtained. In addition, 
on Day 1, each participant who is dosed with the study intervention will be assigned a 
separate, distinct number (as provided to the site by the sponsor at the start of the study) to 
enable execution of sponsors’ standard processes for analysis of all PK-related samples. 


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6.4. Blinding 
This is an open-label study. 
6.4.1. Blinding of Participants 
Participants will be unblinded to their assigned study intervention. 
6.4.2. Blinding of Site Personnel 
Investigators and other site staff will be unblinded to participants’ assigned study 
intervention. 
6.4.3. Blinding of the Sponsor 
Sponsor staff will be unblinded to participants’ assigned study intervention. 
6.5. Study Intervention Compliance 
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second qualified member of the study site staff. 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. Study site personnel will examine each participant’s mouth to ensure that 
the oral dose of study intervention was ingested. 
See the site administration instructions for instructions on how to prepare the study 
intervention for administration. Study intervention should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance. 
6.6. Dose Modification 
Dose modification of PF-07081532 is not permitted. 
6.7. Continued Access to Study Intervention After the End of the Study 
No study intervention will be provided to participants at the end of their study participation. 
6.8. Treatment of Overdose 
For this study, any dose of PF-07081532 greater than 1.6 g within a 24-hour time period is 
projected to result in exposure that will exceed that observed at the NOAEL in the pivotal 
9-month toxicology study in monkeys, after accounting for species difference in plasma 
protein binding, and thus will be considered an overdose. 


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There is no specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should: 
1. Contact the study medical monitor within 24 hours. 
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up. 
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 3 days from the date of the last dose of 
study intervention if requested by the study medical monitor (determined on a 
case-by-case basis). 
6.9. Prior and Concomitant Therapy 
Use of any prescription or non-prescription 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 or as outlined in Appendix 10 specifically for medications prohibited due to 
potential DDI. Participants will abstain from all concomitant treatments during the study, 
except for the treatment of AEs. Limited use of non-prescription 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 and as long as they are not listed in 
Appendix 10. Use of dietary fiber supplementation, prune juice or non-prescription 
medications (eg, milk of magnesia, ducosate) specifically used as needed to promote bowel 
movement (see Section 5.3.2.1) is allowed at investigator’s discretion and such use should be 
recorded. Acetaminophen/paracetamol may also be used at doses of ≤1 g/day. 
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. 
6.9.1. Rescue Medicine 
There is no rescue therapy to reverse AEs observed with PF-07081532; standard medical 
supportive care must be provided to manage any AEs. 


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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: safety, behavioral, 
compliance, or administrative reasons, or if the study is terminated by sponsor. 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant should 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. 
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 their own request. Reasons for 
discontinuation from the study include the following: safety, behavioral, compliance or 
administrative reasons, or if the study is 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 and then are 
prematurely withdrawn from the study. Participants should be questioned regarding their 
reason for withdrawal. 
The participant will be permanently discontinued from the study intervention and the study at 
that time. 
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 


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7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
the participant is alive or dead) is being measured, publicly available information should be 
used to determine vital status only as appropriately directed in accordance with local law. 
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to attend a required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study; 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record; 
• Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES 
8.1. Administrative Procedures 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 


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All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria. 
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 make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner. 
ECGs and vital sign assessments (pulse rate and BP) should be collected prior to any blood 
draw. 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 
500 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 56 consecutive 
days. 
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol. 
8.2. Efficacy Assessments 
Not applicable. 
8.3. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety 
measurements may be obtained at any time during the study to assess any perceived safety 
issues. 


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8.3.1. Physical Examinations 
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, 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 8.4.1 to 8.4.3. 
8.3.2. Vital Signs 
8.3.2.1. Blood Pressure and Pulse Rate 
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. BP should not be taken 
from the arm with an IV infusion. 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. 
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3. 


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8.3.3. 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 HR and measures PR interval, QT interval, QTcF, 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 from the current period to baseline measurements. Additional ECG monitoring 
will occur if a) a postdose QTcF interval is increased by ≥60 ms from the baseline and is 
>450 ms; or b) an absolute QT value is ≥500 ms for any scheduled ECG. If either of these 
conditions occurs, then 2 additional ECGs will be collected approximately 2 to 4 minutes 
apart to confirm the original measurement. If the QTcF values from these repeated ECGs 
remain above the threshold value, then a single ECG must be repeated at least hourly until 
QTc values from 2 successive ECGs fall below the threshold value that triggered the repeat 
measurement. 
If a) a postdose QTcF interval remains ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG for greater than 4 hours (or sooner, at 
the discretion of the investigator); or c) QTcF value get progressively longer, the participant 
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTcF 
values do not return to less than the criteria listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator). 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range. 
ECG values of potential clinical concern are listed in Appendix 8. 
8.3.4. 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. 


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The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition. 
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within 5 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or study medical monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
DILI. 
See Appendix 7 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities. 
Participants may undergo random urine drug testing at the discretion of the investigator. 
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.3.5. COVID-19 Specific Assessments 
Assessment of risk for, symptoms of or testing for COVID-19 may be performed at 
screening, admission to the CRU and/or at other times during the study at investigator 
discretion and according to local site policies. 
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of an AE and an SAE can be found in Appendix 3. 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner. 


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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
8.4.1. Time Period and Frequency for Collecting AE and SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before undergoing any study-related procedure and/or receiving study 
intervention), through and including a minimum of 28 calendar days, except as indicated 
below, after the last administration of the study intervention. 
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator. 
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment. 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 
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 they consider 
the event to be reasonably related to the study intervention, the investigator must promptly 
report the SAE to Pfizer using the CT SAE Report Form. 
8.4.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available. 
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF 
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF. 


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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. 
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4. 
8.4.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.4.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3. 
8.4.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators. 


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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. 
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure, occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure. 
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness. 
8.4.5.1. Exposure During Pregnancy 
An EDP occurs if: 
• A male participant who is receiving or has discontinued study intervention 
inseminates a female partner. 
• A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP: 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion. 
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’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. 


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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 should be reported 
as an SAE; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.4.5.2. Exposure During Breastfeeding 
An EDB occurs if: 
• A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion. 
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When EDB occurs in the setting of environmental exposure, 


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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 EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB. 
8.4.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the CT SAE Report Form regardless of 
whether there is an associated SAE. Since the information about the occupational exposure 
does not pertain to a participant enrolled in the study, the information is not recorded on a 
CRF; however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file. 
8.4.6. Cardiovascular and Death Events 
Not applicable. 
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.4.8. Adverse Events of Special Interest 
Not applicable. 
8.4.8.1. Lack of Efficacy 
This section is not applicable because efficacy is not expected in the study population. 
8.4.9. Medical Device Deficiencies 
Not applicable. 
8.4.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. 


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Medication errors are recorded and reported as follows: 
 
Recorded on the 
Medication Error Page 
of the CRF 
Recorded on the 
Adverse Event Page 
of the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
All (regardless of whether 
associated with an AE) 
Any AE or SAE associated 
with the medication error 
Only if associated with an 
SAE 
Medication errors include: 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant. 
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. 
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. 
In the event of a medication dosing error, the sponsor should be notified within 24 hours. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
8.5. Pharmacokinetics 
Instructions for the collection and handling of biological samples (plasma, urine, fecal, 
emesis [if any], and CCI 
) will be provided in the laboratory manual or by the sponsor. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. The blood samples collected at nominal time point of 
10 minutes and 15 minutes post start of IV infusion, will not be considered as a PD if it is 
collected within ±2 minutes of nominal time post start of infusion. Note: The 15-minute 
sample should not be collected prior to end of infusion. Collection of samples more than 
10 hours after dose administration that are obtained ≤1 hour away from the nominal time 
relative to dosing will not be captured as a protocol deviation, as long as the exact time of the 
collection is noted on the source document and the CRF. 


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Samples collected for analyses of PK, radioactivity and/or metabolite profiling 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, or for other 
internal exploratory purposes. 
Genetic analyses will not be performed on these samples unless consent for this was included 
in the informed consent. Participant confidentiality will be maintained. 
Samples must be processed and shipped as indicated in the instructions provided to the 
investigator site to maintain sample integrity. Any deviations from the 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. 
8.5.1. Analysis of Plasma 
8.5.1.1. Period 1 Plasma Analysis of PF-07081532 Using LC/MS/MS 
During Period 1, at each specified time-point in the SoA, blood samples (3 mL for 
LC/MS/MS analysis of PF-07081532) to provide approximately 1.2 mL plasma will be 
collected into appropriately labeled tubes containing K2EDTA. 
Samples for unlabeled PF-07081532 will be analyzed using a validated LC/MS/MS method 
in compliance with Pfizer standard operating procedures. 
8.5.1.2. Period 1 Plasma Analysis of Total Radioactivity [14C] Using AMS 
During Period 1, at each specified time-point in the SoA, blood samples (4 mL for total 
radioactivity [14C]) to provide approximately 1.6 mL plasma will be collected into 
appropriately labeled tubes containing K2EDTA. For the pre-dose sample only, the blood 
volume collected is 10 mL. 
8.5.1.3. Period 1 Plasma Analysis for Metabolite Profiling Using AMS and 
UPLC-HRMS 
During Period 1, at each specified time-point in the SoA, blood samples (10 mL for 
metabolite identification) to provide approximately 4 mL plasma will be collected into 
appropriately labeled tubes containing K2EDTA. 
Plasma samples in Period 1 will be analyzed using AMS and UPLC-HRMS, and will 
provide metabolite profile of [14C]PF-07081532. Samples collected for plasma analysis of 
total [14C] or PF-07081532 may also be analyzed for metabolite profiling at the discretion of 
the sponsor. 


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8.5.1.4. Period 2 Plasma for Analysis of Oral, Unlabeled PF-07081532, Using 
LC/MS/MS 
For Period 2, blood samples (3 mL) to provide approximately 1.2 mL plasma for 
concentrations of unlabeled PF-07081532 will be collected into appropriately labeled tubes 
containing K2EDTA at times specified in the SoA. 
Samples for unlabeled PF-07081532 will be analyzed using a validated LC/MS/MS 
analytical method in compliance with Pfizer standard operating procedures. 
8.5.1.5. Period 2 Plasma for Analysis of IV [14C]PF-07081532 Using AMS and 
UPLC-HRMS 
During study Period 2, blood samples (4 mL) to provide approximately 1.6 mL plasma will 
be collected as specified in the SoA following IV administration of [14C]PF-07081532, into 
appropriately labeled tubes containing K2EDTA. Samples from Period 2 will be analyzed for 
[14C]PF-07081532 using a validated quantitative AMS method following chromatographic 
separation of the parent drug. 
8.5.2. Analysis of Urine 
In Period 1 and Period 2, urine will be collected at time intervals specified in SoA (Table 1 
and Table 2 respectively) to analyze the amount of total radioactivity eliminated in urine 
following oral and IV administration of [14C]PF-07081532, respectively. Additionally, urine 
from Period 1 will be assessed for metabolite identification following oral administration of 
[14C]PF-07081532. 
• Prior to dosing on Day 1 (within 24 h), each participant must empty his urinary 
bladder; an aliquot from this urine will serve as the “urine blank”. 
• Following dosing on Day 1, each void post dose will be collected and saved in a 
container and stored in refrigerated conditions (ie, 2-8°C) for the duration of the 
collection interval. Urine collection timings should be recorded in the CRF. 
• At the end of the collection interval, participants must complete a forced void, with 
this void included as part of the interval collection. 
• If the end of urine collection interval coincides with a meal, participants will be asked 
to complete the forced void prior to initiation of the meal; in such cases, so long as 
the actual time of forced void is recorded, for practical reasons, the fact that this 
collection may be more than 30 minutes (and up to 45 minutes) prior to end of 
collection interval is acceptable and will not be considered as protocol deviation. 
• At the end of each urine collection interval, the urine container will be mixed 
thoroughly and the total weight of urine collected during the interval will be 
measured and recorded. All urine aliquots should be collected using a new pipette 
tube for each participant at each time point. All urine samples within each collection 


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interval will be mixed thoroughly before aliquoting. The details regarding the 
collection (eg, aliquots volume), processing, storage and shipping of the urine 
samples will be provided in the laboratory manual. Following completion of 
radioanalysis and sub-sample collections for metabolite profiling, the remaining 
aliquoted urine samples will be discarded upon approval from the sponsor. 
8.5.3. Analysis of Feces 
Feces will be collected in Period 1 and Period 2 at intervals specified in the SoA (Table 1 
and Table 2 respectively). Feces collected in Period 1 will be analyzed for total [14C] and 
assessed for identification of metabolites at intervals prespecified in the SoA. Fecal samples 
in Period 2 may be analyzed for total [14C] and/or [14C]PF-07081532 and may be assessed for 
identification of metabolites if the study team determines that such analyses would further 
inform disposition of PF-07081532 in humans (see Section 4.2). 
A pre-dose fecal sample is required within 48 hours prior to dosing [14C]PF-07081532 in 
Period 1 and Period 2. If multiple baseline fecal samples are collected for a participant, the 
one closest to dosing will be used as the baseline sample and all other samples will be 
discarded. Total fecal mass is to be recorded for each collection interval. Time and date of 
each bowel movement must be recorded. Additionally, all toilet paper that comes in contact 
with the participant’s feces should also be collected in separate containers from the fecal 
samples for possible analysis. Fecal voids as per SoA will be collected and labeled at the 
clinic and immediately frozen at approximately -20°C. Fecal samples collected at home 
(pre-dose) will be labeled and stored at -20°C after participant enters the clinic. 
In the event of diarrhea during the study, all diarrhea, including any swabbing and 
contaminated linen, should be collected, labeled, and stored in appropriate containers 
at -20°C for possible analysis of radioactivity. Following completion of radioanalysis and 
subsample collections for metabolite profiling, the remaining bulk fecal homogenate will be 
discarded upon approval from the sponsor. 
8.5.4. Emesis Collection 
If emesis occurs within 24 hours after oral administration of [14C]PF-07081532 (Period 1 
only), then the vomitus must be collected and stored for radioactivity assessment. All emesis 
including any swabbing, contaminated linens and facial tissues used to collect bodily 
discharge eg, nose bleeding clean-up tissue and any emesis related clean-up is to be collected 
and stored in a labeled emesis container at 4°C for possible analysis of radioactivity. 
 


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8.5.6. Analysis of Dosing Formulation and Determination of Administered Dose 
Detailed storage and shipment procedures will be provided in the SAI and laboratory manual 
to the clinical site prior to the start of the clinical trial. 
For IV administration of [14C]PF-07081532, the dose volume administered to individual 
participants will be controlled using pre-calibrated infusion pumps. Volume of IV dose 
(computed using weight of the dosing solution administered and the density of the dosing 
solutions), and concentration of PF-07081532 and radioactivity in dosing solution will be 
used to determine the exact dose administered for each participant. 
The actual doses administered will be recorded in the CRF and will be used for calculating 
PK parameters as described in Section 8.10. 
Details on administration of dose and amount of doses administered in Period 1 and Period 2 
will be described in the SAI and the laboratory manual. 
8.6. Genetics 
 
8.7. Biomarkers 
Biomarkers are not evaluated in this study. 
8.8. Immunogenicity Assessments 
Immunogenicity assessments are not included in this study. 
8.9. Health Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 


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9. STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment. 
9.1. Statistical Hypothesis 
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 
Enrolled 
“Enrolled” means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process and 
assignment to and dosing with study intervention. 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. 
Safety analysis set 
All participants assigned to study intervention and who take at 
least 1 dose of study intervention. 
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Participant Analysis 
Set 
Description 
Extent of excretion 
analysis set 
In Period 1, extent of excretion population will be defined by 
evaluable participants who have received 1 dose of 
[14C]PF-07081532 and who have complete total radioactivity 
concentration (urinary and fecal) data and who had no protocol 
deviations that may have affected the extent of excretion analysis. 
Further details will be provided in the SAP, where, notably, 
vomiting within 24 hours post oral dose does not necessarily 
preclude participants as non-evaluable. 
PK concentration set 
The PK concentration population for PF-07081532 is defined as 
all participants dosed with PF-07081532 or [14C]PF-07081532, 
who have at least one PF-07081532 concentration. 
The PK concentration population for [14C]PF-07081532 is 
defined as all participants dosed with [14C]PF-07081532, who 
have at least one [14C]PF-07081532 measurement. 
The PK concentration population for total [14C] is defined as all 
participants dosed with [14C]PF-07081532, who have at least one 
total [14C] measurement. 
PK parameter set 
The PK parameter analysis population for PF-07081532 is 
defined as all participants dosed with PF-07081532 or 
[14C]PF-07081532 who have at least one of the PF-07081532 PK 
parameters of interest. 
The PK parameter analysis population for [14C]PF-07081532 is 
defined as all participants dosed with [14C]PF-07081532 who 
have at least one of the [14C]PF-07081532 PK parameters of 
interest. 
The PK parameter analysis population for total [14C] is defined as 
all participants dosed with [14C]PF-07081532 who have at least 
one of the total [14C] PK parameters of interest. 
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. 
9.3.1. General Considerations 
This section will be described in detail in the SAP. 


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9.3.2. Primary Endpoint(s) Analysis 
9.3.2.1. Extent of Excretion (Period 1) 
Radioactivity excreted in urine and/or feces will be reported as the percentage of the 
administered radioactivity excreted at each time interval, cumulatively through that interval 
and the total percent of dose recovered in urine, feces, and/or emesis (if any). 
Percent recovery and cumulative recovery of total radioactivity in urine, feces and emesis (if 
any) will be determined based on total administered dose. 
Note: While the total percentage of dose excreted is the primary endpoint, the percentage of 
the administered radioactivity excreted at each time interval and cumulatively through that 
interval are tertiary endpoints. 
Individual participant and median data profiles for total radioactivity will be graphically 
presented for the cumulative recovery of radioactivity in urine, feces and their combination in 
Period 1 only. Emesis, if any, will be collected during 24 hours post oral dose, but these 
participants will not necessarily be excluded from analysis (see Section 9.3 for additional 
details on evaluable participants). The total recovery of radioactivity in urine, feces (and 
emesis, if any) and their combination will be listed and summarized for Period 1 only. 
9.3.2.2. Metabolite Profiling and Metabolite Identification (Period 1) 
Plasma, urine and fecal samples collected in Period 1 will be analyzed for metabolites of 
PF-07081532. Major metabolites of PF-07081532 in plasma, urine and feces may be 
identified if possible. Contributions of parent and each major metabolite to total radioactivity 
recovered in urine and feces and to circulating radioactivity in plasma will be quantified. 
Results of the metabolic profiling analysis will be detailed in a separate report and will be 
summarized within the CSR. 
9.3.3. Secondary Endpoint(s) Analysis 
9.3.3.1. Pharmacokinetic Parameters 
9.3.3.1.1. Plasma 
• For Period 1, following a single oral administration of [14C]PF-07081532, oral PK 
parameters for total [14C] radioactivity will be derived from the concentration 
equivalent-time profiles, where appropriate. Additionally, PK parameters for 
PF-07081532 will be derived from the concentration-time profiles based on 
LC/MS/MS analysis of plasma samples. 
• For Period 2, following a single oral dose of unlabeled PF-07081532, PK parameters 
for PF-07081532 will be derived from the concentration-time profiles based on 
LC/MS/MS analysis of plasma samples (note that this reflects a tertiary endpoint and 
as such is also listed under Section 9.3.4). 


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• For Period 2, following a single IV microdose dose of [14C]PF-07081532 at 1 hour 
post oral dose, IV plasma PK parameters of [14C]PF-07081532 will be derived from 
plasma radioactivity concentration-time profiles following chromatographic 
separation of [14C]PF-07081532. 
 
Parameter 
Definition 
Method of Determination 
AUClast 
Area under the plasma 
concentration-time profile from time 
0 to time of the last quantifiable 
concentration (Clast) 
Linear/Log trapezoidal rule 
AUClast(dn) 
Dose-normalized AUClast, in Period 2 
only 
AUClast/Dose 
AUCinfa 
Area under the plasma 
concentration-time profile from time 
zero 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, 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 
AUCinf(dn)a 
Dose-normalized area under the 
plasma concentration-time profile 
from time zero extrapolated to 
infinite time, in Period 2 only 
AUCinf/Dose 
Cmax 
Maximum plasma concentration 
Observed directly from data 
Cmax(dn) 
Dose-normalized maximum plasma 
concentration, in Period 2 only 
Cmax/Dose 
Tmax 
Time for Cmax 
Observed directly from data as time of first 
occurrence 
t½a 
Terminal elimination half-life 
Loge(2)/kel 
CLa (IV) 
CL: systemic clearance following IV 
administration 
Dose/AUCinf 
MRTa (IV) 
Mean residence time 
AUMCinf/AUCinf - (infusion time/2) 
Vssa (IV) 
Vss: Steady-state volume of 
distribution following IV 
administration 
Vss = CL × MRT 
CL/Fa (oral) 
Apparent clearance of PF-07081532 
following oral administration 
Dose/AUCinf 
Vz/Fa (oral) 
Apparent volume of distribution of 
PF-07081532 following oral 
administration 
Dose /(AUCinf*kel) 
a If data permit. 
 
Actual PK sampling times will be used in the derivation of PK parameters, defined relative to 
the time of the oral dose for the parameters referring to oral dosing and relative to the start of 
the 15-minute IV infusion for the parameters referring to IV dosing. Actual administered 
[14C] doses will be used for the total [14C] and [14C]PF-07081532 PK parameter calculations. 


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Plasma PK parameters above will be listed and summarized descriptively as appropriate, by 
analyte (total [14C], unlabeled PF-07081532, and [14C]PF-07081532) and route of 
administration (oral or IV), as specified in the SAP. 
Individual participant profiles of the concentration-time data will be plotted by analyte and 
route of administration using the actual PK sampling times. Summary plots (median and 
mean) of the concentration-time data will be presented for each analyte and for route of 
administration using the nominal PK sampling times. 
Plasma concentrations/concentration equivalents for each of the analytes will be listed and 
summarized descriptively by nominal PK sampling time and route of administration. 
9.3.3.1.2. Absolute Bioavailability 
F will be estimated (in Period 2 only) as the ratio of adjusted geometric means of 
dose-normalized AUCinf (if data permit, otherwise AUClast) following oral, unlabeled, 
PF-07081532 and IV, [14C]PF-07081532 which is equivalent to the following equation: 
F = [PF-07081532_AUCpo/PF-07081532_AUCiv]*[PF-07081532_Doseiv/PF- 
07081532_Dosepo] 
Natural log transformed AUCinf(dn) (if data permit, otherwise AUClast(dn)) from Period 2 
will be analyzed using a mixed effect model with treatment as a fixed effect and participant 
as a random effect. Estimates of the adjusted (least squares) mean differences 
(Test-Reference) and the corresponding 90% confidence interval will be obtained from the 
model. The adjusted mean differences and 90% confidence intervals for the differences will 
be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% confidence interval for the ratio where IV [14C]PF-07081532 is the 
reference formulation and unlabeled oral PF-07081532 is the test formulation. 
Summary plasma concentrations (dose-normalized) of orally administered PF-07081532 and 
IV administered [14C]PF-07081532 in Period 2 will be presented in the same plot by route of 
administration using nominal sampling times. 
9.3.3.1.3. Fraction Absorbed 
9.3.3.1.3.1. Urine Parameters 
The following urine parameters will be calculated following single dose administration of a 
microtracer dose of [14C]PF-07081532 (oral and IV administration), as data permit. Residual 
[14C] levels from Period 1 will be accounted for using an appropriate method, based on AMS 
principles and methodology. 


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Parameter 
Definition 
Method of Determination 
Total [14C]_Urine_PO 
Total cumulative radioactivity 
excreted into urine from time zero up 
to the time of last measurable 
concentration following oral 
administration of [14C]PF-07081532 
(Period 1 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for 
each collection interval 
Total 
[14C]_Urine_PO_Trunc* 
Total cumulative radioactivity 
excreted into urine from time zero up 
to Day 7 (matching duration of 
Period 2 urine collection up to 
discharge) following oral 
administration of [14C]PF-07081532 
(Period 1 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for 
each collection interval 
Total [14C]_Urine_IV 
Total cumulative radioactivity 
excreted into urine from time zero up 
to the time of last measurable 
concentration following IV 
administered [14C]PF-07081532 
microdose (Period 2 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for 
each collection interval 
% [14C]_Urine_PO 
% of radioactivity in the urine 
following oral administration, 
expressed as a percent of the 
radioactive dose administered 
(Period 1 only) 
(Total [14C]_Urine_PO/[14C] Dosepo) 
*100 
where, 
[14C] Dosepo is orally administered 
actual dose of [14C]PF-07081532 
% [14C]_Urine_PO_Trunc* 
% of radioactivity in the urine up to 
Day 7 (matching duration of Period 2 
urine collection up to discharge) 
following oral administration, 
expressed as a percent of the 
radioactive dose administered 
(Period 1 only) 
(Total [14C]_Urine_PO_Trunc/[14C] 
Dosepo) *100 
where, 
[14C] Dosepo is orally administered 
actual dose of [14C]PF-07081532 
% [14C]_Urine_IV 
% of radioactivity in the urine 
following IV administration 
expressed as a percent of the 
radioactive dose administered 
(Period 2 only) 
(Total 14C _Urine_IV/[14C] Doseiv) 
*100 
where, 
[14C] Doseiv is [14C] IV administered 
actual dose of [14C]PF-07081532 
*_Trunc parameters may not be calculated and reported if not applicable (ie, no participant is discharged 
after Day 7 in Period 1). 
 
The above parameters will be listed and summarized using descriptive statistics, as specified 
in the SAP. 
9.3.3.1.3.2. Calculation of Fa 
Fa will be estimated as the ratio of adjusted geometric means of the % of administered 
radioactive dose excreted into urine following oral and IV administration of 
[14C]PF-07081532 in Periods 1 and 2, respectively. Urine radioactivity up to Day 7 will be 
used for Period 1 to match the duration of Period 2 urine collection up to discharge: 
Fa = [% [14C]_Urine_PO_Trunc/% [14C]_Urine_IV] 


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Natural log transformed % [14C]_Urine_PO_Trunc (if data permit) from Period 1 
and % [14C]_Urine_IV (if data permit) from Period 2 will be analyzed using a mixed effect 
model with treatment as a fixed effect and participant as a random effect. Estimates of the 
adjusted (least squares) mean differences (Test-Reference) and the corresponding 
90% confidence interval will be obtained from the model. The adjusted mean differences and 
90% confidence intervals for the differences will be exponentiated to provide estimates of the 
ratio of adjusted geometric means (Test/Reference) and 90% confidence interval for the ratio 
where IV [14C]PF-07081532 is the reference formulation and oral [14C]PF-07081532 is the 
test formulation. 
9.3.3.2. 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 and [14C] measurements collected at 
screening will be reported. 
9.3.3.2.1. Electrocardiogram Analyses 
Changes from baseline for the ECG parameters HR, QTcF, PR interval, and QRS complex 
will be summarized by treatment and time. 
The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
 
Safety QTcF Assessment 
 
Degree of Prolongation 
Mild (ms) 
Moderate (ms) 
Severe (ms) 
Absolute value 
>450-480 
>480-500 
>500 
Increase from baseline 
30-60 
>60 
In addition, the number of participants with uncorrected QT values >500 ms will be 
summarized. 


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9.3.4. Tertiary/Exploratory Endpoint(s) Analysis 
9.3.4.2. Cumulative Rate of Excretion (Period 1) 
See Section 9.3.2.1. 
9.3.4.3. Pharmacokinetics Parameters (Oral Unlabeled PF-07081532 - Period 2) 
See Section 9.3.3.1.1. 
9.3.5. Other Analyses 
Details on the analysis of data derived from the collected CCI 
 samples (if assayed) 
will be provided in the SAP. Results of such analyses (if performed) may not be included in 
the CSR. 
Pharmacogenomic or biomarker data from Retained Research Samples may be collected 
during or after the trial and retained for future analyses; the results of such analyses are not 
planned to be included in the CSR. 
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 modeling, and/or supporting clinical 
development. 
9.5. Sample Size Determination 
A sample size of approximately 6 participants has been chosen based on the industry 
standard sample size for mass balance and radiolabeled microtracer studies and in line with 
latest FDA draft guidance (May 2022).9 This sample size was not chosen based on any 
empirical data or hypothesis testing criteria. The sample size has been selected to ensure that 
6 participants provide evaluable data after completing Period 1; with intent to replace 
participants who prematurely withdraw (or offer non-evaluable or partially evaluable data). 
In Period 2, participants who are prematurely withdrawn may be replaced at the discretion of 
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, European Medical Device Regulation 2017/745 for 
clinical device research, and all other applicable local regulations. 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 


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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of. 
10.1.2. Financial Disclosure 
Investigators and 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 the investigator’s 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 participant is fully informed about the nature and 
objectives of the study, the sharing of data related to the study, and possible risks associated 
with participation, including the risks associated with the processing of the participant’s 
personal data. 
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities. 
The investigator further must ensure that each study participant is fully informed about their 
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD. 


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Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations. 
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 and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law. 
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws. 
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
The sponsor maintains standard operating procedures on how to respond in the event of 
unauthorized access, use, or disclosure of sponsor information or systems. 
10.1.5. Committees Structure 
A data monitoring committee or independent oversight committee will not be utilized. 
10.1.5.1. Data Monitoring Committee 
This study will not use an E-DMC. 


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10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov 
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law. 
EudraCT/CTIS 
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements. 
www.pfizer.com 
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized. 
Documents within marketing applications 
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized. 
Data sharing 
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized. 


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Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
10.1.7. Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document. 
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties. 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source 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. 


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The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings. 
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 the Source 
Document Locator, which is maintained by the sponsor. 
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The sponsor or designee will perform monitoring 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, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 


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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. 
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 
For multicenter trials, the primary publication will be a joint publication developed by the 
investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. 
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study. 
Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section. 
The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. If any patent action is required to protect intellectual property rights, the 
investigator agrees to delay the disclosure for a period not to exceed an additional 60 days 
upon request from Pfizer. This allows Pfizer to protect proprietary information and to provide 


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comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study-intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
study results. For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication. 
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication. 
10.1.11. Sponsor’s Medically Qualified Individual 
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the supporting study documentation/study portal or other electronic 
system. 
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from nonstudy healthcare professionals, participants are provided with 
an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol and 
study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center 
number. 
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. The Pfizer Call Center number is to be used when the investigator and site staff 
are unavailable. The Pfizer Call Center number is not for use by the participant directly; if a 
participant calls that number directly, they will be directed back to the investigator site. 


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10.2. Appendix 2: Clinical Laboratory Tests 
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. 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 3. 
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 
Creatinine (Scr) 
Cystatin C (Scys) on Day -1 only 
eGFRa 
Serum Glucose (fasting) 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (Bicarbonate) 
AST 
ALT 
Alkaline phosphatase 
GGT 
T bili 
Direct bilirubinb,c 
Indirect bilirubinb,c 
Creatine kinaseb,d 
Uric acid 
Albumin 
Total protein 
pH 
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte esterase 
Urobilinogen 
Urine bilirubin 
Microscopye 
Other tests as part of clinical 
laboratory tests: 
COVID-19 testf 
At screening only: 
• Serology: HBsAg, HCVAb 
(if positive, HCV RNA) and 
HIV 
At screening and Day -1 only: 
• Urine drug testg 
For suspected DILI: 
• AST, ALT 
• T bili, direct and indirect 
bilirubin 
• Total bile acids, GGT 
• Albumin 
• Alkaline phosphatase 
• CK 
• PT, INR 
• Acetaminophen/paracetamol 
or 
protein adduct levels 
For suspected DICI/DIKI: 
Creatinine (Scr) 
Cystatin C (Scys)h 
eGFRh 
UACR 
a. 
eGFR should be calculated using the 2021 CKD-EPI Scr only equations, see Appendix 7. 
b. 
At screening and Day -1 only, unless conditions for testing are met after Day 1 per notes “c” and “d” below. 
c. 
After Day 1, direct and indirect bilirubin assessed only when T bili is > ULN. 
d. 
After Day 1, creatine kinase assessed only when ALT is > ULN. 
e. 
If abnormal urine dipstick results including positive results for blood, protein, nitrites or leukocyte esterase. 
f. 
Assessment of risk for, symptoms of or testing for COVID-19 may be performed at screening, admission to the 
CRU and/or at other times during the study at investigator discretion and according to local site policies. 
g. 
Minimum testing requirements include cocaine, THC, opiates, barbiturates, benzodiazepines and amphetamines 
(including XTC). 
h. 
For suspected DICI/DIKI, reflex measurement of Scys will be conducted and eGFR will be calculated using both 
the 2021 CKD-EPI Scr only and the 2021 CKD-EPI Scr-Scys Combined equations, see Appendix 7. 
 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 


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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. Upon completion of the study, these retained safety 
samples may be used for the assessment of exploratory safety biomarkers, unexpected safety 
findings, or other exploratory purposes. 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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Events Meeting the AE Definition 
• 
Any abnormal laborato1y test results (hematology, clinical chetnistty, or minalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measmements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnonnal laborat01y 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/smgical intervention; 
• 
Leads to a change in study dosing (outside of any protocol-specified dose 
adjusttnents) or discontinuation from the study, significant additional 
concotnitant dmg tt-eattnent, or other therapy. 
• 
 Exacerbation of a chronic or intennittent preexisting condition, including an 
increase in either frequency and/or intensity of the condition. 
• 
 New condition detected or diagnosed after study inte1vention adtninistt·ation, even 
though it may have been present before the sta1t of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected dmg-dmg interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
inte1vention or a concotnitant medication. Overdose per se will not be repo1ted as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-hanning intent. Such overdoses should be repo1ted regardless of 
sequelae. 
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 occmTence 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 
abnonnal laborat01y finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
 
 


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Events 
Meeting the AE Definition 
• 
Any clinically significant abno1mal laborato1y findings or other abnonnal safety 
assessments that are associated with the underlying disease, lmless judged by the 
investigator to be more severe than expected for the pa1ticipant'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 
pa1ticipant's condition. 
• 
Medical or smgical procedme (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
Situations in which an untoward medical occmTence 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 sta1t 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 tenn "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 tnight have caused death if it were more severe. 
c.  Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the paiticipant has been adtnitted (usually 
involving at least an overnight stay) at the hospital or emergency wai·d for obse1vation 
and/or treatment that would not have been appropriate in the physician's office or 
outpatient setting. Complications that occur during hospitalization ai·e AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether "hospitalization" occmTed or was necessa1y, 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 tenn disability means a substantial disrnption of a person's ability to conduct 
nonnal life functions. 
•  This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diaIThea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent eve1yday life functions but do not constitute a substantial disrnption. 
e.  Is a congenital anomaly/birth defect 
f. 
 Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic 
The event may be suspected from clinical symptoms or laborat01y findings indicating 
an infection in a pa11icipant exposed to a Pfizer product. The te1ms "suspected 
transmission" and "transtnission" are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by phatmacovigilance 
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 patticipant 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. 
• Exainples 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 dtug 
dependency or dtug 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 sUllllnat·izes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Repo11 Fotm 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. 
 
* 
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using the 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. 
• 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. 
 
 
 
 
 
PFIZER CONFIDENTIAL 
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 EDP or EDB 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF 
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)* 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)** 
Environmental or 
occupational exposure to 
the product under study 
to a nonparticipant (not 
involving EDP or EDB) 
None. Exposure to a study 
non-participant is not 
collected on the CRF 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported*** 


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• 
 It is not acceptable for the investigator to send photocopies of the participant's 
medical records to Pfizer Safety in lieu of completion of the CT SAE Repo1i 
Fonn/AE or SAE CRF page. 
• 
 There may be instances when copies of medical records for ce1iain cases are 
requested by Pfizer Safety. In this case, all paiiicipant identifiers, with the 
exception of the paiiicipant 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 infonnation. 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 repo1ied 
during the study and assign it to I of the following categories: 
• 
Mild: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usualADL. 
• 
Moderate: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual ADL, causing discomf01i, 
but poses no significant or permanent risk of haim to the research pa1iicipant. 
• 
Severe: A type of AE that intenupts usual ADL, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
An event is defined as "serious" when it meets at least I of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
• 
 The investigator is obligated to assess the relationship between study inte1vention 
and each occunence of each AE or SAE. The investigator will use clinical 
judgment to dete1mine 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 rnled out. 


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• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• 
The investigator will also consult the IB and/or product infonnation, for marketed 
products, in their assessment. 
• 
For each AE or SAE, the investigator must document in the medical notes that they 
have reviewed the AE or SAE and have provided an assessment of causality. 
• 
There may be situations in which an SAE has occmTed and the investigator has 
minimal infonnation to include in the initial repo1t to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor. 
• 
The investigator may change their opinion of causality in light of follow-up 
info1mation and send an SAE follow-up repo1t with the updated causality 
assessment. 
• 
 The causality assessment is one of the criteria used when dete1mining regulato1y 
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 repo1ting 
pmposes, as defined by the sponsor. In addition, if the investigator dete1mines that 
an SAE is associated with study procedmes, the investigator must record this 
causal relationship in the somce documents and CRF, and repo1t such an 
assessment in the dedicated section of the CT SAE Repo1t Fo1m and in accordance 
with the SAE repo1ting requirements. 
Follow-Up of AEs and SAEs 
• 
 The investigator is obligated to perfo1m or aITange for the conduct of supplemental 
measmements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the natme and/or causality of the AE or SAE as fully as 
possible. This may include additional laborato1y tests or investigations, 
histopathological examinations, or consultation with other healthcare providers. 
• 
 If a paiticipant dies dming paiticipation in the study or dming a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmo1tem findings, including histopathology. 


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• 
New or updated infom1ation 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 info1mation. 
10.3.4. Reporting of SAEs 
SAE Reporting to Pfizer Safety via an Electronic DCT 
• 
The primaiy mechanism for repo1iing an SAE to Pfizer Safety will be the 
electronic DCT. 
• 
 If the electronic system is unavailable, then the site will use the paper SAE DCT 
(see next section) to rep01i the event within 24 hours. 
• 
 The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or 
paper f01m (as applicable) as soon as the data become available. 
• 
After the study is completed at a given site, the electronic DCT will be taken 
off-line to prevent the entiy of new data or changes to existing data. 
• 
If a site receives a repo1i of a new SAE from a study pa1iicipant or receives updated 
data on a previously reported SAE after the electi·onic DCT has been taken off-line, 
then the site can repo1i this info1mation on a paper SAE f01m (see next section) or 
to Pfizer Safety by telephone. 
SAE Reporting to Pfizer Safety via the CT SAE Report Form 
• 
Facsimile ti·ansnussion of the CT SAE Report Fonn is the prefened method to 
ti·ansmit this information to Pfizer Safety. 
• 
In circumstances when the facsimile is not working, an alternative method should 
be used, eg, secured (Transport Layer Security) or password-protected email. If 
none of these methods can be used, notification by telephone is acceptable with a 
copy of the CT SAE Repo1i Fo1m 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 Fo1m pages within the designated repo1iing 
time fraines. 


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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria 
As the calculated safety margin between the estimated maternal exposure due to seminal 
transfer and the NOAEL for serious manifestations of developmental toxicity in nonclinical 
studies is ≥100-fold (see Section 4.2.1), no contraception methods are required by the 
sponsor for male participants receiving PF-07081532. 
If more conservative guidelines on contraception are required (for example, per local 
regulations or IRBs/ECs) the male participants in this study may be asked to use 
contraception. In such cases, full detail will be provided in the informed consent document. 
10.4.2. Female Participant Reproductive Inclusion Criteria 
Not applicable. 
10.4.3. Woman of Childbearing Potential 
Not applicable. 
10.4.4. Contraception Methods 
Contraceptive use by study participants should be consistent with local 
availability/regulations regarding the use of contraceptive methods for those participating in 
clinical trials. 


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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 T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be 
elevated within the same laboratory sample). In rare instances, by the time T bili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST OR ALT in addition to T bili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded. 
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values: 
• Participants with AST/ALT and T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili value 
≥2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available. 
• For participants with baseline AST OR ALT OR T bili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline: 
• Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values ≥2 times the baseline values AND ≥3 × ULN; or ≥8 × ULN (whichever is 
smaller). 
• Preexisting values of T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller). 


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Rises in AST/ALT and T bili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, 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 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 


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10.7. Appendix 7: Kidney Safety: Monitoring Guidelines 
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury 
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum 
creatinine (Scr measurement to estimate glomerular filtration rate [Scr-based eGFR] or 
eCrCl). Baseline and postbaseline serum Scys makes it feasible to distinguish AKI from 
other causes of Scr increase. If Scr increase is confirmed after baseline, then reflex 
measurement of Scys is indicated to estimate the combined Scr-Scys eGFR calculation (for 
adults only). 
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care. 
10.7.2. Age-Specific Kidney Function Calculation Recommendations 
10.7.2.1. Adults (18 Years and Above)-2021 CKD-EPI Equations 
 
2021 CKD- 
EPI 
Scr Only 
Scr 
(mg/dL) 
Scys 
(mg/L) 
Recommended eGFR Equation 
Female 
if ≤0.7 
N/A 
eGFR = 143 × (Scr/0.7)-0.241 × (0.9938)Age 
Female 
if >0.7 
N/A 
eGFR = 143 × (Scr/0.7)-1.200 × (0.9938)Age 
Male 
if ≤0.9 
N/A 
eGFR = 142 × (Scr/0.9)-0.302 × (0.9938)Age 
Male 
if >0.9 
N/A 
eGFR = 142 × (Scr/0.9)-1.200 × (0.9938)Age 
2021 CKD- 
EPI 
Scr-Scys 
Combined 
Scr 
(mg/dL) 
Scys 
(mg/L) 
Recommended eGFR Equation 
Female 
if ≤0.7 
if ≤0.8 
eGFR = 130 × (Scr/0.7)-0.219 × (Scys/0.8)-0.323 × (0.9961)Age 
Female 
if ≤0.7 
if >0.8 
eGFR = 130 × (Scr/0.7)-0.219 × (Scys/0.8)-0.778 × (0.9961)Age 
Female 
if >0.7 
if ≤0.8 
eGFR = 130 × (Scr/0.7)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age 
Female 
if >0.7 
if >0.8 
eGFR = 130 × (Scr/0.7)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age 
Male 
if ≤0.9 
if ≤0.8 
eGFR = 135 × (Scr/0.9)-0.144 × (Scys/0.8)-0.323 × (0.9961)Age 
Male 
if ≤0.9 
if >0.8 
eGFR = 135 × (Scr/0.9)-0.144 × (Scys/0.8)-0.778 × (0.9961)Age 
Male 
if >0.9 
if ≤0.8 
eGFR = 135 × (Scr/0.9)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age 
Male 
if >0.9 
if >0.8 
eGFR = 135 × (Scr/0.9)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age 
Inker LA et al. N Engl J Med. 2021;385:1737-49.10 
10.7.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities 
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO 
criteria. 


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ECG Findings That May Qualify as AEs 
• 
Marked sinus bradycardia (rate <40 bpm) lasting minutes. 
• 
New PR interval prolongation >280 ms. 
• 
New prolongation of QTcF to >480 ms (absolute) or by 60 ms from baseline. 
• 
New-onset atrial flutter or fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm. 
• 
New-onset type I second-degree (Wenckebach) AV block of>30 seconds' 
duration. 
• 
Frequent PVCs, triplets, or sho1t intervals (<30 seconds) of consecutive ventricular 
complexes. 
ECG Findings That May Qualify as SAEs 
• 
QTcF prolongation >500 ms. 
• 
New ST-T changes suggestive of myocardial ischemia. 
• 
New-onset LBBB (QRS complex>l20 ms). 
• 
New-onset right bundle branch block (QRS complex>120 ms). 
• 
Symptomatic bradycardia. 
• 
Asystole: 
• 
 In awake, symptom-free pa1ticipants 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 
>120bpm. 
• 
 Sustained supraventricular tachycardia (rate >120 bpm) ("sustained"= sho1i 
duration with relevant symptoms or lasting >1 minute). 
10.8. Appendix 8: ECG Findings of Potential Clinical Concern 
 


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• Ventricular rhythms >30 seconds' dmation, including idioventricular rhythm (HR 
<40 bpm), accelerated idioventricular rhythm (HR >40 bpm to <l 00 bpm), and 
monomorphic/polymorphic ventricular tachycardia (HR> I00 bpm [such as 
torsades de pointes]). 
• Type II second-degree (Mobitz II) AV block. 
• Complete (third-degree) heait block. 
ECG Findings That Qualify as SAEs 
• Change in pattern suggestive of new myocardial infarction. 
• Sustained ventricular tachyaIThythmias (>30 seconds' dmation). 
• 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 aIThythmia classified as an adverse 
expenence. 
The enumerated list of major events of potential clinical concem are re.commended as "aletts" or 
notifications from the core ECG laborato1y to the investigator and Pfizer study team, and not to be 
considered as all-inclusive of what to be repotted as AEs/SAEs. 


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Drug Category 
Drugs (Therapeutic Class) 
Washout Period 
Requirement Prior to 
the First Dose of Study 
Intervention 
CYP3A 
Inhibitor 
(strong) 
Boceprevir (Antiviral), 
Ceritinib (Kinase Inhibitor), 
Clarithromycin (Antibiotic), 
Cobicistat (Phannacokinetic Enhancer), 
Conivaptan (Diuretic), 
Danoprevir and Ritonavir (Antiviral), 
Elvitegravir and Ritonavir (Treatment of AIDS), 
Grapefrnit juice (Food Product), 
Idelalisib (Kinase Inhibitor), 
Indinavir (Protease Inhibitor), 
Indinavir and Ritonavir (Protease Inhibitor), 
Itraconazole (Antifungal), 
Josamycin (Antibiotic) 
Ketoconazole (Antifungal), 
LCL161 (Cancer Treatment), 
Lonafamib (Misc agent; Rare diseases) 
Lopinavir and Ritonavir (Protease Inhibitor), 
Mibefradil (Calcium Channel Blocker), 
Mifepristone (Antiprogestin), 
Nefazodone (Antidepressant), 
Nelfinavir (Protease Inhibitor), 
Niimatrelvir + Ritonavir (Protease hlhibitor), 
Posaconazole (Antifungal), 
14 days or 5 half-lives, 
whichever is longer 
10.10. Appendix 10: Prohibited Concomitant Medications That May Result in DDI 
The prohibited concomitant medications listed below should not be taken with PF-07081532 
for the period of time at least equal to the required washout period listed in the table, and 
throughout the conduct of the study. 
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
After consulting with the sponsor, the investigator will make a judgment on the ongoing 
paiiicipation of any participant with prohibited medication use during the study. 
This list of drngs prohibited for potential DDI concerns with the IMP may be revised during 
the course of the study with written notification from sponsor, to include or exclude specific 
diugs or diug categories for various reasons (eg, emerging DDI results for the IMP, 
availability of new infonnation in literature on the DDI potential of other diugs). 
This is not an all-inclusive list. Site staff should consult with the sponsor or designee with 
any questions regarding potential DDI. 
Investigators should consult the product label for any other medication used during the study 
for info1mation regarding medication that is prohibited for concomitant use. 
 


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Drug Category 
Drugs (Therapeutic Class) 
Washout Period 
Requirement Prior to 
the First Dose of Study 
Intervention 
Ribociclib (Kinase Inhibitor), 
Ritonavir (Protease Inhibitor), 
Saquinavir (Protease Inhibitor), 
Saquinavir and Ritonavir (Protease Inhibitor), 
Telaprevir (Antiviral), 
Telithromyci..11(Antibiotic), 
Tipranavir and Ritonavir (Protease Inhibitor), 
Troleandomycin(Antibiotic), 
Tucatinib (Kinase Inhibitor), 
Ombitasvir and Paritaprevir and Ritonavir and 
Dasabuvi.I·(Antiviral), 
Voriconazole (Antifungal) 
CYP3A Inducer 
(strong) 
Apalutamide (Antianclrogen), 
Avasimibe (Antilipemic), 
Carbamazepine (Anticonvulsant), 
Enzalutamide (Antiandrogen), 
Ivosidenib (Cancer Treatment), 
Lumacaftor (Cystic Fibrosis Treatment), 
Mitotane (Antineoplastic), 
Phenytoin (Anticonvulsant), 
Rifampin (Antibiotic), 
RifapentiI1e (Antibiotic), 
St. John's wo1t extract (Herbal Medication) 
5 half-lives plus 14 days 
CYP3A Inducer 
(moderate) 
Asllllaprevir and Beclabuvir and Daclatasvi.I· 
(Antiviral), 
Bosentan (Endothelill Receptor Antagonist), 
Cenobamate (Anticonvulsant), 
Dabrafenib (Ki..11ase Inhibitor), 
Efavirenz (Non-nucleoside Reverse Transcriptase 
Inhibitor), 
Elagolix (Gonadotropin-releasillg Ho1mone 
Receptor Antagonist), 
Etravirille (Non-nucleoside Reverse Transcriptase 
Inhibitor), 
LersiviriI1e (Non-nucleoside Reverse 
Transcriptase Inhibitor), 
Lenisurad (Antigout and Uricosuric Agent), 
Lopinavir (Protease Inhibitor), 
Lorlatillib (Ki..11ase Inhibitor), 
Metamizole / Dipyrone (Analgesic), 
Mitapivat (Pymvate Killase Activator), 
Modafinil (Psychostimulant), 
Nafcillill (Antibiotic), 
5 half-lives plus 14 days 


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Drug Category 
Drugs (Therapeutic Class) 
Washout Period 
Requirement Prior to 
the First Dose of Study 
Intervention 
Pexida1tinib (Kinase Inhibitor), 
P1imidone (Anticonvulsant), 
PF-06282999 (Myeloperoxidase Inactivator), 
Phenobarbital (Anticonvulsant), 
Rifabutin (Antibiotic), 
Semagacestat (Alzheimer's Disease & Dementia 
Treatment), 
Sotorasib (Kinase Inhibitor), 
Talviraline (Non-nudeoside Reverse 
Transcriptase Inhibitor), 
Telotristat Ethyl (Antidianheal), 
Thioridazine (Antipsychotic), 
Tipranavir and Ritonavir (Protease Inhibitor) 
OATP 
(1Bl/1B3) 
Inhibitor 
Atazanavir and Ritonavir (Protease Inhibitor), 
Boceprevir (Antiviral), 
Clarithromycin (Antibiotic), 
Cyclospoiine (Immunosuppressant), 
Eltrombopag (Thrombopoietin receptor agonist) 
Elythromycin (Antibiotic), 
Faldaprevir (Antiviral), 
Gemfibrozil (Fibric Acid Derivative), 
Grazoprevir (Antiviral), 
Itraconazole (Antifungal), 
Lete1movir (Antiviral), 
Lopinavir and Ritonavir (Protease Inhibitor), 
Rifampin, single dose (Antibiotic), 
Simeprevir (Antiviral) 
Telaprevir (Antiviral), 
Velpatasvir (Antiviral) 
14 days or 5 half-lives, 
whichever is longer 
CYP2C19 
Substratea 
BMS-823778 (Diabetes Treatment), 
Clobazam (Benzodiazepine), 
Clopidogrel (Antiplatelet),b 
Diazepam (Benzodiazepine), 
Gliclazide (Sulfonylurea), 
Hexobarbital (Hypnotic - Sedative), 
Mephobarbital (Anticonvulsant), 
Proguanil (Antimalarial), 
S-mephenytoin (Anticonvulsant), 
Tilidine (Treatment of Pain & Inflammation), 
Valproic acid (Anticonvulsant) 
14 days or 5 half-lives, 
whichever is longer 
UGTIAI 
Substrate 
Belinostat (Histone Deacetylase Inhibitor), 
IIinotecan (Topoisomerase Inhibitor) 
14 days or 5 half-lives, 
whichever is longer 


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a. 
The PPIs dexlansoprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole, although considered 
sensitive CYP2C19 substrates, are not listed above due to wide therapeutic index and no anticipated impact 
on their efficacy or safety. 
b. The PK interaction between PF-07081532 and clopidogrel has been clinically assessed (see PF-07081532 
IB). Out of abundance of caution, until further clinical or model-based assessment of whether the modest 
changes in exposure observed can elicit any clinically meaningful impact on efficacy/safety, 
co-administration of PF-07081532 with clopidogrel is prohibited. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Abbreviation 
Term 
A1 to A3 
albuminuria (KDIGO albuminuria severity standardization) 
Abs 
absolute 
ADL 
activity/activities of daily living 
ADME 
absorption, distribution, metabolism, and excretion 
AE 
adverse event 
AKI 
acute kidney injury 
ALT 
alanine aminotransferase 
AMS 
accelerator mass spectrometer 
API 
active pharmaceutical ingredient 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC24 
area under the concentration-time curve over 24 hours 
AUCinf 
area under the concentration-time curve to infinity 
AUClast 
area under the plasma concentration-time profile from time zero to 
the time of the last quantifiable concentration 
AUCtau 
area under the concentration-time curve at steady state over the 
dosing interval tau 
AV 
atrioventricular 
AxMP 
auxiliary medicinal product 
BBS 
Biospecimen Banking System 
BCS 
Biopharmaceutics Classification System 
BID 
twice a day 
BMI 
body mass index 
BP 
blood pressure 
bpm 
beats per minute 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CKD-EPI 
chronic kidney disease epidemiology 
CL 
clearance 
CL/F 
apparent clearance of drug from plasma 
Cmax 
maximum observed concentration 
CO2 
carbon dioxide (bicarbonate) 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
CRU 
clinical research unit 
CSR 
Clinical Study Report 
10.11. Appendix 11: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 


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Abbreviation 
Term 
CT 
clinical trial 
CTIS 
Clinical Trial Information System 
CYP 
cytochrome P450 
DCT 
data collection tool 
DDI 
drug-drug interaction 
DICI 
drug-induced creatinine increase 
DIKI 
drug-induced kidney injury 
DILI 
drug-induced liver injury 
dn 
dose-normalized 
EC 
ethics committee 
ECC 
emergency contact card 
ECG 
electrocardiogram or electrocardiography 
eCrCl 
estimated creatinine clearance 
eCRF 
electronic case report form 
EDB 
exposure during breastfeeding 
E-DMC 
External Data Monitoring Committee 
EDP 
exposure during pregnancy 
EDR 
extemporaneous dispensing record 
EFD 
embryo-fetal development 
eGFR 
estimated glomerular filtration rate 
eSAE 
electronic serious adverse event 
ET 
early termination 
EU 
European Union 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database) 
F 
absolute oral bioavailability 
Fa 
fraction of dose absorbed 
FDA 
Food and Drug Administration 
Fg 
fraction escaping gut metabolism 
Fh 
fraction escaping hepatic first-pass elimination 
FU 
follow-up 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP-1 
glucagon-like peptide-1 
GLP-1R 
glucagon-like peptide-1 receptor 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C antibody 
HIV 
human immunodeficiency virus 
HR 
heart rate 
IB 
Investigator’s Brochure 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 103 
 
 
 
 
 
Abbreviation 
Term 
ICD 
informed consent document 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ID 
identification 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
K2EDTA 
dipotassium ethylenediaminetetraacetic acid 
KDIGO 
Kidney Disease Improving Global Outcomes 
LBBB 
left bundle branch block 
LC/MS/MS 
liquid chromatography tandem mass spectrometric method 
LFT 
liver function test 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MEN2 
multiple endocrine neoplasia type 2 
MIST 
Metabolites in Safety Testing 
MQI 
medically qualified individual 
MRT 
mean residence time 
MTC 
medullary thyroid carcinoma 
NA 
not applicable 
NIMP 
noninvestigational medicinal product 
NOAEL 
no-observed-adverse-effect level 
OATP 
organic anion transporting polypeptide 
PD 
protocol deviation 
PE 
physical exam 
PK 
pharmacokinetic(s) 
PO 
oral(ly) 
PPI 
proton pump inhibitor 
PSSA 
Pfizer's Serious Adverse Event Submission Assistant 
PT 
prothrombin time 
PVC 
premature ventricular contraction/complex 
QD 
once daily 
QP 
qualified person 
QTc 
corrected QT interval 
QTcF 
QTc corrected using Fridericia’s formula 
qual 
qualitative 
RBC 
red blood cell 
SAE 
serious adverse event 
SAI 
site administration instructions 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 104 
 
 
 
 
 
Abbreviation 
Term 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
Scr 
serum creatinine 
Scys 
serum cystatin C 
SoA 
schedule of activities 
SOC 
system organ class 
SOP 
standard operating procedure 
SRSD 
Single Reference Safety Document 
SSID 
study-specific participant identification 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t½ 
plasma elimination half life 
T2DM 
type 2 diabetes mellitus 
TA 
Technical Agreement 
T bili 
total bilirubin 
TEAE 
treatment-emergent adverse event 
THC 
tetrahydrocannabinol 
Tmax 
time to reach Cmax 
UACR 
urine albumin/creatinine ratio 
UGT 
uridine 5’-diphospho-glucuronosyltransferase 
ULN 
upper limit of normal 
UPLC-HRMS 
ultra-high performance liquid chromatography coupled high 
resolution mass spectrometry 
US 
United States 
Vss 
steady-state volume of distribution 
Vz/F 
apparent volume of distribution 
WBA 
whole body autoradiography 
WBC 
white blood cell 
XTC 
ecstasy 


PF-07081532 
Protocol C3991006 
Final Protocol, 30 September 2022 
PFIZER CONFIDENTIAL 
Page 105 
 
 
11. REFERENCES 
1. 
Orskov C, Holst JJ, Knuhtsen S, et al. Glucagon-like peptides GLP-1 and GLP-2, 
predicted products of the glucagon gene, are secreted separately from pig small intestine 
but not pancreas. Endocrinology. 1986;119(4):1467-75. 
2. 
Kreymann B, Williams G, Ghatei MA, et al. Glucagon-like peptide-1 7-36: a 
physiological incretin in man. Lancet. 1987;2(8571):1300-4. 
3. 
Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of 
gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 
1997;273(5):E981-8. 
4. 
Flint A, Raben A, Astrup A, et al. Glucagon-like peptide 1 promotes satiety and 
suppresses energy intake in humans. J Clin Invest. 1998;101(3):515-20. 
5. 
EMA. First published: 11/02/2013. ICH M3 (R2) Non-clinical safety studies for the 
conduct of human clinical trials for pharmaceuticals. Available from: 
https://www.ema.europa.eu/en/ich-m3-r2-non-clinical-safety-studies-conduct-human- 
clinical-trials-pharmaceuticals. Accessed on: 28 Jul 2022. 
6. 
Banholzer ML, Wandel C, Barrow P, et al. Clinical trial considerations on male 
contraception and collection of pregnancy information from female partner: update. 
Clin Transl Med. 2016;5(1):23-37. 
7. 
Lozac'h F, Fahrni S, Maria DD, et al. Evaluation of cAMS for 14C microtracer ADME 
studies: opportunities to change the current drug development paradigm. Bioanalysis. 
2018;10 5:321-339. 
8. 
Raje S, Callegari E, Sahasrabudhe V, et al. Novel Application of the Two‐Period 
Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction 
Absorbed of Ertugliflozin. Clinical and Translational Science. 2018;11(4):405-411. 
9. 
US Food and Drug Administration. Clinical Pharmacology Considerations for Human 
Radiolabeled Mass Balance Studies, Guidance for Industry, DRAFT GUIDANCE. May 
2022. Available from: https://www.fda.gov/media/158178/download. Accessed on: 28 
Jul 2022. 
10. Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based 
Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-1749. 

SAP_001.pdf: 
Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 1 of 24 
 
 
 
 
 
 
 
 
 
Protocol C3991006 
 
 
 
 
 
A PHASE 1, OPEN-LABEL, 2-PERIOD, FIXED SEQUENCE STUDY TO 
INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND 
EXCRETION OF [14C]PF-07081532 AND TO ASSESS THE ABSOLUTE 
BIOAVAILABILITY AND FRACTION ABSORBED OF PF-07081532 IN HEALTHY 
MALE PARTICIPANTS USING A [14C]-MICROTRACER APPROACH 
 
 
 
 
 
 
 
 
 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
 
 
 
 
 
Version: 
1 
Date: 
11 Jan 2023 
. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 2 of 24 
 
 
TABLE OF CONTENTS 
LIST OF TABLES .................................................................................................................... 4 
APPENDICES ........................................................................................................................... 4 
1. VERSION HISTORY ........................................................................................................... 5 
2. INTRODUCTION ................................................................................................................. 5 
2.1. Modifications to the Analysis Plan Described in the Protocol ..................................5 
2.2. Study Objectives, Endpoints, and Estimands ............................................................5 
2.3. Study Design ............................................................................................................ 6 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS .................................................................................................................. 7 
3.1. Primary Endpoint(s) ...................................................................................................7 
3.1.1. Extent of Excretion (Period 1 Only) .............................................................7 
3.1.2. Metabolite Endpoints ....................................................................................8 
3.2. Secondary Endpoint(s) ...............................................................................................8 
3.2.1. Plasma Pharmacokinetic Parameters ............................................................ 8 
3.2.2. Urine Pharmacokinetic Parameter ................................................................ 9 
3.3. Other Endpoint(s) ....................................................................................................11 
3.3.1. Cumulative Rate of Excretion (Period 1) ....................................................11 
3.3.2. Pharmacokinetics Parameters (Oral Unlabeled PF-07081532 - Period 
2) .................................................................................................................... 11 
.11 
.11 
3.4. Baseline Variables .................................................................................................. 11 
3.5. Safety Endpoints ......................................................................................................11 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) .................................................. 12 
5. GENERAL METHODOLOGY AND CONVENTIONS ................................................... 13 
5.1. Hypotheses and Decision Rules ..............................................................................13 
5.2. General Methods ..................................................................................................... 14 
5.2.1. Analyses for Continuous Endpoints ............................................................14 
5.2.2. Analyses for Categorical Endpoints ............................................................14 
5.2.3. Mixed Model for Continuous Endpoints ....................................................14 
5.3. Methods to Manage Missing Data .......................................................................... 15 
5.3.1. Plasma Pharmacokinetic Parameters .......................................................... 15 
CCI 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 3 of 24 
 
 
6. ANALYSES AND SUMMARIES ...................................................................................... 16 
6.1. Primary Endpoint(s) .................................................................................................16 
6.1.1. Extent of Excretion (Period 1 Only) ...........................................................16 
6.1.2. Metabolic Profiling and Metabolite Identification ..................................... 16 
6.2. Secondary Endpoint(s) .............................................................................................16 
6.2.1. Plasma PK parameters of PF-07081532 and total radioactivity in 
Period 1 and [14C]PF-07081532 in Period 2 ................................................... 16 
6.2.2. Absolute Bioavailability ............................................................................. 18 
6.2.3. Fraction Absorbed ...................................................................................... 18 
6.3. Other Endpoint(s) ....................................................................................................19 
6.3.1. Cumulative recovery of radioactivity excreted in Urine, Feces and 
Combined .........................................................................................................19 
6.3.2. Plasma PK parameters of PF-07081532 in Period 2 .................................. 19 
19 
20 
6.3.5. Banked Biospecimens ................................................................................ 20 
6.4. Subset Analyses ...................................................................................................... 20 
6.5. Baseline and Other Summaries and Analyses ........................................................ 20 
6.5.1. Baseline Summaries ................................................................................... 20 
6.5.2. Study Conduct and Participant Disposition ................................................20 
6.5.3. Concomitant Medications and Nondrug Treatments ..................................20 
6.6. Safety Summaries and Analyses ............................................................................. 20 
6.6.1. Adverse Events .......................................................................................... 21 
6.6.2. Laboratory Data ......................................................................................... 21 
6.6.3. Vital Signs .................................................................................................. 21 
6.6.4. Electrocardiograms (ECG) ......................................................................... 21 
7. INTERIM ANALYSES ...................................................................................................... 22 
7.1. Introduction ............................................................................................................. 22 
7.2. Interim Analyses and Summaries ........................................................................... 22 
8. REFERENCES .................................................................................................................... 22 
9. APPENDICES ..................................................................................................................... 23 
CCI 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 4 of 24 
 
 
LIST OF TABLES 
Table 1. 
Summary of Changes .................................................................................. 5 
Table 2. 
Summary of plasma PK Parameters to be calculated .................................. 9 
Table 3. 
Summary statistics to be produced for Plasma PK Parameters ................. 17 
APPENDICES 
Appendix 1. Example SAS Code for Mixed Model ................................................................. 23 
Appendix 2. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern ...... 23 
Appendix 3. List of Abbreviations ........................................................................................... 24 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 5 of 24 
 
 
1. VERSION HISTORY 
Table 1. 
Summary of Changes 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1 
11 Jan 2023 
Original 
30 Sep 2022 
N/A 
N/A 
 
2. INTRODUCTION 
The purpose of the study is to assess the metabolism and extent of excretion of 
[14C]PF-07081532 in urine and feces, following oral administration, in the fed state, in 
healthy male participants. This information will enable assessment of clearance mechanisms 
of PF-07081532 as well as identify disproportionate metabolites that should be qualified to 
adhere to the ICH M3 (R2) MIST guidance. In addition, this study will characterize the 
fraction of dose absorbed and the bioavailability of orally administered PF-07081532 in the 
fed state, in reference to an IV dose of [14C]PF-07081532, while it will also assess PK 
parameters following both oral and IV administration of [14C]PF-07081532. 
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C3991006. 
2.1. Modifications to the Analysis Plan Described in the Protocol 
Not Applicable 
2.2. Study Objectives, Endpoints, and Estimands 
 
Type 
Objective 
Endpoints 
Primary 
PK 
Section 6.1.1 
• To characterize the extent of excretion of 
total radioactivity in urine, feces, and 
emesis (if any) following administration of 
a single oral dose of [14C]PF-07081532. 
• Total recovery of radioactivity in urine, feces, and 
emesis (if any), and both routes combined, expressed 
as a percent of total oral radioactive dose 
administered. 
PK 
Section 6.1.2 
• To characterize the metabolic profile and 
identify circulating and excreted 
metabolites following administration of a 
single oral dose of [14C]PF-07081532. 
• Metabolic profiling/identification and determination 
of relative abundance of [14C]PF-07081532 and the 
metabolites of [14C]PF-07081532 in plasma, urine, 
and feces. 
Secondary 
PK 
Section 6.2.1 
• To quantify plasma PK parameters of PF- 
07081532 and total radioactivity following 
administration of a single oral dose of 
[14C]PF-07081532. 
• AUClast, Cmax, Tmax, and if data permit, AUCinf, t½, 
CL/F (PF-07081532 only), and Vz/F (PF-07081532 
only), to describe single oral dose PK in Period 1 of: 
• Total radioactivity in plasma; 
• PF-07081532 in plasma. 
PK 
Section 6.2.1 
• To quantify plasma PK parameters of 
[14C]PF-07081532, following 
administration of a single, IV, microdose 
of [14C]PF-07081532. 
• [14C]PF-07081532 parameters to describe IV 
plasma PK: AUClast, AUClast(dn), Cmax, Cmax(dn), 
Tmax, and if data permit, AUCinf, AUCinf(dn), t½, CL, 
Vss and MRT. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 6 of 24 
 
 
 
PK 
Section 6.2.2 
• To determine the absolute oral 
bioavailability (F) of PF-07081532 
following administration of a single oral 
dose of PF-07081532 compared to a single 
IV microdose of [14C]PF-07081532. 
• F computed from plasma AUCinf (if data permit, 
otherwise AUClast) of oral unlabeled PF-07081532 
in Period 2 and IV microdose of [14C]PF-07081532 
in Period 2. 
PK 
Section 6.2.3 
• To determine the fraction of dose absorbed 
(Fa) following administration of a single 
oral dose of [14C]PF-07081532. 
• Fa calculated from ratio of total urinary 
radioactivity following oral administration of 
[14C]PF-07081532 in Period 1 and IV 
administration of [14C]PF-07081532 in Period 2. 
Safety 
Section 6.6 
• To evaluate safety and tolerability of PF- 
07081532, administered as a single oral 
dose of [14C]PF-07081532 or a single oral 
dose of PF-07081532 followed by 
administration of a single IV microdose of 
[14C]PF-07081532. 
• Safety endpoints including physical examinations, 
adverse events, clinical laboratory measurements, 
vital signs, and ECG. 
Tertiary/Exploratory: : 
PK 
Section 6.3.1 
• To characterize cumulative rate of 
excretion of total radioactivity in urine and 
feces over time following administration of 
a single oral dose of [14C]PF-07081532. 
• Cumulative recovery of radioactivity in urine and 
feces, and both routes combined over time as a 
percentage of total radioactive dose administered. 
PK 
Section 6.3.2 
• To quantify plasma PK parameters of PF- 
07081532, following administration of a 
single oral dose of (unlabeled) PF- 
07081532. 
• Parameters to describe oral plasma PK following 
oral administration of PF-07081532 in Period 2: 
Cmax, Cmax(dn), Tmax, AUClast, AUClast(dn), and if data 
permit, AUCinf, AUCinf(dn), t½, CL/F and Vz/F. 
Other 
Section 6.3.3 
CCI 
Other 
Section 6.3.4 
 
There are no estimands for this study. 
 
2.3. Study Design 
C3991006 is a Phase 1, open-label, 2-period, fixed sequence study to characterize the 
metabolic profile and routes of excretion of oral [14C]PF-07081532 and to evaluate the 
absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-07081532 in healthy male 
participants. 
Participants will be screened for enrollment in this study within 28 days of dosing on Day 1 
of Period 1, to confirm that they meet the inclusion/exclusion criteria specified in Section 5 
of the protocol. The expected duration of participation from screening to follow-up will be 
approximately 8 weeks (minimum) to approximately 12 weeks (maximum). The overall study 
design is summarized in the schema below. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 7 of 24 
 
 
 
 
 
a. See Section 4.1 of the protocol for details on Period 1 discharge criteria. 
b. At least 21 days of washout is required between dosing in Period 1 and Period 2. 
c. 
In Period 2, participants will be discharged from the CRU on Day 7. 
 
 
Regimen in Period 1: An oral dose of 30 mg PF-07081532 containing approximately 
250 nCi [14C] (ie, radiolabeled PF-07081532, [14C]PF-07081532) will be administered 
within approximately 10 minutes of completion of a standard breakfast. 
Regimen in Period 2: An oral dose of 30 mg unlabeled PF-07081532 will be administered 
followed at approximate Tmax by an IV dose of 250 nCi [14C] in 100 µg of PF-07081532 
(ie, [14C]PF-07081532). The [14C]PF-07081532 IV dose will be administered as an infusion 
over approximately 15 minutes, starting at approximately 1 hour (Tmax) after the 
administration of the oral unlabeled PF-07081532 dose. Oral unlabeled PF-07081532 will 
be administered within approximately 10 minutes of completion of a standard breakfast. 
In Period 1, a sufficient number of participants will be admitted on Day -1 to the CRU to 
ensure that 6 participants are dosed on Day 1. Any participants who are prematurely 
withdrawn (or offer non-evaluable or partially evaluable data) will be replaced to ensure 
6 evaluable participants completing Period 1. In Period 2, participants who are prematurely 
withdrawn may be replaced at the discretion of sponsor. 
 
 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint(s) 
Urine, feces and vomitus samples will be collected according to the Schedule of Activities 
given in the protocol and will be analyzed for total radioactivity. 
3.1.1. Extent of Excretion (Period 1 Only) 
Urine, feces and vomitus samples will be collected according to the Schedule of Activities 
given in the protocol and will be analyzed for total radioactivity. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 8 of 24 
 
 
Extent of Excretion will be determined by recovery of total radioactivity excreted in urine 
and feces (and emesis, if applicable). Total recovery of radioactivity in urine and feces, and 
both routes combined, will be calculated as a percent of total oral radioactive dose 
administered. The percentage of the administered radioactivity excreted at each time interval 
and the total percent of dose excreted in urine and feces will be reported whenever possible. 
Note: the extent of Excretion analysis is summarized in this SAP for completeness only. 
Methods and results related to extent of Excretion will be detailed in a separate report and 
will be summarized within the Clinical Study Report (CSR). 
3.1.2. Metabolite Endpoints 
Plasma, urine and fecal samples collected in Period 1 will be analyzed for metabolites of 
PF-07081532. Major metabolites of PF-07081532 in plasma, urine and feces may be 
identified if possible. Contributions of parent and each major metabolite to total 
radioactivity recovered in urine and feces and to circulating radioactivity in plasma will be 
quantified. 
Results of the metabolic profiling analysis will be detailed in a separate report and will be 
summarized within the CSR. 
Note: Methods and results related to analysis of metabolites will similarly be detailed in a 
separate report provided by TNO. 
3.2. Secondary Endpoint(s) 
3.2.1. Plasma Pharmacokinetic Parameters 
Plasma samples for PK analysis will be collected according to the Schedule of Activities given in 
the protocol. 
• For Period 1, following a single oral administration of [14C]PF-07081532, oral PK 
parameters for total [14C] radioactivity will be derived from the concentration 
equivalent-time profiles, where appropriate. Additionally, PK parameters for 
PF-07081532 will be derived from the concentration-time profiles based on 
LC/MS/MS analysis of plasma samples. 
• For Period 2, following a single oral dose of unlabeled PF-07081532, PK parameters 
for PF-07081532 will be derived from the concentration-time profiles based on 
LC/MS/MS analysis of plasma samples (note that this reflects a tertiary endpoint and 
as such is also listed under Section 3.3). 
• For Period 2, following a single IV microdose dose of [14C]PF-07081532 at 1 hour 
post oral dose, IV plasma PK parameters of [14C]PF-07081532 will be derived from 
plasma radioactivity concentration-time profiles following chromatographic 
separation of [14C]PF-07081532. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
 
se of [ C}PF-07081532 ( 
14 
._ 
oral and IV administration), as data 
 ,. 
The following plasma PK parameters will be dete1mined using standard non-compartmental 
methods: 
Table 2. 
Summary of plasma PK Parameters to be calculated 
 
Parameter 
Analysis 
Scale 
After ornl dose of 
[14C)PF-07081532 
(Period 1) 
After IV dose of 
[14C)PF-07081532 
(Period 2) 
After oral dose of 
PF-07081532 
(Period 2) 
Total 
Radioactivity 
PF-07081532 
[14C)PF-07081532 
PF-07081532 
AUC1as1 
1n 
D 
D 
D 
D 
AUC1as1 (dn) 
1n 
NC 
NC 
D 
D 
AUCinf* 
1n 
D 
D 
D 
D 
AUCinf*(dn) 
1n 
NC 
NC 
D 
D 
Cmax 
1n 
D 
D 
D 
D 
Cma,ldn) 
1n 
NC 
NC 
D 
D 
Tmax 
R 
D 
D 
D 
D 
t112* 
R 
D 
D 
D 
D 
CL* 
1n 
NC 
NC 
D 
NC 
v..* 
1n 
NC 
NC 
D 
NC 
MRT* 
1n 
NC 
NC 
D 
NC 
CL/F* 
1n 
NC 
D 
NC 
D 
Vz/F* 
1n 
NC 
D 
NC 
D 
*=if data permits. Abbreviations: D=displayed with descriptive statistics as outlined in 
Table 3 in Section 6.2.1; dn=dose nonnalized; ln=natural-log transfo1med; NC= not 
calculated; R=raw (untransfo1med); 
Actual PK sampling times will be used in the derivation of PK parameters, defined relative to 
the time of the oral dose for the parameters referring to oral dosing and relative to the sta1t of 
the 15-minute IV infusion for the pai·ameters referring to IV dosing. Actual administered 
[14C] doses will be used for the total [14C] radioactivity and [14C]PF-07081532 PK parameter 
calculations. 
 
Plasma PK pai·ameters above will be listed and summai-ized descriptively as appropriate, by 
analyte (total [14C], unlabeled PF-07081532, and [14C]PF-07081532) and route of 
administration (oral or IV), as specified in Section 5.2 
Absolute bioavailability (F) will additionally be calculated as the ratio of adjusted geometric 
means of dose-no1malized AUCinf (if data pe1mit, othe1wise AUC1ast(dn)) following oral, 
unlabeled, PF-07081532 and intravenous, [14C]PF-07081532 which is equivalent to the 
following equation: 
F = [PF-07081532_AUCpJPF-07081532_AUC;v]*[PF-07081532_Dose;v/PF- 
07081532_Dosepo] 
3.2.2. Urine Pharmacokinetic Parameter 
The following urine parameters will be calculated following single dose administration of a 
microtracer do 
permit. 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 10 of 24 
 
 
Residual [14C] levels from Period 1 will be accounted for using an appropriate method, 
based on AMS principles and methodology. 
 
Parameter 
Definition 
Method of Determination 
Total [14C]_Urine_PO 
Total cumulative radioactivity 
excreted into urine from time zero 
up to the time of last measurable 
concentration following oral 
administration of [14C]PF- 
07081532 (Period 1 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for each 
collection interval 
Total [14C]_Urine_PO_Trunc* 
Total cumulative radioactivity 
excreted into urine from time zero 
up to Day 7 (matching duration of 
Period 2 urine collection up to 
discharge) following oral 
administration of [14C]PF- 
07081532 (Period 1 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for each 
collection interval 
Total [14C]_Urine_IV 
Total cumulative radioactivity 
excreted into urine from time zero 
up to the time of last measurable 
concentration following IV 
administered [14C]PF-07081532 
microdose (Period 2 only) 
Directly from observed [14C] data, 
calculated as sum of [14C urine 
concentration × sample volume] for each 
collection interval 
% [14C]_Urine_PO 
% of radioactivity in the urine 
following oral administration, 
expressed as a percent of the 
radioactive dose administered 
(Period 1 only) 
(Total [14C]_Urine_PO/[14C] Dosepo) *100 
where, 
[14C] Dosepo is orally administered actual 
dose of [14C]PF-07081532 
% [14C]_Urine_PO_Trunc* 
% of radioactivity in the urine up to 
Day 7 (matching duration of 
Period 2 urine collection up to 
discharge) following oral 
administration, expressed as a 
percent of the radioactive dose 
administered (Period 1 only) 
(Total [14C]_Urine_PO_Trunc/[14C] 
Dosepo) *100 
where, 
[14C] Dosepo is orally administered actual 
dose of [14C]PF-07081532 
% [14C]_Urine_IV 
% of radioactivity in the urine 
following IV administration 
expressed as a percent of the 
radioactive dose administered 
(Period 2 only) 
(Total 14C _Urine_IV/[14C] Doseiv) *100 
where, 
[14C] Doseiv is [14C] IV administered actual 
dose of [14C]PF-07081532 
*_Trunc parameters may not be calculated and reported if not applicable (ie, no participant is discharged after Day 7 
in Period 1). 
 
Fa will be estimated as the ratio of adjusted geometric means of the % of administered 
radioactive dose excreted into urine following oral and IV administration of 
[14C]PF-07081532 in Periods 1 and 2, respectively. 
Urine radioactivity up to Day 7 will be used for Period 1 to match the duration of Period 2 
urine collection up to discharge: 


Protocol C3991006 (PF-07081532) 
Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 11 of 24 
 
 
CCI 
Fa = [% [14C]_Urine_PO_Trunc/% [14C]_Urine_IV] 
For IV administration of [14C]PF-07081532, the weight of dose administered and solution 
density, in conjunction with the dosing solution concentration data will be used to determine 
the exact dose administered, where formulas will be included in the analysis and reporting 
plans. This actual dose will be used for PK parameter calculations. 
For oral administration of [14C]PF-07081532, the weight of drug powders added to each 
individual dosing container will be used along with specific activity and chiral potency of the 
drug powder to determine exact dose administered, where formulas will be included in the 
analysis and reporting plans. This actual dose will be used for PK parameter calculations. 
3.3. Other Endpoint(s) 
3.3.1. Cumulative Rate of Excretion (Period 1) 
See Section 3.1.1. 
3.3.2. Pharmacokinetics Parameters (Oral Unlabeled PF-07081532 - Period 2) 
See Section 3.2.1. 
 
3.4. Baseline Variables 
Not applicable. 
3.5. Safety Endpoints 
Assessment of treatment emergent AEs, clinical laboratory abnormalities, vital signs, ECG 
parameters. 
An adverse event is considered treatment emergent (TEAE) relative to a given treatment if: 


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• the event starts during the effective duration of treatment (i.e. starting on or after the 
dose of PF-07081532 but before this dose plus lag time) 
The effective duration of treatment is determined by the lag time. Any event occurring within 
the lag time is attributed to the corresponding treatment. The lag time is defined by the Pfizer 
Standard of 365 days post last dose of IP. 
Events that occur in a non-treatment period (for example, Washout or Follow-up) will be 
counted as treatment emergent and attributed to the most recent treatment taken. 
 
A 3-tier approach for summarizing AEs will not be used due to the low number of 
participants planned to be recruited. 
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters): 
• adverse events, 
• laboratory data, 
• vital signs data, 
• ECG results. 
For laboratory, vital signs and ECG data, the baseline measurement is the planned last pre- 
dose measurement taken on Day -1 or Day 1 (as applicable) in each period. 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) 
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures. 
For purposes of analysis, the following analysis sets are defined: 
 
Participant Analysis 
Set 
Description 
Enrolled 
“Enrolled” means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process and 
assignment to and dosing with study intervention. 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. 


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Participant Analysis 
Set 
Description 
Safety analysis set 
All participants assigned to study intervention and who take at 
least 1 dose of study intervention. 
Extent of excretion 
analysis set 
In Period 1, extent of excretion population will be defined by 
evaluable participants who have received 1 dose of 
[14C]PF-07081532 and who have complete total radioactivity 
concentration (urinary and fecal) data and who had no protocol 
deviations that may have affected the extent of excretion analysis. 
PK concentration set 
The PK concentration population for PF-07081532 is defined as 
all participants dosed with PF-07081532 or [14C]PF-07081532, 
who have at least one PF-07081532 concentration. 
The PK concentration population for [14C]PF-07081532 is 
defined as all participants dosed with [14C]PF-07081532, who 
have at least one [14C]PF-07081532 measurement. 
The PK concentration population for total [14C] is defined as all 
participants dosed with [14C]PF-07081532, who have at least 
one total [14C] measurement. 
PK parameter set 
The PK parameter analysis population for PF-07081532 is 
defined as all participants dosed with PF-07081532 or 
[14C]PF-07081532 who have at least one of the PF-07081532 PK 
parameters of interest. 
The PK parameter analysis population for [14C]PF-07081532 is 
defined as all participants dosed with [14C]PF-07081532 who 
have at least one of the [14C]PF-07081532 PK parameters of 
interest. 
The PK parameter analysis population for total [14C] is defined 
as all participants dosed with [14C]PF-07081532 who have at 
least one of the total [14C] PK parameters of interest. 
Urine PK parameter 
analysis population 
The urine PK parameter analysis population for total radioactivity 
excreted into urine is defined as all participants dosed who have 
at least one of the urine [14C] parameters of interest. 
CCI 
5. GENERAL METHODOLOGY AND CONVENTIONS 
5.1. Hypotheses and Decision Rules 
There is no statistical hypothesis testing planned for this study and no statistical decision 
rules will be applied. 


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5.2. General Methods 
For all safety outputs produced, the following treatment labels (or similar) will be used: 
• [14C]PF-07081532 30 mg oral 
• Unlabeled PF-07081532 30 mg oral & [14C]PF-07081532 100 µg IV 
For all PK outputs produced, the following analyte labels (or similar) related to the above 
treatments will be used: 
• 
Related to “[14C]PF-07081532 30 mg oral” treatment from Period 1: 
o PF-07081532 (Period 1) 
o Total (14C) (Period 1) 
• 
Related to “Unlabeled PF-07081532 30 mg oral & [14C]PF-07081532 100 µg IV” 
treatment from Period 2: 
o PF-07081532 (Period 2) 
o [14C]PF-07081532 (Period 2) 
 
5.2.1. Analyses for Continuous Endpoints 
Unless otherwise stated, continuous variables will be presented using summary statistics: 
number of observations, arithmetic mean, standard deviation, median, minimum and 
maximum values. 
5.2.2. Analyses for Categorical Endpoints 
Categorical variables will be presented using summary statistics: number of observations and 
percentages. 
5.2.3. Mixed Model for Continuous Endpoints 
A mixed effect model with treatment as a fixed effect and participant as a random effect will 
be used. Estimates of the adjusted (least squares) mean differences (Test-Reference) and the 
corresponding 90% confidence interval will be obtained from the model. The adjusted mean 
differences and 90% confidence intervals for the differences will be exponentiated to provide 
estimates of the ratio of adjusted geometric means (Test/Reference) and 90% confidence 
interval for the ratio. 
 
The mixed effects model will be implemented using SAS Proc Mixed, with REML 
estimation method and the Kenward-Roger degrees of freedom algorithm. 
Example code is shown in Appendix 1. 
 
Residuals from the models 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 (where studentized residuals are greater than 3 or less 
than -3) then the effect of these on the conclusions may 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 if applicable. 


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5.3. Methods to Manage Missing Data 
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied. 
 
In all PK 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. 
 
In PK summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if one of the following cases is true: 
1. A concentration has been collected as ND (i.e. not done) or NS (i.e. 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. 
Participants who experience events that may affect their PK profile (e.g. lack of compliance 
with dosing or vomiting) 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. 
5.3.1. Plasma Pharmacokinetic Parameters 
Actual PK sampling times will be used in the derivation of plasma PK parameters. 
 
If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (i.e. not calculated). (Note that NC values will not be generated beyond 
the day that a participant discontinues.) 
 
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular treatment group/analyte with ≥3 evaluable measurements. 
 
Note: If N <3 evaluable measureemnts, only mean, median and range will be provided in 
summary statistics. 
 
For statistical analyses (i.e. mixed effect model), 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 plasma PK parameter (due for 
example to an unexpected event such as vomiting before all the compound is adequately 


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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. 
6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoint(s) 
6.1.1. Extent of Excretion (Period 1 Only) 
Radioactivity excreted in urine and/or feces will be reported as the percentage of the 
administered radioactivity excreted at each time interval, cumulatively through that interval 
and the total percent of dose recovered in urine, feces, and/or emesis (if any). 
Percent recovery and cumulative recovery of total radioactivity in urine, feces and emesis (if 
any) will be determined based on total administered dose. 
Note: While the total percentage of dose excreted is the primary endpoint, the percentage of 
the administered radioactivity excreted at each time interval and cumulatively through that 
interval are tertiary endpoints. 
Individual participant and median data profiles for total radioactivity will be graphically 
presented for the cumulative recovery of radioactivity in urine, feces and their combination 
in Period 1 only. Emesis, if any, will be collected during 24 hours post oral dose, but these 
participants will not necessarily be excluded from analysis. The total recovery of 
radioactivity in urine, feces (and emesis, if any) and their combination will be listed and 
summarized for Period 1 only. 
 
Primary results of the extent of excretion (i.e., radioactivity in urine, feces, and vomitus if 
observed) will be detailed in a separate report provided by ICON and will be summarized 
within the CSR. 
6.1.2. Metabolic Profiling and Metabolite Identification 
Results of the metabolic profiling analysis will be detailed in a separate report and will be 
summarized within the CSR. 
6.2. Secondary Endpoint(s) 
6.2.1. Plasma PK parameters of PF-07081532 and total radioactivity in Period 1 and 
[14C]PF-07081532 in Period 2 
Plasma PK parameters of PF-07081532 (Period 1), total radioactivity (Period 1) and 
[14C]PF-07081532(Period 2), as described in Section 3.2.1, will be listed and summarized 
descriptively by analyte, route of administration (IV vs. Oral) and treatment for participants 
in the PK analysis set (as defined in Section 4) using nominal sampling times. Missing values 
will be handled as detailed in Section 5.3 
The relevant plasma PK parameters for each analyte, route of administration and treatment 
(see Section 3) will be summarized as specified in the table below: 


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ctual time post-
 time plots for analytes PF 
Table 3. 
Summary statistics to be produced for Plasma PK Parameters 
 
Parameter 
Summary Statistics 
AUC1ast, AUCinf, AUC1ast(dn), 
AUCini(dn), Cmax, Cmax(dn), 
MRT, CL/F (oral), Vz/F 
(oral), CL (IV) and Vss(IV) 
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum, geometi·ic mean and geometi·ic 
cv%. 
Tmax 
N, median, minimum, maximum. 
t112 
N, arithmetic mean, median, cv%, standard deviation, 
mm1mum, maxnnum. 
Box and whisker plots for individual participant parameters (AUCinf(dn), AUClast(dn), and 
Cmax(dn) be presented and overlaid with geomeu-ic means. 
Suppo1ting data from the estimation oft½ and AUCinfwill be listed by analyte: tenninal 
phase rate constant (ke1); goodness of fit statistic from the log-linear regression (i2); the 
percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number oftime 
points used in the estimation ofke1. These data may be included in the clinical study repo1t. 
The following summaries will additionally be presented for the plasma concenti·ation data of 
the analytes using the PK Concenti·ation Set (as defined in Section 4): 
- 
a listing of all concenti·ations s01ted by paiticipant ID and nominal time post-dose for 
each analyte, route of adminisu-ation and ti·eatment, separately. The concenti·ation 
listing will also include the actual times. Deviations from the nominal time will be 
given in a sepai·ate listing. 
- 
a summaiy of concenu-ations by each nominal time post-dose (produced sepai·ately 
for each analyte), where the set of statistics will include n, mean, median, standard 
deviation, coefficient of vai·iation (cv), minimum, maximum and the number of 
concenu-ations above the lower limit of quantification. 
- 
 median concentration time plots (on both lineai·and semi-log scales) against nominal 
time post-dose by analyte for PF-07081532 (Period 1) and total radioactivity (Period 
1) only. The concenu-ation time plots for these analytes will be presented together on 
the same plot. 
- 
median concentration time plots (on both lineai·and semi-log scales) against nominal 
time post-dose by analyte and route of adminisu-ation for PF-07081532 (Period 2) and 
[14C]PF-07081532 (Period 2) only, where both have been dose-no1malized (by oral 
and IV dose, respectively). The dose-no1malization will be calculated by 
prograinming using raw concenti·ations and the actual doses administered. The 
concenu-ation time plots for these analytes will be presented together on the same 
plot. 
- 
 individual concentration time plots by analyte (on both lineai·and semi-log scales) 
against actual time post-dose (there will be separate spaghetti plots for each analyte 
per scale). 
individual concenti·ation time plots by paiticipant (on both lineai·and semi-log scales) 
against a 
-07081532 


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(Period 1) and total radioactivity (Period 1) will be presented together on the same 
plot. In a separate figure, the analytes PF-07081532 (Period 2) and [14C]PF-07081532 
(Period 2), where both have been dose-normalized (by programming using raw 
concentrations and the actual doses administered), will be presented together on the 
same plot. 
The nominal PK sampling time will be used for summary statistics and relevant median 
plots, whereas for individual participant plots by time, the actual PK sampling time will be 
used. 
6.2.2. Absolute Bioavailability 
All listings and analyses of absolute bioavailability will use the PK Parameter population (as 
defined in Section 4). 
Natural log transformed AUCinf(dn) (if data permit, otherwise AUClast(dn)) from Period 2 
will be analyzed using a mixed effect model (as defined in Section 5.2.3) with treatment as a 
fixed effect and participant as a random effect. Estimates of the adjusted (least squares) 
mean differences (Test-Reference) and the corresponding 90% confidence interval will be 
obtained from the model. The adjusted mean differences and 90% confidence intervals for 
the differences will be exponentiated to provide estimates of the ratio of adjusted geometric 
means (Test/Reference) and 90% confidence interval for the ratio where IV 
[14C]PF-07081532 is the reference formulation and unlabeled oral PF-07081532 is the test 
formulation. 
Individual oral bioavailability (F) values (as defined in Section 3.2.1) will also be listed. 
A box plot of the individual AUCinf(dn) (if data permit, otherwise AUClast(dn)) values used to 
calculate such bioavailability from Period 2 only will be produced with a separate box and 
whiskers for each analyte and treatment (IV vs PO), which will include the geometric means 
for each analyte overlaid. 
The above will be conducted for AUClast(dn) regardless, but will only be formally reported if 
AUCinf(dn) data do not permit sufficient estimation of F. 
6.2.3. Fraction Absorbed 
All listings and analyses of absolute bioavailability will use the PK Parameter population (as 
defined in Section 4). 
Total radioactivity excreted in urine as absolute values (Total 14C_Urine_PO and Total 
14C_Urine_IV) and expressed as percent of [14C] dose (% 14C_Urine_PO and % 
14C_Urine_IV) as defined in Section 3.2.2 will be listed and summarized descriptively by 
period. Summaries will include: N; arithmetic mean; median; cv%; standard deviation; 
minimum; maximum; geometric mean; and geometric cv%. 
Natural log transformed % [14C]_Urine_PO_Trunc (if data permit) from Period 1 
and % [14C]_Urine_IV (if data permit) from Period 2 will be analyzed using a mixed effect 


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CCI 
model (as defined in Section 5.2.3) with treatment as a fixed effect and participant as a 
random effect. 
Estimates of the adjusted (least squares) mean differences (Test-Reference) and the 
corresponding 90% confidence interval will be obtained from the model. The adjusted mean 
differences and 90% confidence intervals for the differences will be exponentiated to provide 
estimates of the ratio of adjusted geometric means (Test/Reference) and 90% confidence 
interval for the ratio where IV [14C]PF-07081532 is the reference formulation and oral 
[14C]PF-07081532 is the test formulation. 
The individual mean fraction absorbed (Fa) values (as defined in Section 3.2.2) will also be 
listed. 
A box plot of the individual values of % 14C_Urine_PO_Trunc and % 14C_Urine_IV in 
Periods 1 and 2, respectively, will be produced with a separate box and whiskers for each 
period, which will include the geometric means for each period overlaid. 
Absolute radioactivity concentration levels excreted in urine at each time interval for both 
periods will also be listed only. 
6.3. Other Endpoint(s) 
6.3.1. Cumulative recovery of radioactivity excreted in Urine, Feces and Combined 
Cumulative recovery of radioactivity excreted in urine, feces and both routes combined, 
expressed as a percentage of the administered dose of [14C]PF-07081532 up to and including 
each time interval, will be listed, summarized, plotted and detailed in a separate report 
provided by ICON and will be summarized within the CSR as part of the extent of Excretion 
analysis. 
6.3.2. Plasma PK parameters of PF-07081532 in Period 2 
Plasma PK parameters of PF-07081532 in Period 2 as described in Section 3.2.1 will be 
listed and summarized descriptively (as outlined in Table 3 in Section 6.2.1) for participants 
in the PK analysis set (as defined in Section 4). Missing values will be handled as detailed in 
Section 5.3. 
 
A similar set of outputs as provided in Section 6.2.1 will be produced for the individual 
plasma concentration data of PF-07081532 in Period 2 PK Concentration Set (as defined in 
Section 4). 
 


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CCI 
 
 
 
6.3.5. Banked Biospecimens 
Banked biospecimens will be collected and retained for future analyses, but will not be 
analyzed specifically for this study and will not be included in the CSR. 
6.4. Subset Analyses 
No subset analyses will be performed. 
6.5. Baseline and Other Summaries and Analyses 
Data will be reported in accordance with the sponsor reporting standards. 
6.5.1. Baseline Summaries 
Demographics data (age, gender, race, ethnicity, weight, body mass index and height) will be 
summarized as outlined in Section 5.2.1 and Section 5.2.2 as applicable for all participants. 
6.5.2. Study Conduct and Participant Disposition 
Participant evaluation groups will show end of study participant disposition by treatment and 
will show which participants were analyzed for pharmacokinetics (plasma and urine, 
separately), taste assessment and for safety, which may not be produced in one table. 
Frequency counts and percentages will be supplied for participant discontinuation(s) by 
treatment. 
6.5.3. Concomitant Medications and Nondrug Treatments 
All prior and concomitant medication(s) as well as non-drug treatment(s) will be provided in 
listings. 
6.6. Safety Summaries and Analyses 
Any clinical laboratory, ECG, BP, and pulse rate abnormalities of potential clinical concern 
will be described. 


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No formal analyses are planned for safety data. 
The safety endpoints detailed in Section 3.5 will be listed and summarized in accordance 
with sponsor reporting standards based on the safety population (as defined in Section 4), 
with more details provided below. 
6.6.1. Adverse Events 
Adverse events will be summarized by treatment and overall in accordance with sponsor 
reporting standards. 
 
If applicable, subject discontinuations due to adverse events will be detailed and summarized. 
6.6.2. Laboratory Data 
Laboratory data will be listed and summarized by treatment and overall in accordance with 
sponsor reporting standards. Baseline is as defined in Section 3.5. 
6.6.3. Vital Signs 
Absolute values and changes from baseline in supine systolic and diastolic blood pressure 
and pulse rate will be summarized by treatment in accordance with sponsor reporting 
standards. 
Maximum absolute values and changes from baseline for vital signs will also be summarized 
descriptively by treatment using categories as defined in Appendix 2. Numbers and 
percentages of participants meeting the categorical criteria will be provided. All planned and 
unplanned post-dose time-points will be counted in these categorical summaries. All values 
meeting the criteria of potential clinical concern will be listed. 
6.6.4. Electrocardiograms (ECG) 
Absolute values and changes from baseline in QT interval, heart rate, QTcF interval, PR interval, 
and QRS interval will be summarized by treatment in accordance with sponsor reporting 
standards. 
 
Maximum absolute values and changes from baseline for QTcF interval, PR interval and 
QRS interval will also be summarized descriptively by treatment using categories as defined 
by Appendix 2. Numbers and percentages of participants meeting the categorical criteria will 
be provided. All planned and unplanned post-dose time-points will be counted in these 
categorical summaries. All values meeting the criteria of potential clinical concern will be 
listed. 
In addition, listings of participants with any single post-dose value >500 msec will also be 
produced for QTcF. 
 
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized. 


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7. INTERIM ANALYSES 
7.1. Introduction 
No formal interim analysis will be conducted for this study. As this is an open-label study, the 
sponsor will conduct unblinded reviews of the data during the course of the study for the purpose 
of safety assessment, early release criteria, facilitating PK modeling, and/or supporting clinical 
development. 
7.2. Interim Analyses and Summaries 
Not applicable. 
8. REFERENCES 
Not applicable. 


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9. APPENDICES 
Appendix 1. Example SAS Code for Mixed Model 
An example of the PROC MIXED code: 
proc mixed data=tab.pk; 
class treatment subject; 
model &var = treatment / ddfm=KR; 
random subject /subject=subject; 
lsmeans treatment/ diff cl alpha=0.1; 
run; 
Appendix 2. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern 
Categories for QTcF 
 
 
 
 
 
Categories for PR and QRS 
 
PR (ms) 
max. ≥300 
PR (ms) increase 
from baseline 
Baseline >200 
and max. 
≥25% increase 
Baseline ≤200 and 
max. ≥50% 
increase 
QRS (ms) 
max. ≥140 
QRS (ms) 
increase from 
baseline 
≥50% increase 
 
Categories for Vital Signs 
 
Systolic BP (mm Hg) 
min. <90 
Systolic BP (mm Hg) 
change from baseline 
max. decrease ≥30 
max. increase ≥30 
Diastolic BP (mm Hg) 
min. <50 
Diastolic BP (mm Hg) 
change from baseline 
max. decrease ≥20 
max. increase ≥20 
Supine pulse rate (bpm) 
min. <40 
max. >120 
 
Measurements that fulfill these criteria are to be listed in the report. 
Absolute value of 
QTcF (msec) 
 450 and 480 
>480 and 500 
>500 
Increase from baseline 
in QTcF (msec) 
 30 and 60 
>60 


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Appendix 3. List of Abbreviations 
Abbreviation 
Term 
AE 
adverse event 
AMS 
accelarated Mass Spectrometry 
AUC 
area under the curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated 
to infinity 
AUClast 
area under the concentration-time curve from time zero to the last 
measurable concentration 
BLQ 
below the limit of quantitation 
BP 
blood pressure 
Cmax 
maximum observed concentration 
CL 
clearance 
CL/F 
oral clearance 
CRF 
case report form 
CSR 
clinical study report 
CRU 
clinical research unit 
CV 
coefficient of variation 
dn 
dose normalized 
ECG 
electrocardiogram 
F 
oral bioavailability 
Fa 
fraction absorbed 
LLQ 
lower limit of quantitation 
ICH M3 (R2) MIST 
international confernec on harmonization M3 revision 2 for 
metabolites in safety testing 
IP 
investigational product 
IV 
intravenous 
LS/MS/MS 
liquid chromatography with tandem mass spectrometry 
MRT 
mean residence time 
N/A 
not applicable 
NC 
not calculated 
ND 
not done 
NS 
no sample 
PK 
pharmacokinetic(s) 
PO 
oral route 
QTcF 
corrected QT (Fridericia method) 
REML 
restricted maximum likelihood 
SAP 
statistical analysis plan 
SD 
standard deviation 
Tmax 
time of maximum concentration 
t½ 
half-life 
Vss 
steady state volume of distribution 
Vz/F 
apparent volume of distribution during terminal phase