Clinical trial NCT04857437
Conditions: Non-Alcoholic Fatty Liver Disease Liver Fibrosis
Sponsor: Pfizer
Start date: 2021-05-13; Completion date: 2021-09-17
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The study is planned as a 3 part design with investigator and participant blinded (sponsor-open), placebo controlled, randomized, dose escalation in Part 1 and Part 2; and a randomized, open label design, in Part 3 (if conducted).

Detailed description:

Arms: arm 1: Single, Escalating Doses of PF-07202954 or Placebo (Cohorts 1 and 2) arm 2: Repeated, Escalating Doses of PF-07202954 or placebo from Day 1 to Day 14, inclusive (Cohorts 3, 4, 5, 6 7, and optional Cohort 8) arm 3: Single dose of PF-07202954 with a high-fat/high-caloric meal and a single dose following an overnight fast of ≥10 hours
Interventions: intervention 1: PF-07202954 Repeat Dose intervention 2: PF-07202954 Single Dose intervention 3: Placebo
Intervention descriptions: intervention 1: 10, 30, 100, 300, 600, 1200 milligrams (mg) intervention 2: 10, 30, 100, 300, 600, 900, 1200 milligrams (mg) intervention 3: Matching Placebo

Protocol documents:
Prot_000.pdf: 
PF-07202954 
Protocol C4171001
FINAL Protocol Amendment 1, 01 December 2020 
PFIZER CONFIDENTIAL
Page 1
CLINICAL PHARMACOLOGY PROTOCOL
A PHASE 1, 3-PART, SPONSOR OPEN STUDY OF PF-07202954 IN HEALTHY 
ADULTS: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TO 
ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE (IN 
PART 1), AND REPEATED (IN PART 2), ESCALATING, ORAL DOSES ALONG 
WITH CONDITIONAL PART 3 OF RANDOMIZED, OPEN-LABEL ASSESSMENT 
OF EFFECT OF FOOD ON PF-07202954 EXPOSURE
Study Intervention Number:
PF-07202954
Study Intervention Name:
N/A
US IND Number:
147003
EudraCT Number:
2020-002121-28
Protocol Number:
C4171001
Phase:
1
Short Title: Multi-Part Study in Healthy Adults Evaluating Single- and 
Repeated-, Escalating, Oral Doses of PF-07202954 Plus Food Effect
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.


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PFIZER CONFIDENTIAL
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Amendment 
1
01 December
2020
This substantial amendment is making the following 
changes based on regulatory feedback from the US FDA
and FAMHP.
•
The PK stopping limit for AUC24 are revised to be more 
conservative: 
•
50% of exposure in male rats at NOAEL in 6 week 
toxicity study – ie, 18,400 ng•h/mL in Part 1 – refer 
to Table 1, Table 3, and Section 6.6.1;
•
10% of exposure in male rats at NOAEL in 6 week 
toxicity study – ie, 3,680 ng•h/mL in Part 2 with 
revision to this stopping limit to be considered, via a 
protocol amendment post formal interim analysis, 
based on observed data in Part 1 and Part 2 in this 
study - refer to Number of Participants in Protocol 
Synopsis, Table 1, Table 4, Section 6.6.1, and 
Section 9.5.
•
Participants with abnormal eGFR, as well as newly 
added UACR, UPCR will be disqualified – refer to 
exclusion criterion 7 in Section 5.2, and Table 12.
•
Participants will be disqualified based on revised, more 
conservative limits for ALT and AST (in Part 1 and 
Part 3) and Total bilirubin (all 3 Parts) – refer to 
exclusion criterion 7 in Section 5.2.
•
 
 
 
 
•
In Part 2, if the observed t½ of PF-07202954 is 
considerably longer than projected (in Part 1),
provisions added that mandate consideration of Day 14 
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PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
PK (along with Day 7) before initiation of dosing in the 
next cohort – refer to Section 6.6.1.
•
Added need for eye protection as part of caution for 
skin sensitivity to light and potential risk for sun burn –
refer to Table 1 and Section 5.3.3.
•
Cross reference to Table 1 added in Section 8.3.8 so as 
to acknowledge the potential risks based on completed 
nonclinical toxicity studies (with 1 or more of these 
potential risks classified as AESIs based on observed 
data from this study).
In addition, the following administrative changes are also 
being incorporated: 
•
Rationale for dosing with standard meal in Part 1 and 
Part 2
 
xpanded in Section 4.2.5 and couple of 
references to substantiate this added.
•
 
 
 
 
•
Definition of baseline, depending on endpoint has 
different predose nominal collection – note in Table 2
and Table 10 expanded to refer to SAP for definition of 
baseline for every single endpoint.
•
 
 
•
Given potential for CYP3A induction, use of estrogen
containing hormonal contraception and HRT was not 
permitted – this intent is clarified in Section 6.5.
•
While female participants of CBP need to use highly 
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PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
effective method of contraception with low user 
dependency, in female partners of male participants use 
of both low user dependent and use dependent options 
were intended to be permitted given their lower risk –
this intent clarified in Section 10.4.1 and Section 10.4.4.
Original 
protocol
02 October
2020
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.


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PFIZER CONFIDENTIAL
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................10
LIST OF FIGURES .................................................................................................................10
1. PROTOCOL SUMMARY...................................................................................................11
1.1. Synopsis ..................................................................................................................11
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities .............................................................................................14
2. INTRODUCTION ...............................................................................................................19
2.1. Study Rationale .......................................................................................................19
2.2. Background .............................................................................................................19
2.2.1. Nonclinical Pharmacology..........................................................................20
2.2.2. Nonclinical PK and Metabolism.................................................................21
2.2.3. Biopharmaceutics .......................................................................................21
2.2.4. Nonclinical Safety ......................................................................................22
2.3. Benefit/Risk Assessment.........................................................................................22
2.3.1. Risk Assessment.........................................................................................23
2.3.2. Benefit Assessment.....................................................................................26
2.3.3. Overall Benefit/Risk Conclusion................................................................26
3. OBJECTIVES AND ENDPOINTS.....................................................................................26
4. STUDY DESIGN.................................................................................................................27
4.1. Overall Design.........................................................................................................27
4.2. Scientific Rationale for Study Design.....................................................................28
4.2.1. Study Population.........................................................................................28
4.2.2. Rationale for Part 1.....................................................................................28
4.2.3. Rationale for Part 2.....................................................................................30
4.2.3.1. Assessment of Clinical Activity in Part 2 .................................31
4.2.4. Rationale for Part 3.....................................................................................31
4.2.5. Rationale for Dosing with Standard Meal in Part 1 and Part 2 ..................32
 
4.2.7. Rationale for Banked Sample Collection ...................................................32
4.3. Justification for Dose ..............................................................................................32
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4.3.1. Projected Human PK Parameters and Effective Human Dose ...................32
4.3.2. Human Exposure Limits.............................................................................33
4.3.3. Rationale for Dose Selection in Part 1........................................................33
4.3.4. Rationale for Dose Selection in Part 2........................................................34
4.3.5. Rationale for Dose Selection in Part 3........................................................36
4.4. End of Study Definition ..........................................................................................36
5. STUDY POPULATION......................................................................................................36
5.1. Inclusion Criteria.....................................................................................................36
5.2. Exclusion Criteria....................................................................................................37
5.3. Lifestyle Considerations..........................................................................................41
5.3.1. Meals and Dietary Restrictions...................................................................42
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................44
5.3.3. Activity .......................................................................................................44
5.3.4. Contraception..............................................................................................45
5.4. Screen Failures ........................................................................................................45
6. STUDY INTERVENTION..................................................................................................45
6.1. Study Intervention(s) Administered........................................................................45
6.1.1. Administration............................................................................................46
6.2. Preparation/Handling/Storage/Accountability ........................................................46
6.2.1. Preparation and Dispensing........................................................................47
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................48
6.3.1. Allocation to Study Intervention ................................................................48
6.3.2. Breaking the Blind – Part 1 and Part 2, only..............................................48
6.4. Study Intervention Compliance...............................................................................49
6.5. Concomitant Therapy..............................................................................................49
6.6. Dose Modification...................................................................................................50
6.6.1. Dose-Escalation and Stopping Rules..........................................................50
6.7. Intervention After the End of the Study..................................................................51
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................52
7.1. Discontinuation of Study Intervention ....................................................................52
7.1.1. ECG Changes..............................................................................................52


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7.1.2. Potential Cases of Acute Kidney Injury .....................................................52
7.2. Participant Discontinuation/Withdrawal from the Study........................................53
7.2.1. Withdrawal of Consent...............................................................................54
7.3. Lost to Follow up ....................................................................................................54
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................55
8.1. Efficacy Assessments..............................................................................................56
8.2. Safety Assessments .................................................................................................56
8.2.1. PEs..............................................................................................................57
8.2.2. Vital Signs ..................................................................................................57
8.2.3. 12-lead ECGs..............................................................................................58
8.2.3.1. Continuous Cardiac Monitoring by Telemetry – in Part 1, 
only....................................................................................................59
8.2.4. Clinical Safety Laboratory Assessments ....................................................60
8.2.5. Pregnancy Testing ......................................................................................60
8.3. Adverse Events and Serious Adverse Events..........................................................61
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......61
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................62
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................62
8.3.2. Method of Detecting AEs and SAEs ..........................................................62
8.3.3. Follow-up of AEs and SAEs.......................................................................62
8.3.4. Regulatory Reporting Requirements for SAEs...........................................62
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................63
8.3.5.1. Exposure During Pregnancy......................................................63
8.3.5.2. Exposure During Breastfeeding ................................................65
8.3.5.3. Occupational Exposure .............................................................65
8.3.6. Cardiovascular and Death Events...............................................................65
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................65
8.3.8. Adverse Events of Special Interest.............................................................66
8.3.8.1. Lack of Efficacy........................................................................66
8.3.9. Medical Device Deficiencies......................................................................66


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8.3.10. Medication Errors.....................................................................................66
8.4. Treatment of Overdose............................................................................................67
8.5. Pharmacokinetics ....................................................................................................67
8.5.1. Plasma for Analysis of PF-07202954 Concentrations – Parts 1, 2, 
and 3.................................................................................................................67
8.5.2. Plasma for Qualitative Metabolite Profiling - Part 2, only.........................68
8.5.3. Urine for Analysis of PF-07202954 Concentrations – Part 2, only............69
8.7. Genetics...................................................................................................................71
8.7.1. Specified Genetics ......................................................................................71
8.7.2. Banked Biospecimens for Genetics............................................................71
 
8.9. Immunogenicity Assessments.................................................................................75
8.10. Health Economics .................................................................................................75
9. STATISTICAL CONSIDERATIONS ................................................................................75
9.1. Statistical Hypotheses .............................................................................................75
9.2. Sample Size Determination.....................................................................................75
9.3. Analysis Sets ...........................................................................................................76
9.4. Statistical Analyses .................................................................................................77
9.4.1. General Considerations...............................................................................77
9.4.2. Primary Endpoint(s)....................................................................................77
9.4.3. Secondary Endpoint(s)................................................................................77
9.4.3.1. PK Analysis...............................................................................77
9.4.3.2. Statistical Methods for PK Data................................................79
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9.4.4.1. Analysis of Measures of Clinical Activity................................82
9.4.5. Safety Analyses ..........................................................................................82
9.4.5.1. Standard Safety Analyses..........................................................82
9.4.5.2. 12-lead ECG Interval Analyses.................................................82
9.4.6. Other Analyses............................................................................................83
9.5. Interim Analysis ......................................................................................................83
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............84
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS..........................................................................................................85
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............85
10.1.1. Regulatory and Ethical Considerations ....................................................85
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................85
10.1.2. Financial Disclosure .................................................................................86
10.1.3. Informed Consent Process........................................................................86
10.1.4. Data Protection .........................................................................................87
10.1.5. Dissemination of Clinical Study Data ......................................................87
10.1.6. Data Quality Assurance ............................................................................89
10.1.7. Source Documents....................................................................................90
10.1.8. Study and Site Start and Closure ..............................................................90
10.1.9. Publication Policy.....................................................................................91
10.1.10. Sponsor’s Qualified Medical Personnel .................................................92
10.2. Appendix 2: Clinical Laboratory Tests .................................................................93
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................95
10.3.1. Definition of AE .......................................................................................95
10.3.2. Definition of SAE.....................................................................................96
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................98
10.3.4. Reporting of SAEs..................................................................................100
10.4. Appendix 4: Contraceptive Guidance .................................................................102
10.4.1. Male Participant Reproductive Inclusion Criteria..................................102
10.4.2. Female Participant Reproductive Inclusion Criteria...............................102


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10.4.3. Woman of Childbearing Potential ..........................................................103
10.4.4. Contraception Methods...........................................................................104
10.5. Appendix 5: Genetics..........................................................................................106
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......107
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................109
10.8. Appendix 8: Abbreviations .................................................................................111
11. REFERENCES ................................................................................................................115
LIST OF TABLES
Table 1.
Potential Risks with PF-07202954 and C4171001 Design.......................23
Table 2.
Key Objectives and Endpoints in Study C4171001 .................................26
Table 3.
Predicted Human Exposures at Proposed Single Doses of 
PF-07202954.............................................................................................34
Table 4.
Predicted Human Steady-State Exposures at Proposed Repeated
Doses of PF-07202954 .............................................................................35
Table 5.
Study C4171001 - Part 1 - Randomization Scheme.................................41
Table 6.
Probable 90% CI with 80% coverage probability for Varying SDs 
and Sample Sizes – in Part 3.....................................................................76
Table 7.
Definition of the Analyses Sets in Study C4171001 ................................76
Table 8.
Plasma PK Parameters for Part 1 (Single, Escalating Doses) and 
Part 3 (Single Dose Food Effect, if Conducted) .......................................77
Table 9.
Plasma and Urine PK Parameters for Part 2 (Repeated Escalating 
Doses) .......................................................................................................78
Table 11.
Safety QTcF Assessment in Study C4171001..........................................83
Table 12.
All Planned Protocol-Required Safety-Related Laboratory Tests 
 of Clinical Activity in Study C4171001..........93
LIST OF FIGURES
Figure 1.
Overall Study Design - Part 1...................................................................13
Figure 2.
Overall Study Design - Part 2...................................................................14
Figure 3.
Overall Study Design - Part 3 [if conducted] ...........................................14
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1. PROTOCOL SUMMARY
1.1. Synopsis 
Short Title: Multi-Part Study in Healthy Adults Evaluating Single- and 
Repeated-, Escalating, Oral Doses of PF-07202954 Plus Food Effect
Rationale: The current clinical study is the first one proposed with PF-07202954. It is 
designed as a 3-part study in healthy adults. Part 1 will evaluate the safety, tolerability, and 
plasma PK 
 with administration of escalating, 
single, oral doses of PF-07202954 with a standard morning meal. Part 2 will evaluate safety, 
tolerability, and plasma and urine PK
 with 
repeated, escalating doses of PF-07202954 administered once daily with a standard morning 
meal for 14 days. Based on observed data from Part 1 and Part 2, Part 3 may be conducted to 
assess the effect of a high-fat/high-caloric meal versus a fasted state on the plasma PK of 
PF-07202954.
Objectives and Endpoints: The key objectives and endpoints for Part 1, Part 2, and Part 3 
(if conducted) of this study are summarized below –
Study 
Objectives
Endpoints 
Part 1
Primary 
To evaluate safety and tolerability 
of single, oral, escalating doses of 
PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants.
Following assessments over ≥10 days of each Period
and up to Day 30 ±2 days post last dose of study 
intervention –
• AEs;
• Clinical laboratory tests;
• Vital signs (including BP and pulse rate);
• Cardiac conduction intervals via 12-lead ECG.
Secondary 
To characterize the plasma PK
profile of PF-07202954 following 
administration of single, oral, 
escalating doses.
PK parametersa derived from plasma PF-07202954 
concentrations: 
• Cmax, Tmax, AUClast, AUCinf, t½, as data permit.
Part 2
Primary 
To evaluate safety and tolerability 
of repeated, oral, escalating doses 
of PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants with simple 
hepatic steatosis.
Following assessments over the duration of dosing and
up to Day 30 ±2 days post last dose of study 
intervention –
• AEs;
• Clinical laboratory tests;
• Vital signs (including BP and pulse rate);
• Cardiac conduction intervals via 12-lead ECG.
Secondary
To characterize the plasma and 
urine PK profiles of PF-07202954 
following administration of 
repeated, oral, escalating doses.
PK parametersa derived from plasma PF-07202954 
concentrations: 
• Single dose: Cmax, Tmax, AUCtau on Day 1;
• Repeated dose: 
•
Days 7 and 14 – Cmax, Tmax, AUCtau, as data 
permit;
•
Day 14 – t½ as data permit.
PK parametersa derived from urine PF-07202954 
concentrations on Day 14: Aetau, Aetau%, CLr.
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Study 
Objectives
Endpoints 
Part 3, if conducted
Primary 
To characterize the effect of a 
high-fat/high-caloric meal, 
compared to following an overnight 
fast, on plasma PK profile of 
PF-07202954 following 
administration of a single oral dose 
to healthy, adults.
PK parametersa derived from plasma PF-07202954 
concentration: 
Cmax, Tmax, AUClast, and AUCinf, as data permit.
Secondary
To evaluate safety and tolerability 
of a single, oral, dose of 
PF-07202954 administered with a 
high-fat/high-caloric meal compared 
to following an overnight fast.
Following assessments over ≥5 days of each Period and
up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG.
a.
For a complete definition of all PK parameters refer to Table 8 and Table 9.
NOTE: For all non-PK related endpoints, baseline is defined as the time-matched data obtained while on placebo 
[Part 1], 0H assessment on Day 1 or 0-12H or 0-24H assessment prior to 1st dose [Part 2], or 0H assessment on Day 1 in 
each Period [Part 3], unless otherwise specified in the SAP.
Overall Design: The study is planned as a 3-part design with investigator- and 
participant- blinded (sponsor-open), placebo-controlled, randomized, dose-escalation in 
Part 1 and Part 2; and a randomized, open-label design, in Part 3 (if conducted).
Number of Participants: In this study, participants can be randomized and receive the study 
intervention in 1 of the 3 parts, only. However, participants may be screened for more than 
1 part of the study. 
Part 1a
16 participants (8 per cohort)

6 active +2 placebo per dose level
Part 2a
Initially 30-40 participants with 10 participants per cohort (with potential to expand 
to 50 [minimum] to 60 [maximum] post formal IA and protocol amendment)

8 active +2 placebo per cohort
Part 3,a if conducted
8 (minimum) to 12 (maximum) participants

Sample size guided by observed variability in plasma PK in Part 1
a.
Participants prematurely withdrawn may be replaced at investigator discretion in consultation with the sponsor
A total of up to 88 unique participants are planned to be randomized in this study.
Note: "Enrolled" means a participant's agreement to participate in a clinical study following 
completion of the informed consent process and randomization. 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”.
Intervention Groups and Duration: In this study, the study interventions include 
PF-07202954 and placebo – both as extemporaneously prepared suspensions for oral 
administration. In Part 1 and Part 3, participants will receive single doses. In Part 2, 
participants will receive study intervention once daily for 14 days.


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DMC or Other Independent Oversight Committee: No
Statistical Methods: The sample size for Part 1 (single, escalating doses) and Part 2 
(repeated, escalating doses) has been chosen based on the need to minimize first exposure to 
humans of a new chemical entity and the requirement to provide adequate safety and 
toleration information at each dose level. For Part 3, a range of assumed variability estimates 
for plasma PK were used to derive the sample size that permits a sufficiently precise 
assessment with probable 90% CI for an effect size of 1.0 (ie, no change in exposure with 
and without food).
The data from the three Parts of this study will be analyzed separately and reported in a 
single CSR. All safety analyses will be performed on the Safety Analysis Set defined as all 
participants randomly assigned to study intervention and who consume at least 1 dose of 
study intervention. Safety data will be presented in tabular and/or graphical format and 
summarized descriptively, where appropriate. 
The PK parameters for PF‑07202954 following oral dose administration will be derived from 
the concentration‑time profiles. PK parameters and concentrations of PF‑07202954 will be 
descriptively summarized by dose and time, as appropriate.
1.2. Schema
The set-up of each of the 3 Parts of this study are summarized in Figure 1 (Part 1), 
Figure 2 (Part 2) and Figure 3 (Part 3).
Figure 1.
Overall Study Design - Part 1
Part 1: Sample size (N) = 16 participants
Randomized, double-blind (Sponsor-open), 4-period, inter-leaving, placebo-controlled, single, oral dose, escalating design
Screen to dosing on Day 1 in Period 1: maximum of 28 days
Inpatient stay in each Period: Day -1 to minimum of Day 4 (ie, 72H post dose)
In each Period, 6 participants randomized to receive PF-07202954, and 2 participants will receive matching-placebo with standard morning meal
Intervals of ≥x-days reflect number of days between dosing either between Cohorts (ie, ≥5-days) or within a given Cohort (ie, ≥10-days) 
On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention 
Cohort 1
(n=8) 
Cohort 2
(n=8) 
On-site
Follow-up visit 
Period 1
Dose #1
Period 2
Dose #3
Period 3
Dose #5
Period 1
Dose #2
Period 2
Dose #4
Period 3
Dose #6
Period 4
Dose #7
Period 4
Dose #8
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥10-days
≥10-days
≥10-days
≥10-days
≥10-days
≥10-days
Follow-up visit
Screen
Screen


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Figure 2.
Overall Study Design - Part 2
 Screen to Day 1: maximum of 28 days includes double confirmation of CAP ≥ 270 dB/m and VCTE < 7 kPa on FibroScan® on separate days
 Inpatient stay: Day -2 to Day 17 (19 consecutive days with 18 nights) 
 Baseline for safety (at 0H prior to dosing on Day 1), other markers of clinical activity (on Day -1), 
 In each cohort, 8 participants will be randomized to receive PF-07202954, and 2 participants will receive placebo
 Once-daily dosing to occur from Day 1 to Day 14, inclusive, with a standard morning meal
 On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention
Part 2: Sample size (N) = 50 in 1st planned 5 Cohorts and up to 60 including 1 optional Cohort of participants 
Randomized, double-blind (Sponsor-open), placebo-controlled, sequential, repeated, oral dose, escalating design
Cohort 3 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 4 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 5 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 6 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 7 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 8 
(n=10)
Optional 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Figure 3.
Overall Study Design - Part 3 [if conducted]
 Screen to Day 1 in Period 1: maximum of 28 days
 Inpatient stay: Continuous from Day -1 (in Period 1) to Day 4 (in Period 2) – a total of 10 days and 9 nights 
 On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention
Part 3 [if conducted]: Sample size (N) = ≤ 12 participants 
Randomized, open-label, 2-period, crossover, single oral dose of PF-07202954 administered with and without high-fat/high-caloric meal 
Period 1
Day 1
Period 2
Day 1
≥5-days
On-site 
Follow-up visit
Inpatient Stay
Follow-up visit
Screen 
1.3. Schedule of Activities
The SoA tables provide an overview of the protocol visits and procedures; refer to Section 8
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 here, in order to conduct evaluations or assessments required to 
protect the well-being of the participant.
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SoA - TABLE A. Part 1 – Single, Escalating Doses of PF-07202954/Placebo (Cohorts 1 and 2)
[refer to sub-sections in Section 8 for additional details]
Visit Identifier (for list of abbreviations refer to Section 10.8)
Screen
(≤28 
days)
Periods 1-4 [dosing separated by ≥10 days between Periods]
Follow-up
D/C
Day Identifier
-1
1
2
3
4
8±2 
daysa
30±2 
daysa
Hours Post Dose
N/A
0
0.5
1
2
3
4
5
8
12
16
24
36
48
72
Informed consent & demography 
x
Outpatient visit
x
x
Inpatient stay at CRU
x
→
→
→→→→→→→
→
→
→
→
x
Assessment of eligibility (& update on Day -1 in Period 1, only)
x
x
Medical history (with update on Day -1 in Period 1, only)
x
x
PE (plus height & body weight at Screen, only)b
x
x
Review alcohol/tobacco use & contraception use
x
x
x
x
xc
x
Review prior or concomitant (non-) drug treatments
x
x
x
x
x
Supine 12-lead ECGd
xd
x
x
x
x
x
x
x
x
x
x
x
x
xd
xd
Single, supine vital signs (includes BP and pulse rate at all times)
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
SAE and AE monitoring
x
x
→
→
→→→→→→→
→
→
→
→
→
x
x
x
Continuous cardiac telemetry monitoring
xe
x
→
→→→→→x
Standard mealsf
x
x
x
x
x
x
x
x
Blinded study intervention administration
xg
Blood Sampling [refer to Section 8.5 and Section 10.2] for –
Clinical laboratory tests (after ≥10 hour fast)
x
xh
x
x
x
x
Serum FSH [in females amenorrhoeic ≥12 months, only]
x
Serum pregnancy testing [in all females]
x
xh
x
x
Pre-specified PGx and Banked Prep D1.5 (Period 1 only)
x
Plasma PK [timepoints may be revised prior to dosing, if needed]
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Urine [refer to Section 10.2] for –
Spot sample for drug test
x
xh
Spot sample for urinalysis, UACR, UPCR (+microscopy, if needed)
x
xh
x
x
x
x
a.
Onsite Follow-up visit (8±2 days) and Follow-up telephone contact (30±2 days) to occur relative to last dose of investigational product in Period 4.
b.
Complete PE at Screen or upon admission in Period 1; otherwise, brief PE for findings at previous PE or new/open AEs only, at investigator discretion.
c.
Confirmation of appropriate contraception use, only.
d.
Single ECG at screen, on-site Follow-up visit, and D/C; triplicate supine 12-lead ECGs at all other timepoints.
e.
Baseline telemetry must be captured for ≥2 hours while participant is awake between admission on Day -1 and 0H on Day 1 of Period 1, only.
f.
Standard meals served at approximate clock times matching nominal time 0H, and at 5H, and 12H relative to dosing on Day 1, while inpatient.
g.
Following ≥10 hour overnight fast, dosing at approximately 8:00AM (±2H) to occur with standard morning meal provided ~30 mins prior to dosing at 0H.
h.
Results must be reviewed prior to dosing on Day 1 in each Period.
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SoA - TABLE B. Part 2 – Repeated, Escalating Doses of PF-07202954/Placebo (Cohorts 3, 4, 5, 6, 7, and optional Cohort 8)
[refer to sub-sections in Section 8 for additional details]
Protocol Activity
(for list of abbreviations refer to Section 10.8)
Screen
Baseline
All at 0H (prior to dosing) unless otherwise specified
Off-Drug
Follow-up
D/C
Study Day
-≤28 -≤2a
-2
-1
1
2
3
4
5
6
7
8
9
10
11
12
13
14 15
16
17
22±2b
44±2b
Informed consent & demography
x
Refer to SoA - Table C
Refer to SoA - Table C
Refer to SoA - Table C
Refer to SoA - Table C
Outpatient visit
x
x
x
Inpatient stay at CRU
x
→
→
→
→
→
→→→
→
→
→
→
→
x
Medical history (update)
x
x
x
Review alcohol/tobacco use & contraception use
x
x
x
x
x
Review prior or concomitant (non-) drug treatments 
x
x
x
PE (includes height at Screen)c
x
x
Body weight
x
x
x
x
x
FibroScan® (after ≥4 hour fast) 
x
xa,j
SAE and AE monitoring
x
x
x
→
→
→
→
→
→→→
→
→
→
→
→
x
x
x
x
Supine 12-lead ECGd
xd
xd
xd
xd
xd
xd
Single, supine vital signs (BP and pulse rate)
x
xe
xe
x
x
x
Standardized mealsf
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Blinded study intervention administrationg
x
x
x
x
x
x
x
x
x
x
x
Blood sampling [refer to Section 8.5 and Section 10.2] for:
Clinical laboratory tests 
xh
xa,j
xh
xh
xh
xh
xh
x
Serum FSH [females amenorrhoeic ≥12-months, only]
x
Serum pregnancy testing (in all females)
x
xj
x
x
x
Plasma PKi
x
x
xi
xi
xi
x
Urine sampling [refer to Section 10.2] for:
Urine drug test
x
xj
Urinalysis including microscopy, UACR, UPCR
x
x
x
x
x
x
x
x
a.
Separate from 1st Screen visit; can be conducted post ≥4 hour fast on Day -2 with double-confirmation on FibroScan® + LFTs before Day -2 
.
b.
Onsite Follow-up visit (8±2 days; ie, Day 22±2) and Follow-up telephone contact (30±2 days; ie, Day 44±2) to occur relative to last dose of investigational product.
c.
Complete PE at Screen or upon admission on Day -2; otherwise, brief PE for findings at previous PE or new/open AEs only, at investigator discretion.
d.
Single 12-lead ECG at screen, discharge, on-site Follow-up visit, and D/C; triplicate 12-lead ECGs at 2H (approximately Tmax) post dose on Days 4 and 10.
e.
Includes assessment at 0H plus an additional assessment at approximately 2H (approximately Tmax) post dose.
f.
Standard meals served at approximate clock times matching nominal time 0H, and at 5H, and 12H relative to dosing at 0H, each day while inpatient. 
g.
Following ≥10 hour overnight fast, dosing at approximately 8:00AM (±2H) to occur with standard morning meal provided ~30 mins prior to dosing at 0H.
h.
Collection following ≥10 hour overnight fast.
i.
PK samples collected prior to dose; in addition, on Day 15 [24H (SoA - Table C), 36H], Day 16 [48H], and Day 17 [72H] relative to dosing at 0H on Day 14.
j.
Results for these collections must be reviewed, by investigator before Day -2
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SoA - TABLE C. Part 2 – Repeated, Escalating Doses of PF-07202954/Placebo (Cohorts 3, 4, 5, 6, 7, and optional Cohort 8) – Days -1, 1, 7, 14 only 
[refer to sub-sections in Section 8 for additional details]
Hours Relative to Dosing at 0Ha
(for list of abbreviations refer to Section 10.8)
0
0.5
1
2
3
4
5
8
10
12
14
16
24b
Continued inpatient stay at CRU
→
→
→
→
→
→
→
→
→
→
→
→
→
SAE and AE monitoring
→
→
→
→
→
→
→
→
→
→
→
→
→
Body weight (Days 1, 7, 14)
x
Triplicate, supine 12-lead ECG (Days 1, 7, 14)
x
x
x
x
x
x
x
Single, supine vital signs (includes BP and pulse rate) - Days 1, 7, 14 
x
x
x
x
x
x
x
Standard mealsc
x
x
x
x
Blinded study intervention administration – Days 1, 7, 14d
x
Blood sampling [refer to Section 8.5, Section 8.8, and Section 10.2] for –
Clinical laboratory tests after ≥10 hour fast – Days 1, 7, 14
x
Pre-specified PGx and Banked Prep D1.5 – for DNA (Day 1, only) 
x
Serum extracellular vesicles (Days 1, 14)
x
Plasma PK – timepoints may be revised prior to dosing, if needed – Days 1, 7, 14
x
x
x
x
x
x
x
x
x
x
x
 
 
Urine sampling [refer to Section 8.5, Section 8.8, and Section 10.2] for –
Spot collection for urinalysis including microscopy, UACR, UPCR – Days 1, 7, 14
x
Pre-dose spot urine for PK - Urine blank on Day 1
x
24-hour interval for PF-07202954 PK (Day 14)
x
→
→
→
→
→
→
→
→
→
→
→
x
a.
On Day -1, nominal time to approximately match clock time of collection planned on Day 1 to permit time-matched comparison.
b. Equates to D2,0H (on Day 1), D8,0H (on Day 7), and D15,0H (on Day 14) – refer to Table B for other procedures on these days.
c.
Standard meal served ~30 mins prior to dosing at 0H plus at 5H, and 12H relative to approximate clock times matching dosing on Day 1.
d. Following ≥10 hour overnight fast, dosing at approximately 8:00AM (±2H) to occur with standard morning meal.
e.
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SoA - TABLE D. Part 3 (if Conducted) – Food Effect (Periods 1 & 2, inclusive) – [refer to sub-sections in Section 8 of additional details]
Visit Identifier [for abbreviations refer to Section 10.8]
Screen
(≤28 days)
Periods 1 and 2 [dosing separated by 5 days between Periods]
Procedures at 0H (prior to dosing) unless otherwise specified
Follow-up
D/C
Day Identifier
-1
1
2
3
4
8±2 
daysa
30±2 
daysa
Hours Post Dose
N/A
0
0.5
1
2
3
4
5
8
12
16
24
36
48
72
Informed consent & demography
x
Outpatient visit
x
x
Inpatient stay at CRU 
x












x
Assessment of eligibility
x
xb
Medical history
x
xb
PE (including height & body weight at Screen, only)c
x
xb
x
x
Review alcohol/tobacco use & contraception use
x
xb
xb
x
xd
x
Review prior or concomitant (non-) drug treatments
x
xb
x
x
x
Single, supine 12-lead ECG
x
x
xe
x
x
x
Single, supine vital signs (includes BP and pulse rate)
x
x
xe
x
x
x
SAE and AE monitoring
x
x













x
x
x
Standard mealsf
x
x
x
x
x
x
x
High-fat/high-caloric meal
xg
Open-label study intervention administration
xg
Blood Sampling [refer to Section 8.5 and Section 10.2] for –
Clinical laboratory tests [after 4 hour fast]
x
xh
x
x
x
x
Serum FSH [in females amenorrhoeic 12-months, only]
x
Serum pregnancy testing (in all females)
x
xh
xb
x
x
Pre-specified PGx and Banked Prep D1.5 (Period 1 only)
x
Plasma PK [nominal times may be revised prior to P1D1]
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Urine Sampling [refer to Section 10.2] for –
Urine drug test
x
xb,h
Urinalysis, UACR, UPCR (and microscopy, if needed)
x
xh
x
x
x
x
a.
On-site Follow-up visit (8±2 days) and Follow-up telephone contact (30±2 days) to occur relative to last dose of study intervention in Period 2.
b.
Procedures to be completed upon admission in Period 1; plus, upon discharge in Period 2, when denoted.
c.
Complete PE at either Screen or upon admission in Period 1; otherwise, brief PE for findings at previous PE or new/open AEs only, at investigator discretion.
d.
Confirmation of appropriate contraception use, only.
e.
Collection to occur at Tmax post dose, as observed in Part 1.
f.
Meals served at approximate clock times matching nominal time 0H (on non-dosing days while inpatient), 5H, and 12H relative to dosing on Day 1.
g.
Dosing at 8:00AM (±2H) in both Periods; as dictated by randomization scheme, dosing to occur with either high-fat/high-caloric meal (ie, provided ~30 mins prior to dosing 
at 0H and expected to be completed ~10 mins prior to dosing) or with water following an overnight fast of 10 hours.
h.
Results must be reviewed, by investigator, prior to dosing on Day 1.


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2. INTRODUCTION
DGATs catalyze the terminal step in TG synthesis, specifically the esterification of a fatty 
acid with DAG, resulting in the formation of TG.1 In mammals, 2 structurally unrelated 
DGAT enzymes (DGAT1 and DGAT2) have been characterized. DGAT1 is highly expressed 
in the intestine and plays a central role in fat absorption2 whereas DGAT2 is highly 
expressed in liver and adipose.3 DGAT2i is postulated to decrease hepatic TG synthesis and 
hepatic lipid burden in NAFLD and NASH. Based on observations in nonclinical studies 
conducted, it is hypothesized that DGAT2i will impact both physiological drivers 
contributing to NASH via direct inhibition of liver TG synthesis, as well as adaptive 
responses leading to reduction in hepatic DNL.
PF-07202954 is a potent and selective, orally administered, DGAT2i demonstrating greater 
than 4500-fold selectivity over related acyltransferases. It is being developed for the 
treatment of NASH with liver fibrosis. 
2.1. Study Rationale 
The current clinical study is the first one proposed with PF-07202954. It is designed as a 
3-part study in healthy adults. Part 1 will evaluate the safety, tolerability, and plasma PK of 
PF-07202954 with administration of escalating, single, oral doses of PF-07202954 with a 
standard morning meal. Part 2 will evaluate safety, tolerability, and plasma and urine PK as 
well as markers of clinical activity, in adults with simple hepatic steatosis, upon repeated, 
escalating doses of PF-07202954 administered once daily with a standard morning meal for 
14 days. Based on observed data from Part 1 and Part 2, assessment of the effect of a 
high-fat/high-caloric meal versus a fasted state on the plasma PK of PF-07202954 may be 
conducted in Part 3.
2.2. Background 
The World Gastroenterology Organization has indicated that NAFLD and NASH are now the 
number one cause of liver disease in Western countries as the prevalence of NAFLD has 
doubled during last 20 years, while the prevalence of other chronic liver diseases has 
remained stable or even decreased.4 NASH is diagnosed clinically by liver biopsy 
demonstrating steatosis, inflammation, and cytological ballooning of liver hepatocytes, often 
with varying degrees of fibrosis. NASH progresses with increasing severity of fibrosis, with 
cirrhosis developing in a subset of patients5 and a common complication of cirrhosis being 
HCC.6 NASH is a subset of NAFLD (defined as presence of ≥5% hepatic steatosis in the 
absence of other liver disease etiologies) that is associated with increased all-cause mortality, 
cirrhosis and end-stage liver disease, increased cardiovascular mortality, and increased 
incidence of both liver-related and non-liver related cancers.7
In a meta-analysis, the global prevalence of NAFLD was estimated at 25%, with the 
prevalence of NASH in the subset with biopsy-proven NAFLD assessed at 59%.5 The 
majority of the population with NAFLD has simple steatosis which has, in general, a benign 
clinical course. A proportion of participants with NAFLD progress to having hepatocellular 
ballooning and lobular inflammation, taking close to a decade to progress from 1 stage to the 


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next and 30-40 years to develop cirrhosis; however, a smaller subset of participants progress 
very rapidly (within 10 years) to liver cirrhosis from NAFLD.7 Patients with NASH may be 
asymptomatic or have non-specific symptoms such as fatigue, despite having significant 
disease on liver biopsy and associated risk for progression to cirrhosis and liver-related 
mortality. The 5-year (67%) and 10-year (38%) survival rates in patients with NASH is 
significantly different than in those with NAFLD. The pooled liver-specific and overall 
mortality incidence rate estimates among those with NAFLD were calculated at 0.8 and 
15.4, respectively, per 1,000 person-years. In contrast, amongst the population with NASH, 
the incidence rate estimates were 11.8 (liver-specific) and 25.6 (overall) mortality.7
Elevated rates of hepatic DNL have been reported to be a distinctive characteristic of 
NAFLD.8 Clinically, those with elevated liver fat showed a more than 3-fold increase in the 
rate of hepatic DNL relative to participants with normal liver fat, but no differences between 
the groups were detected in adipose FFA flux or in production of VLDL from FFAs. 
Consequently, when comparing the absolute sources of FA incorporated into VLDL-TG, 
elevated hepatic DNL was the only source significantly increased in participants with high 
liver fat.8 Hepatic DGAT2 deficiency reduces diet-induced hepatic steatosis without 
increasing inflammation or fibrosis in mice.9 This supports development of DGAT2 
inhibitors as a therapeutic strategy for treating NASH with liver fibrosis and preventing 
downstream consequences.
2.2.1. Nonclinical Pharmacology
PF-07202954 is a potent and selective inhibitor of hDGAT2. By in vitro biochemical 
assessment of hDGAT2, PF-07202954 inhibits hDGAT2 with an IC50 of 10.1 nM. The 
selectivity of PF-07202954 for DGAT2 was supported by in vitro studies demonstrating 
>4500-fold selectivity by biochemical assessment versus related acyltransferases including 
recombinant hDGAT1, hMGAT2, and hMGAT3, as well as mouse MGAT1. In primary 
cultures of human hepatocytes, PF-07202954 exhibits an IC50 of 11.4 nM for inhibition of 
hDGAT2. PF-07202954 also inhibits DGAT2 within rat and nonhuman primate primary 
hepatocytes, yielding IC50 of 114 nM and 35.4 nM, respectively.
In vivo, following single dose administration, PF-07202954 demonstrates robust, 
dose- dependent reduction of plasma and hepatic triacylglycerol in rats fed a sucrose diet. In
longer term studies in Western diet fed rats, PF-07202954 also reduces both plasma 
triacylglycerol and hepatic lipid accumulation. In line with the proposed mechanism of 
action, PF-07202954 dosing in both sucrose and Western diet fed rats results in suppression 
of key genes involved in hepatic lipid metabolism, including mRNA expression of Pcsk9. In 
these nonclinical models dosed with PF-07202954, Pcsk9 mRNA was decreased relative to 
vehicle treated animals by 64% and 75% in the Western and sucrose diet models, 
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2.2.2. Nonclinical PK and Metabolism
Single-dose PK studies with PF-07202954 were conducted after IV administration in rats, 
dogs, and monkeys and oral administration in rats and monkeys. PF-07202954 demonstrates 
incomplete oral absorption with mean F of 4% in rats and 21% in monkeys. PF-07202954 
exhibited moderate to high CLplasma and moderate Vss in rats, dogs, and monkeys, resulting in
a short terminal elimination t½ of ≤1.5 hours. Systemic exposure of PF-07202954 as 
measured by Cmax and AUC24 in repeat oral dose toxicity studies increased with increasing 
dose in rats and monkeys with evidence of some accumulation in both species. Systemic 
exposure of PF-07202954 was higher in female rats than in male rats, where sex-related 
differences were not observed in monkeys. In vitro, PF-07202954 showed moderate passive 
permeability and preliminary studies indicated that PF-07202954 was a substrate for MDR1
(also known as P-gp) and BCRP efflux transporters.
Following IV administration of PF-07202954, the percent of PF-07202954 dose recovered 
unchanged in urine was 12% (rat), 25% (dogs), and 2.0% (monkeys). The renal clearance 
estimates exceed GFR by ~2-fold indicating a net active renal elimination process in rats and 
dogs but not in monkeys. PF-07202954 is a substrate for the human OAT3 but not OCT1 or 
OCT2. PF-07202954 was moderately bound to plasma proteins with fu of PF-07202954 in 
plasma being 0.422 (rat), 0.531 (dog), 0.370 (monkey), and 0.382 (human). The
blood-to-plasma ratios of PF-07202954 in rat, dog, monkey, and human suggest that 
PF-07202954 does not preferentially distribute into plasma versus red blood cells.
In vitro metabolite profiling in mouse, rat, rabbit, monkey, and human matrices and rat and 
monkey plasma, suggests that the primary metabolic clearance mechanism for PF-07202954 
was oxidation with no unique human metabolites observed. Reaction phenotyping in human 
hepatocytes indicated CYP3A (>87%) was primarily responsible for the oxidative 
metabolism of PF-07202954 with minor contributions from CYP2C9 and CYP2C19. 
However, in humans, metabolic CL of PF-07202954 is projected to account for 
approximately 40% of total CL, with the remaining 60% as renal CL. Modeling suggests a 
low risk of clinical DDI with PF-07202954 as a victim upon coadministration with CYP3A4 
inhibitors or inducers. As OAT3 is predicted to contribute to the active renal secretion of 
PF-07202954 in humans, a potential risk of clinical DDI with PF-07202954 as a victim is 
anticipated upon coadministration with potent inhibitors of OAT3. At the projected effective 
human dose of 80 mg once daily, PF-07202954 has a low risk of eliciting DDI as a result of 
inhibition or induction of CYP enzymes or efflux and uptake transporters with the exception 
of direct inhibition of MATE1 and intestinal BCRP.
2.2.3. Biopharmaceutics
PF-07202954 is a weak base with pKa values of 7.5 and 2.5, thus exhibiting a strong 
pH-dependent change in solubility. It has high thermodynamic aqueous solubility at 
physiological pH. The solubility of PF-07202954 in simulated gastric fluid (pH 2.7) and 
unbuffered water (pH 8) is >27 mg/mL and 0.13 mg/mL, respectively. Solubility in 
simulated fasted and fed state intestinal fluids (pH 6.9 under both conditions) was observed 
to be 0.7 mg/mL and 1.2 mg/mL, respectively. Solubility of PF-07202954 is high relative to 


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the predicted clinical FIH dose range, thus the risk for solubility/dissolution-limited 
absorption and exposure-limiting precipitation is perceived to be low. Food is expected to 
have minimal impact on PF-07202954 PK – refer to Section 4.2.5. Preliminary in vitro 
studies suggest PF-07202954 exhibits moderate in vitro permeability and is a substrate for 
the intestinal efflux transporters (P-gp and BCRP) that could potentially lead to non-linear 
plasma PK and high variability in exposure at lower doses.
2.2.4. Nonclinical Safety
PF-07202954 was evaluated in safety pharmacology studies, genetic toxicology studies, and 
repeat dose toxicity studies, of up to 6 weeks in duration, in rats and cynomolgus monkeys.
Target organs in safety pharmacology and general toxicity studies included the CNS 
(convulsion), kidney/urinary system (degenerative/inflammatory process with evidence of 
altered renal function), and the CV system (increased QT and QTc-interval). Other key 
findings included nonadverse hematology changes and nonadverse findings in the 
gastrointestinal system. The highest NOEL for convulsion was 300 mg/kg which 
corresponded to total Cmax of 39,000 ng/mL. The NOEL for QTc-interval changes was 
30 mg/kg and corresponded to total Cmax of 2770 ng/mL. The NOAEL in the 6-week pivotal 
toxicity studies were 300 mg/kg/day (in rats) and 100 mg/kg/day (in monkeys). In rats, the 
NOAEL corresponded to a total Cmax of 6570 (in males) and 14,400 (in females) ng/mL and 
total AUC24 of 36,800 (males) and 89,100 (females) ng•h/mL. In monkeys, the NOAEL 
corresponded to a total Cmax of 14,500 ng/mL and total AUC24 of 88,500 ng•h/mL.
PF-07202954 was not genotoxic. PF-07202954 may have potential risk for phototoxicity 
based on its UV absorption profile and will be evaluated for phototoxicity during exploratory 
development prior to enrollment in Phase 3 clinical studies. Further details of the nonclinical 
safety program are provided in the current IB.
2.3. Benefit/Risk Assessment
This study is the first time that PF-07202954 will be administered to humans. For healthy 
participants participating in this 3-part study, no clinical benefit is expected. The purpose of 
the study is to provide the basis for further clinical development of PF-07202954 as a 
potential new pharmacological agent for the treatment of participants with NASH with liver 
fibrosis. As of the issuance of this protocol, no specific human risks have been identified; 
potential risks based on nonclinical studies are summarized in Table 1. The clinical impact of 
these potential risks will be minimized through the proposed cautious dose-escalation process 
wherein higher doses of both single- and repeated-oral doses of PF-07202954 will be 
administered only after lower doses have been found to be safe and well tolerated in this 
study and the a priori identified PK stopping limits will not be exceeded (refer to 
Section 6.6.1). In addition, this study includes standard, intensive inpatient monitoring of the 
participants following administration of single- and repeated-, escalating, oral doses of the 
study intervention.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-07202954 may be found in the IB, which is the SRSD for this 
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2.3.1. Risk Assessment
Table 1.
Potential Risks with PF-07202954 and C4171001 Design
Potential Risk of 
Clinical Significance
Summary of Data/ Rationale for Risk
Mitigation Strategy
Study Intervention – PF-07202954 
Decrease in renal 
function 
• In a 6 week toxicity study in rats, renal tubular 
degenerative/inflammatory process with a pattern 
consistent with obstructive nephropathy -
associated with evidence of altered renal function 
and lower urinary tract alterations without 
accompanying changes in SCr and BUN observed 
at the highest dose tested (1000 mg/kg/day) with 
most conservative total AUC24 (in male rats) of 
210000 ng•h/mL.
• Risk communicated through the IB;
• Heightened surveillance for potential case of acute kidney injury 
outlined in Section 7.1.2;
• PK stopping total AUC24 criterion set at ≥200-fold lower exposures –
refer to Section 6.6.1;
• Design features added including –
• Enrollment limited to those with normal renal function as defined 
by eGFR cut-offs using CKD-EPI formulae, and normal UACR and 
UPCR – refer to exclusion criterion #7 in Section 5.2;
• Conduct of UACR, UPCR at all timepoints that urinalysis is 
undertaken following single and repeated dosing
• Conduct of urine microscopy at all timepoints that urinalysis is 
undertaken following repeated dosing (in Part 2);
•
 
 
 
Delayed cardiac 
repolarization 
Increase QT and QTc observed in GLP CV study in 
monkeys at 14400 ng/mL (total Cmax).
• Risk communicated through the IB;
• Serial assessment of triplicate, 12-lead ECGs following single- and 
repeated- doses of study intervention (Section 8.2.3) along with 
continuous telemetry following single doses (Section 8.2.3.1);
• PK stopping total Cmax criterion set at close to 10-fold lower
(1450 ng/mL) – refer to Section 6.6.1.
Convulsions 
Convulsions noted in 1 monkey dosed 
500 mg/kg/day where total Cmax was 46000 ng/mL.
• Risk communicated through the IB;
• PK stopping total Cmax criterion set at the conservative 1/10th exposure 
at NOAEL in 6 week GLP monkey study (1450 ng/mL) – refer to 
Section 6.6.1;
• As designed, participants will be under closely monitored environment 
for ≥72 hours post (last) dose.
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Table 1.
Potential Risks with PF-07202954 and C4171001 Design
Potential Risk of 
Clinical Significance
Summary of Data/ Rationale for Risk
Mitigation Strategy
Skin sensitivity to light; 
sunburn
Based on UV absorption profiles, PF-07202954 
carries risk for phototoxicity.
Standard precaution as it relates to exposure to sunlight/high intensity 
UV light exposure including eye protection is proposed – refer to 
Section 5.3.3.
Exposure in utero
To date, EFD studies with PF-07202954 have not
been conducted:
• And PF-07202954 is not mutagenic, clastogenic 
or aneugenic in in vitro studies plus was negative 
in an in vivo rat micronucleus study.
• Risk communicated through the IB;
• Enrollment of WOCBP restricted to those using effective 
contraception – refer to Section 5.3.4 and Section 10.4:
• As a measure of caution, serum pregnancy testing undertaken in all
females.
• In males who are sexually active with a female partner of childbearing 
potential, use of barrier methods required/mandated – refer to 
Section 5.3.4 and Section 10.4.
DDIs resulting in 
change in exposure of 
background/concomitant 
medications
In vitro data indicate PF-07202954, at high doses, 
may be a CYP3A inducer.
• Enrollment of WOCBP restricted to those using effective 
contraception (with restrictions on use of some hormonal methods)
– refer to Section 5.3.4 and Section 10.4;
•
In vitro data indicate PF-07202954 is an inhibitor of 
MATE1, a renal transporter involved in tubular 
secretion of organic cations.
 
 
Study Procedures
In Part 1 and Part 2, 
number of serial and
parallel procedures 
carry risks for 
non-evaluable data
• Planned safety and PK evaluation is standard for 
FIH studies in healthy participants;
• But addition of parallel, multiple, clinical activity 
parameters done to enable more robust 
exposure:response characterization.
• At selected timepoints where evaluation of safety, PK, and clinical 
activity is planned in parallel, doability of all procedures is 
precedented at sites selected for this study;
 
 
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Table 1.
Potential Risks with PF-07202954 and C4171001 Design
Potential Risk of 
Clinical Significance
Summary of Data/ Rationale for Risk
Mitigation Strategy
In Part 2, conduct of 
different imaging 
assessments of liver fat 
during study 
(ie, quantitative 
ultrasound-based 
FibroScan®
 
 
Procedures are relatively safe; potential risk for 
non-evaluable images include: 
• Too much motion, for example, due to increased 
anxiety, claustrophobia;
• Ferric implants/devices, paramagnetic objects 
within/on body, ferric-containing tattoos in area of 
interest (abdomen, chest, arms);
• Minimum duration of a priori fast not followed. 
• Permitting pre-procedure use of short-acting anxiolytics to manage 
anxiety 
• Excluding participants if they have contraindications for MRI, or 
quantitative ultrasound-based assessments (FibroScan®);
• Clear communication via ICD of preparation for each visit including
duration of fast before procedures/visits.
In Part 1 and Part 2, 
dosing of study 
intervention with 
standard meal changes 
PF-07202954 exposure 
In vitro data indicate that PF-07202954 has 
moderate passive permeability (RRCK=2.9 x 10-6
cm/sec), higher solubility at lower pH – refer to 
Section 2.2.3.
• In Part 1 and Part 2, dosing with a standard (not high-fat/high-caloric) 
meal is proposed to permit assessment of clinical activity –
 
– refer to Section 4.2.5;
• Dose range evaluated is envisioned to be adjusted based on observed 
plasma PK while following dose-escalation principles – refer to 
Section 6.6.1.
Other Factors Potentially Impacting Study Results 
In Part 2, baseline liver 
fat 
 too 
low hence potentially 
not permitting 
assessment of primary 
pharmacology (ie, liver 
fat reduction)
Population eligible is healthy with evidence of 
simple hepatic steatosis assessed using quantitative 
ultrasound at Screen.
In Part 2, study requires double-confirmation of assessment of liver fat 
(via CAPTM using FibroScan®) and lack of overt liver 
inflammation/fibrosis (via VCTETM using FibroScan®) with eligibility 
required to be met prior to Baseline 
;
• CAPTM ≥270 dB/m when assessed on 2 different days permits 
>90% probability of liver fat being ≥6% liver fat on baseline 
;
• VCTE <7.0 kPa when assessed on 2 different days being highly 
suggestive of lack of clinically significant inflammation/fibrosis.10
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2.3.2. Benefit Assessment
The participants in this study are not expected to obtain any specific benefit beyond 
contributing to the process of developing new therapies in an area of unmet need. They will 
receive close monitoring of their safety via study procedures undertaken (eg, PE, 12-lead 
ECGs, vital signs) which will occur as outlined in this protocol.
In Part 1, all participants will receive single, oral, escalating doses of PF-07202954 and
placebo. Those enrolled in Part 2 will be randomized to placebo (1 in every 5 participants) 
or repeated, oral, escalating doses of PF-07202954 (4 in every 5 participants). In Part 3, if 
conducted, all participants will receive a single, oral dose of PF-07202954 following an 
overnight fast and with a high-fat/high-caloric morning meal.
2.3.3. Overall Benefit/Risk Conclusion
In consideration of the available nonclinical data and the measures taken to minimize risk to 
participants in this study, the overall benefit:risk profile for PF-07202954 supports initial 
clinical development for NASH with liver fibrosis.
3. OBJECTIVES AND ENDPOINTS
Table 2 outlines the key objectives and endpoints for Part 1, Part 2, and Part 3 (if conducted) 
of this study.
Table 2.
Key Objectives and Endpoints in Study C4171001
Study 
Objectives
Endpoints 
Part 1
Primary 
To evaluate safety and tolerability 
of single, oral, escalating doses of 
PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants.
Following assessments over ≥10 days of each Period 
and up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG.
Secondary 
To characterize the plasma PK
profile of PF-07202954 following 
administration of single, oral, 
escalating doses.
PK parametersa derived from plasma PF-07202954 
concentrations: 
Cmax, Tmax, AUClast, AUCinf, t½, as data permit.
Part 2
Primary 
To evaluate safety and tolerability
of repeated, oral, escalating doses 
of PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants with simple 
hepatic steatosis.
Following assessments over the duration of dosing and
up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG.
Secondary
To characterize the plasma and 
urine PK profiles of PF-07202954 
following administration of 
repeated, oral, escalating doses.
PK parametersa derived from plasma PF-07202954 
concentrations: 
Single dose: Cmax, Tmax, AUCtau on Day 1.


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Table 2.
Key Objectives and Endpoints in Study C4171001
Study 
Objectives
Endpoints 
• Repeated dose: 
•
Days 7 and 14 – Cmax, Tmax, AUCtau, as data 
permit.
•
Day 14 – t½ as data permit.
PK parametersa derived from urine PF-07202954 
concentrations on Day 14: Aetau, Aetau%, CLr.
Part 3, if conducted
Primary 
To characterize the effect of a 
high-fat/high-caloric meal, 
compared to following an overnight 
fast, on plasma PK profile of 
PF-07202954 following 
administration of a single oral dose 
to healthy, adults.
PK parametersa derived from plasma PF-07202954 
concentration: 
• Cmax, Tmax, AUClast, and AUCinf, as data permit.
Secondary
To evaluate safety and tolerability 
of a single, oral, dose of 
PF-07202954 administered with a
high-fat/high-caloric meal compared 
to following an overnight fast.
Following assessments over ≥5 days of each Period and
up to Day 30 ±2 days post last dose of study 
intervention –
• AEs;
• Clinical laboratory tests;
• Vital signs (including BP and pulse rate);
• Cardiac conduction intervals via 12-lead ECG.
a.
For a complete definition of all PK parameters refer to Table 8 and Table 9.
NOTE: For all non-PK related endpoints, baseline is defined as the time-matched data obtained while on placebo 
[Part 1], 0H assessment on Day 1 or 0-12H or 0-24H assessment prior to 1st dose [Part 2], or 0H assessment on Day 1 in 
each Period [Part 3], unless otherwise specified in the SAP.
4. STUDY DESIGN
4.1. Overall Design
The study is planned as a 3-part design with investigator- and participant-blinded
(sponsor-open), placebo-controlled, randomized, dose-escalation in Part 1 and Part 2; and a 
randomized, open-label design, in Part 3 (if conducted). Participants will receive oral dose(s) 
of PF-07202954 and/or placebo in this study. A total of up to 88 unique participants (16 in 
Part 1, up to 30-40 initially in Part 2 [and potential expansion to 50-60 post formal IA and 
protocol amendment], and a maximum of 12 in Part 3) are planned to be randomized in this 
study.
In Part 1, for individual participants, the total duration of participation from the Screening 
visit to the telephone Follow-up visit will be 9 weeks (minimum) to 14 weeks 
(maximum) - as summarized in Figure 1.
In Part 2, the total duration of participation in the study, for each participant, will be 
8 weeks (minimum) to 12 weeks (maximum), including the interval from the 1st Screening 
visit to the telephone Follow-up visit – refer to Figure 2.
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In Part 3, if conducted, the total duration of participation for each participant, from the 
Screening to the telephone Follow-up visit, will be 5 weeks (minimum) to 10 weeks 
(maximum) – as outlined in Figure 3.
4.2. Scientific Rationale for Study Design
4.2.1. Study Population
As is typical in the case for FIH studies, the population planned for this study will be
healthy, adult males and females. However, studies to evaluate the development toxicity of 
PF-07202954 have not been conducted and hence, the use of a highly effective method of 
contraception is required in males and females of childbearing potential (refer to 
Section 10.4).
In Part 1 and Part 3 (if conducted), the healthy population will be limited to the typical upper 
age limit (to 55 years) and BMI limits (to ≤30.5 kg/m2). However, in Part 2, allowance will 
be made to expand the age (to 65 years) and BMI limits (to ≤35.4 kg/m2) to enable ability to 
screen participants with simple hepatic steatosis, a benign condition notable for accumulation 
of liver fat of ≥5%, and thereby assess the effect of PF-07202954 on liver fat 
 
following 14 days of inpatient dosing. Ability to detect reductions in liver fat 
 with this duration of dosing with orally administered other 
DGAT2i is precedented.11,12 In addition, the population dosed in Part 2 will be confirmed as 
meeting all of the following criteria via double-confirmation between Screen and
Day -2 visits: 
•
Liver fat as assessed via quantitative ultrasound parameter CAPTM of ≥270 dB/m,
assessed using FibroScan®
•
Liver stiffness as assessed via quantitative ultrasound parameter VCTETM of 
<7.0 kPa, assessed using FibroScan® (suggestive of lack of inflammation/fibrosis as a 
result of abnormally accumulated liver fat);10
•
ALT and AST ≤1.5 x ULN.
While this study includes 3 Parts, a given participant can only be randomized and dosed in 
1 of the 3 parts; participants are not permitted to be randomized and dosed in multiple parts 
of this study. This restriction is placed to permit clinical experience with PF-07202954 to be 
garnered in unique participants.
4.2.2. Rationale for Part 1
Given the current study is the first time PF-07202954 will be administered to humans, an 
escalating single oral dose design is planned with careful assessment and ongoing review of 
safety data and PK of PF-07202954. Part 1 is designed as a randomized, dose -escalating,
cross-over, interleaving, placebo-controlled, 2-cohort, study with dosing of study 
intervention (PF-07202954/placebo) planned following ≥10 hours overnight fast, at 
approximately 8:00AM (±2 hours) to occur with standard morning meal provided ~30 mins 
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prior to dosing at 0H. By design, at each dose level, 6 participants are planned to receive 
PF-07202954 and 2 participants are planned to receive placebo with all participants at the 
end of Part 1 having received 1 dose of placebo and up to 3 unique doses of PF-07202954.
The rationale for selection of the starting (ie, first) dose level in Part 1 is outlined in 
Section 4.3.3. In addition, the highest anticipated steady-state AUC24 and Cmax for 
PF-07202954 in Part 1 will not exceed the pre-identified stopping exposure limit determined 
based on nonclinical toxicity study (refer to Section 6.6.1) nor exceed the highest feasible 
total daily dose of 2000 mg.
The design of Part 1 permits both a within and between participant assessment of 
safety/tolerability and dose-response for PK and exploration of effect on plasma PCSK9.
Furthermore, to permit an unbiased assessment of safety, the administration of active versus 
placebo in each Period will be double-blinded to both site staff (except those involved in 
preparation of doses) as well as the participants. However, to permit real-time review of the 
safety and PK data, the sponsor will be unblinded, although measures to limit degree of 
unblinding will be exercised – refer to Section 9.5 for details. In light of the findings in the 
6 week toxicity studies in rats and monkeys, the safety assessments envisioned in this study 
administrating investigational product for the first time to humans are outlined in Section 8.2.
For a given participant, dosing will be separated by ≥10 days, with this planned dosing 
interval deemed sufficient based on the predicted PF-07202954 effective half-life of 
approximately 8 hours. In addition, this interval accounts for the required time for review of 
the safety, tolerability, and PK data from each dosing period before making a decision on the 
subsequent PF-07202954 dose to be evaluated. The planned doses in the escalation sequence 
(refer to Table 3) may be modified or repeated, as guided by emerging safety and PK data but 
will follow the dose-escalation rules defined in Section 6.6.1. The data from participants as 
they receive placebo will be pooled and compared to data from each active dose to determine 
the next escalating dose of PF-07202954. The assessment of the full range of doses will 
require the planned 8 Periods of dosing (4 Periods per participant). In the event that 
additional dose-escalation is no longer warranted (eg, maximum tolerated dose identified, 
clear evidence of plateau in plasma PK based on observed data with at least 2 dose-levels), 
the additional periods in this 4-Period, cross-over design may be used to repeat a previously 
administered dose, study a lower and/or intermediate dose, and/or undertake an exploratory 
assessment of plasma PK with dosing following an overnight fast of ≥10 hours or dosing 
following a high fat/high caloric morning meal (compared to dosing following a standard 
morning meal in previous Periods within the same cohort) to explore any potential food 
effect. And pending observed plasma PK data from Part 1, this study may also conduct Part 3 
– refer to Section 4.2.4 – to compare plasma PK following dosing in the fasted state 
(Reference) to dosing with a high-fat/high-caloric morning meal (Test).


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4.2.3. Rationale for Part 2
The initiation of Part 1 and Part 2 of this study will be staged. The first dose level in Part 2 
will only initiate after at least 3 dose-levels, in Part 1, have been administered and safety plus 
PK data reviewed – refer to Section 4.3.4 for additional details regarding determination of the 
initial dose in Part 2 relative to dose(s) evaluated in Part 1. In addition, the highest 
anticipated steady-state AUC24 and Cmax for PF-07202954 in Part 2 will not exceed the 
highest single oral dose exposure observed to have an acceptable safety profile in Part 1 of 
this study nor exceed the highest feasible total daily dose of 2000 mg.
Part 2 of this study is designed to assess the safety, tolerability, and PK, as well as potentially 
assess/explore markers of clinical activity of escalating doses of PF-07202954 administered 
once daily for 14 days. In each cohort/dose level, 8 of the 10 participants randomized will 
receive PF-07202954 and 2 will receive placebo. At the end of the study, the intent will be to 
pool the participants who received placebo across the cohorts in Part 2 into 1 group.
The proposed duration of dosing (14 days) is deemed to be sufficient to assess steady-state 
safety, tolerability, PK, as well as explore effect on PF-07202954 on markers of clinical 
activity, given the projected plasma half-life of approximately 8 hours and afforded by the 
completed, GLP, 6 week, toxicity studies in rats and monkeys. The planned doses in the 
escalation sequence (refer to Table 4) may be modified or repeated, as guided by emerging 
safety, tolerability, and PK data (as well as data assessing clinical activity, when available).
In all cases, doses selected will follow the dose-escalation rules defined in Section 6.6.1.
To permit an unbiased assessment of safety, the administration of active versus placebo will 
be double-blinded to site staff (except those involved in preparation of doses) and the 
participants. However, to permit real-time review of the safety and PK data (as well as data
assessing clinical activity), the sponsor will be unblinded, although measures to limit degree 
of unblinding will be exercised –– refer to Section 9.5 for details. In light of the findings in 
the 6 week toxicity studies in rats and monkeys, the safety assessments are envisioned to be 
the standard used by the sponsor in trials administrating investigational product for the first 
time to humans as outlined in Section 8.2.
Based on nonclinical data, the potential exists that PF-07202954 causes induction of 
CYP3A4 mRNA.
 
In vitro data indicate that PF-07202954 is an inhibitor of the renal transporter MATE1 at 
clinically relevant concentrations. MATE transporters are involved in tubular secretion of 
organic cations in the kidney.13
 
 
 
Creatinine is actively secreted by 
OCT2/MATE in the kidney. In the setting of OCT2/MATE inhibition, SCr levels have been 
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reported to increase slightly.13 In order to assess the possibility of OCT2/MATE 
inhibition-related increases in SCr, SCysC will be collected in the standard safety labs, in 
addition to creatinine, in order to evaluate eGFR15 – refer to Section 7.1.2 for additional 
details.
4.2.3.1. Assessment of Clinical Activity in Part 2
 
 
 
The effect of PF-07202954 on the primary pharmacology 
 
will be measured and potential dose-response characterized for this effect 
 
 – refer to Section 9.4.4.1. Using this design, the 
cumulative number of participants dosed with placebo (n=8) along with the 8 participants at 
each dose of PF-07202954 would allow for potential characterization of the dose response 
for the effect of PF-07202954 
.
4.2.4. Rationale for Part 3
Conduct of Part 3 in this study is conditional on whether exploration of plasma PK using 
fasted (and/or high-fat/high-caloric meal) was undertaken in Period 4 in 1 or both cohorts in 
Part 1 or if the results of the exploratory food effect in Part 1 is inconclusive (eg, due to large 
variability in plasma PK).
Pending observed data in Part 1 (including potential assessment of plasma PK with dosing 
following an overnight fast of ≥10 hours – refer to Section 4.2.2) and Part 2, where dosing 
will occur with a standard morning meal, assessment of the effect of a high-fat/high-caloric 
meal versus a fasted state on the PK of PF-07202954 may be conducted in Part 3. If Part 3 is 
conducted, it will occur only after completion of Part 1, though it may occur in parallel to 
Part 2. Part 3 will be conducted at the discretion of the sponsor.
This part will be a single cohort, randomized, open-label, 2-period, crossover design, 
randomizing 8 (minimum) to 12 (maximum) participants who will receive PF-07202954 
once with a high-fat/high-caloric meal and once following an overnight fast of ≥10 hours 
with the order randomly assigned. Since the dose in this part (refer to Section 4.3.5) will be 
selected based on observed safety, tolerability, and PK of single doses in Part 1 and the dose 
selected will be lower than the highest dose tested in Part 1, standard safety monitoring will 
be used in this part of the study.
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4.2.5. Rationale for Dosing with Standard Meal in Part 1 and Part 2
In Part 1 and Part 2 of this study, PF-07202954 will be administered with a standard morning 
meal because PF-07202954 is expected to be administered with food in clinical practice and 
administration with a meal helps in the assessment of the effect of PF-07202954 
 
Although food is expected to have 
minimal impact on PF-07202954 exposures at doses ≤1500 mg based on the physical and 
chemical properties of PF-07202954 and simulations of a PBPK model, the effect of a 
high-fat/high-caloric meal on plasma concentrations of PF-07202954 may be evaluated in 
Part 1 and/or Part 3 of this study.
 
 
 
 
  
4.2.7. Rationale for Banked Sample Collection 
Banked Biospecimens will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention – refer to Section 8.7.2.
4.3. Justification for Dose
The proposed doses of PF-07202954 in Part 1 (single, escalating doses) and Part 2 (repeated,
escalating doses) were derived based on cumulative nonclinical data including in vitro and in 
vivo pharmacology and PK data and the 6-week toxicity studies completed in rats and 
monkeys. The PF-07202954 doses in Part 1 and Part 2 beyond the starting dose in Part 1 may 
be modified based on emerging human safety, tolerability, and PK data in the current study.
4.3.1. Projected Human PK Parameters and Effective Human Dose
In humans, PF-07202954 is predicted to have a CLplasma of 3.34 mL/min/kg (hepatic 
clearance of 1.34 mL/min/kg; renal clearance of 2.0 mL/min/kg), F of 32% (oral absorption 
of 35%), Vss of 2.30 L/kg, and an effective t½ of approximately 8 hours. 
The average total Ceff for PF-07202954 over the once daily dosing interval of 76.6 ng/mL
(66.8 nM unbound), is equivalent to approximately IC85 of the in vitro human biochemical 
and human hepatocyte potencies. This exposure is projected with a clinical dose of 80 mg 
administered once daily of PF-07202954 and predicted to lower hepatic steatosis by 
≥35% following 14 days of dosing (ie, similar magnitude as observed following 14 days of 
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dosing of 2 other oral DGAT2i).11,12 At the PF-07202954 dose of 80 mg administered once 
daily, projected exposures are total Cmax of 106 ng/mL and total AUC24 of 1840 ng•h/mL.
4.3.2. Human Exposure Limits
Guided by the target organs of toxicity identified in the completed GLP, 6 week studies in 
rats and monkeys (refer to Section 2.2.4, Table 3 and Table 4), the PK exposure limits in this 
study are proposed as –

In Part 1 and Part 2: Total Cmax: 1450 ng/mL – reflecting the conservative 1/10th
of the exposure at the NOAEL dose (100 mg/kg/day) in the 6 week toxicity study in 
monkeys [for the convulsions observed in 1 monkey in the exploratory toxicity study 
following PF-07202954 dose of 500 mg/kg/day];

In Part 1: Total AUC24: 18,400 ng•h/mL – reflecting 50% of exposure in males at
the NOAEL dose (300 mg/kg/day) in the 6-week toxicity study in rats [for adverse 
renal findings];

In Part 2: Total AUC24: 3,680 ng•h/mL – reflecting 10% of exposure in males at
the NOAEL dose (300 mg/kg/day) in the 6-week toxicity study in rats [for adverse 
renal findings] with revision to this stopping limit to be considered, via a protocol 
amendment post formal interim analysis, based on observed data in Part 1 and Part 2 
in this study.
4.3.3. Rationale for Dose Selection in Part 1
The objective of Part 1 of this study is to explore the safety, tolerability, and plasma PK of 
PF-07202954 after administration of single escalating oral doses across a wide exposure 
range and potentially up to the maximum predefined human exposure limits (Table 3). 
Dosing will occur with a standard morning meal. The doses presented are projected based on 
nonclinical data and may be modified based on emerging human safety, tolerability, and PK 
data. Human PK parameter estimates, toxicokinetic data, and projected effective
concentrations were used to establish the initial range of planned doses in this study. The 
projected human exposures are based on assuming dose-proportional increases in exposure 
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Table 3.
Predicted Human Exposures at Proposed Single Doses of PF-07202954
Dose 
(mg)
Total Concentrations
Safety Marginsb,c
Cmaxa (ng/mL)
AUC24a (ng•h/mL)
Cmaxb
AUC24c
10
10
180
140
102
30
31
540
46
34
100
100
1800
14
10
300
310
5400
4.6
3.4
600
620
11,000
2.3
1.7
1000d
1040
18,000
1.4
1.0d
a.
Cmax and AUC24 were estimated using projected human PK parameters for PF-07202954 using
CLplasma=3.34 mL/min/kg; Vss=2.3 L/kg; F=0.32; ka=0.2 h-1; human fu=0.382; body weight=70 kg.
b.
Cmax safety margins at the proposed doses were calculated based on total exposure at 1/10th of the exposure at the 
NOAEL dose in the 6 week toxicity study in monkeys [for the convulsions in 1 monkey in the exploratory toxicity 
study following PF-07202954 dose of 500 mg/kg/day]; human PF-07202954 Cmax exposures will be limited to 
total Cmax=1450 ng/mL.
c.
AUC24 safety margins at the proposed doses were calculated based on 50% of total exposure at the NOAEL dose in 
the 6-week toxicity study in rats [for adverse renal findings]; human PF-07202954 AUC24 exposures will be limited 
to total AUC24=18,400 ng•h/mL.
d.
Highest feasible total daily dose is 2000 mg; dose-increments as well as maximum dose may be adjusted up or down 
as guided by observed safety/tolerability, and plasma PK but projected PK will not exceed PK stopping limits.
The starting dose of PF-07202954 was informed by the on-target effect of DGAT2i –
namely, in vitro human DGAT2 biochemical and hepatocyte assays as well as results from 
the evaluation of 2 oral DGAT2i11,12 for effect on hepatic steatosis following 14 days of 
dosing. The 10 mg starting dose of PF-07202954 was selected as it is projected to achieve 
approximately IC50 for DGAT2 inhibition at Cmax with this exposure, when adjusted for 
potency differences which were found to be well tolerated with 2 other DGAT2i.11,12
Furthermore, adverse effects due to off-target effects are not expected at this low starting 
dose based on completed toxicity studies with PF-07202954 in rats and monkeys.
The dose range to be studied was selected to bracket the expected clinically effective dose 
range in humans for clinically relevant pharmacological activity of hepatic steatosis and 
providing safety coverage for a wide range of PF-07202954 doses.
The dose/exposure- escalation increments are planned to be up to approximately 
semi-logarithmic increases in exposure from the previous highest dose. The actual doses, 
target exposures, and/or dose increments may be adjusted (higher or lower) during the study 
based on emerging human safety, tolerability, and PK data, but projected exposures will not
exceed the predefined human exposure limits and the dose-escalation, and stopping rules 
outlined in Section 6.6.1.
4.3.4. Rationale for Dose Selection in Part 2
The objective of Part 2 of this study is to assess the safety, tolerability, and PK along with 
explore effect on markers of clinical activity with administration of repeated, escalating 
doses of PF-07202954 across a wide exposure range. The dosing frequency will be once
daily for 14 days with dosing occurring with a standard morning meal.


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In Part 2, the selection of the starting dose will be: (1) at least ≤ semi-logarithmic lower than 
a dose previously administered in Part 1 and observed to have an acceptable safety profile; 
(2) projected to have total daily steady-state exposures (Cmax, Cmin, and AUC24) that have 
been observed to be well-tolerated following single dose administration in Part 1; and 
(3) accounting for the accumulating safety and tolerability data from the escalating doses in 
Part 1 with the understanding that dosing in Part 2 may be paused or stopped based on 
emerging safety signals. 
The proposed starting dose level, in Part 2, is 10 mg once daily with this dose projected to 
elicit minimal clinical activity with anticipated Cmax more than 5-fold lower than Ceff. The 
proposed doses, along with anticipated margins over the PK stopping limits are summarized 
in Table 4.
Table 4.
Predicted Human Steady-State Exposures at Proposed Repeated Doses of 
PF-07202954
Dose 
(mg/day)
Total Concentrations
Safety Marginb,c
Cmaxa (ng/mL)
AUC24a (ng•h/mL)
Cmaxb
AUC24c
10
13
230
110
16
30
39
680
37
5.4
100
130
2300
11
1.6
160
210
3600
6.9
1.0
300d
390
6800
3.7
0.54d
600d
790
14,000
1.8
0.26 d
1000d
1300
23,000
1.1
0.16d
a.
Cmax and AUC24 were estimated using projected human PK parameters for PF-07202954 using
CLplasma=3.34 mL/min/kg; Vss=2.3 L/kg; F=0.32; ka=0.2 h-1; human fu=0.382; body weight=70 kg.
b.
Cmax safety margins at the proposed doses were calculated based on total exposure at 1/10th of the exposure at the 
NOAEL dose in the 6 week toxicity study in monkeys [for the convulsions in 1 monkey in the exploratory toxicity 
study following PF-07202954 dose of 500 mg/kg/day]; human PF-07202954 Cmax exposures will be limited to 
total Cmax=1450 ng/mL.
c.
AUC24 safety margins at the proposed doses were calculated based on 10% of total exposure at the NOAEL dose in 
the 6-week toxicity study in rats [for adverse renal findings]; human PF-07202954 AUC24 exposures will be limited 
to total AUC24=3,680 ng•h/mL – with revision to this stopping limit to be considered, via a protocol amendment 
post formal interim analysis, based on observed data in Part 1 and Part 2 in this study.
d.
Highest feasible total daily dose is 2000 mg; dose-increments as well as maximum dose may be adjusted up or down 
as guided by observed safety/tolerability, and plasma PK (as well as data reflecting clinical activity) but projected 
PK will not exceed PK stopping limits; furthermore, these higher dose(s) may be evaluated based on observed data 
in Part 1 and Part 2 in this study but only after a protocol amendment.
The starting dose may be refined to be as low as 5 mg, and as high as 20 mg, once daily, 
guided by observed safety/tolerability and plasma PK in Part 1. As planned, the starting dose 
in Part 2 will not exceed 20 mg once daily. Subsequent cohorts will receive escalating doses, 
at approximate semi-logarithmic increments in dose/exposure, as guided by observed 
safety/tolerability, and plasma PK with repeated dosing. In addition, emerging data 
reflecting markers of clinical activity 
 
 will be considered in determination of maximum repeated 
dose-level of PF-07202954 evaluated. In all cases, the projected exposure at the highest dose 
evaluated will not exceed the preidentified PK stopping limits.
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The range of doses proposed in Part 2 are also motivated by the objective to characterize the 
dose-response for effect of PF-07202954 in liver fat 
As such, 
across the proposed dose levels, it is envisioned that at least 1 dose will be at or below, plus 
additional doses above, the projected ED50 for effect on liver fat.
4.3.5. Rationale for Dose Selection in Part 3
As outlined in Section 4.2.4, conduct of Part 3 is conditional on results from Part 1. If 
Part 3 is conducted, a single dose level of PF-07202954 will be evaluated. Dose selection 
will be based on emerging safety, tolerability, and PK data from Part 1 and Part 2, in this 
study. The dose for Part 3 will be less than or equal to the highest dose tested in 
Part 1 observed to be well tolerated.
 
 
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases 
for a given Part (ie, 1, 2, or 3) of the study, including the last scheduled procedure shown in 
the SoA-Table A, SoA-Table B, and SoA-Table D.
The end of the study is defined as the date of the last visit of the last participant in the study, 
globally.
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. In Part 1 and Part 3, male and female participants must be 18 to 55 years of age,
inclusive, at the time of signing the ICD:
•
In Part 2, the upper limit of acceptable age will be extended to 65 years, 
inclusive, at the time of signing the ICD;
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
Refer to Section 10.4 for reproductive criteria for male (Section 10.4.1) and 
female (Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Male and female participants who are healthy as determined by medical evaluation 
including medical history, PE, laboratory tests; plus in Part 1 only, cardiac telemetry 
monitoring.
3. In Part 2, only, at Screen and Day -2, meet the following criteria based on 
assessment via FibroScan®, with a single repeat permitted, on a separate day, to 
assess eligibility, if needed, at each of these 2 visits:

CAP™ ≥270 dB/m;

VCTE™ <7.0 kPa.
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
5. BMI of ≥17.5 and ≤30.5 kg/m2 and a total body weight >50 kg (110 lb):

In Part 2, upper limit of acceptable BMI will be extended up to 35.4 kg/m2, 
inclusive;

In all 3 Parts, a single repeat assessment of body weight and/or BMI permitted on 
a different day to assess eligibility, if needed.
Informed Consent:
6. Capable of giving signed informed consent as described in Section 10.1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, CV, hepatic, psychiatric, neurological, or allergic disease 
(including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at 
the time of dosing).


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2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, 
HBcAb, or HCVAb; though hepatitis B vaccination (or HBsAb positive result) is 
allowed.
4. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
Prior/Concomitant Therapy:
5. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 -half-lives (whichever is longer) prior to the first dose of study 
intervention - refer to Section 6.5 for additional details.
Prior/Concurrent Clinical Study Experience:
6. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of study intervention
used in this study (whichever is longer).
Diagnostic Assessments:
7. Results as reported by the sponsor-identified laboratory(ies), at Screen in all 3 Parts 
(and Day -2, in Part 2) as below with a single repeat of any of these parameters
permitted to assess eligibility, if needed:

ALT >ULN (in Part 1 and Part 3) or >1.5x ULN (in Part 2, only);

AST >ULN (in Part 1 and Part 3) or >1.5x ULN (in Part 2, only);

ALP >2x ULN; 

TBili >ULN and direct bilirubin >ULN:

Note: Participants with a history of Gilbert syndrome would be eligible for
this study provided direct bilirubin level is ≤ULN, and hemoglobin and 
reticulocyte count are within the reference range of the sponsor-identified
laboratory(ies).

Fasting Plasma Glucose >125 mg/dL (6.9 mmol/L);


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•
Fasting serum TG >150 mg/dL (1.69 mmol/L) – in Part 1 and Part 2:
•
Part 3 does not include assessment of markers of clinical activity 
 
hence no associated exclusionary criteria proposed.
•
eGFR (using serum creatinine and CKD-EPI formulae) of ≤90 mL/min/1.73 m2 at 
time of signing ICD;
•
UACR >30 mg/g on spot urine collection;
•
UPCR >200 mg/g on spot urine collection.
8. A positive urine drug test for illicit drugs as reported by laboratory, at Screen in all 
3 Parts (and Day -2, in Part 2, only); this single laboratory assessment is not
permitted to be repeated to confirm eligibility.
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. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may
affect participant safety or interpretation of study results: 
•
Examples include - baseline QTcF interval >450 msec, 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 baseline uncorrected QT interval is >450 msec, this interval should be 
rate-corrected using the Fridericia method and the resulting QTcF should be used 
for decision making and reporting –
•
If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be 
repeated 2 more times and the average of the 3 QTcF or QRS values should be 
used to determine the participant’s eligibility;
•
Computer-interpreted ECGs should be overread by a physician/medical 
provider experienced in reading ECGs before excluding participants.
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Other Exclusions:
11. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening:

Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more 
alcoholic drinks in about 2 hours;

As a general rule, alcohol intake should not exceed 14 units per week (in males) 
and 7 units per week (in females) – where 1 unit = 8 oz. (240 mL) beer, 1 oz.
(30 mL) of 40% spirit, or 3 oz. (90 mL) of wine.
12. Use of tobacco- or nicotine- containing products in excess of the equivalent of 
5 cigarettes per day or 2 chews of tobacco per day.
13. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing.
14. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is used to flush IV catheters used during serial blood collections.
15. Unwilling or unable to comply with the lifestyle considerations outlined in 
Section 5.3.
16. In Part 2 only, participants meeting criteria for contraindication to undergoing 
imaging assessments including –

Active placement of medical devices in/on thoracic cavity as these interfere with 
use of ultrasound-based imaging modalities, and MRI;

History/evidence of any of the following: 

Contraindication to MRI such as ferric implant;

History of severe claustrophobia impacting ability to perform MRI during the 
study even despite mild sedation/treatment with a short-acting anxiolytic; 

Inability to lie still within the closed environment of the MRI scanner or
maintain a breath hold for the required period to acquire images even despite
mild sedation/treatment with an anxiolytic.
17. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members.


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Randomization Criteria – Parts 1, 2, and 3
Participants will be randomized into the study provided they have satisfied all the following 
criteria: 

Eligibility criteria outlined in Section 5.1 and Section 5.2;

In addition, prior to dosing on Day 1, the results of the clinical laboratory tests 
(including urine drug test) conducted upon each inpatient admission must be 
deemed to have no clinically significant findings, in the opinion of the PI, and as such 
permit (continued) participation in this study.
In Part 1, participants in the 2 cohorts will be randomized per the scheme summarized in 
Table 5 with the actual dose administered following the proposed dose-escalation approach 
outlined in Section 4.3.3 and Table 3.
Table 5.
Study C4171001 - Part 1 - Randomization Scheme
Cohort
Sequence
Perioda
1
2
3
4b
1
(n=8)
1 (n=2)
Placebo
Dose 3
Dose 5
Dose 7c
2 (n=2)
Dose 1
Placebo
Dose 5
Dose 7c
3 (n=2)
Dose 1
Dose 3
Placebo
Dose 7c
4 (n=2)
Dose 1
Dose 3
Dose 5
Placeboc
2
(n=8)
5 (n=2)
Placebo
Dose 4
Dose 6
Dose 8c
6 (n=2)
Dose 2
Placebo
Dose 6
Dose 8c
7 (n=2)
Dose 2
Dose 4
Placebo
Dose 8c
8 (n=2)
Dose 2
Dose 4
Dose 6
Placeboc
a. In each dose level/Period, the dose being evaluated will be known to the investigator(s) and participants; however, to 
preserve the double-blind design which participant is receiving PF-07202954 versus placebo will not be known by 
the investigator(s) and participants.
b. Pending observed safety/tolerability and plasma PK in previous Periods, an exploratory assessment of plasma PK 
with dosing following an overnight fast of ≥10 hours and/or dosing with high-fat/high-caloric meal (compared to 
dosing following a standard morning meal in previous Periods) may be considered.
c. Dose 7 and/or Dose 8 if used to assess plasma PK with dosing in fasted state and/or post high-fat/high-caloric meal –
pending observed safety, and PK in previous Periods – will limit the within-participant assessment of food effect to 4
participants on PF-07202954.
In Part 2, participants in each cohort will be randomized to PF-07202954 or placebo in a 
4:1 ratio with 10 participants dosed in each cohort.
In Part 3, if conducted, a total of 8 (minimum) to 12 (maximum) participants will be 
randomized to receive PF-07202954 in the 2 periods – once with a high-fat/high-caloric meal 
and once following an overnight fast of ≥10 hours – with the order randomly assigned. 
5.3. Lifestyle Considerations
After confirmation of eligibility at Screen, participants will be instructed to maintain the 
following guidelines starting prior to each inpatient admission and for the duration of their 
participation in the study. 


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5.3.1. Meals and Dietary Restrictions
While inpatient, the meals consumed are expected to follow the restrictions outlined below 
with participants encouraged to complete each meal.
•
Participants must abstain from all food and drink (except water) –
•
At least 4 hours prior to any non-lipid-related safety laboratory evaluations;
•
At least 10 hours prior to fasting clinical laboratory evaluations when fasting lipid 
panel is included.
•
Participants will refrain from consuming red wine, grapefruit, or grapefruit -related citrus 
fruits (eg, Seville oranges, pomelos, fruit juices) from 7 days prior to the first dose of 
study intervention until collection of the final PK blood sample.
•
Water may be consumed without restrictions both prior to and after study intervention 
administration when dosing occurs following a standard morning meal
(or high-fat/high-caloric meal).
•
Meals in Part 1 and Part 2:
•
All meals are standard meals unless Period 4 in 1 or both cohorts in Part 1 are used 
to explore effect of fasted state and/or high-fat/high-caloric meal on plasma PK.
•
On non-dosing days while inpatient, as appropriate, standard morning meal, lunch, 
and evening meal (along with an evening snack) are to be provided at a similar clock 
time to the clock time when these meals are offered on dosing days:
•
In Part 2, on days of 
 assessment, time of meal(s) may be adjusted to 
aide scheduling this assessment at the 
 facility while maintaining the 
minimum required pre-procedure fast of ≥4 hours.
•
The 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;
•
If participants cannot complete the meals, the portion consumed in 25% 
increments will be documented and potential impact on results assessed by the 
sponsor study team on a case-by-case basis.
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
On dosing days while inpatient:

Standard morning meal will be provided following on overnight fast of ≥10 hours
and at approximately 30 minutes prior to dosing at 0 H (or similar clock time on 
non-dosing days), consumed over approximately a 20-minute period
(ie, completed approximately 10 minutes prior to dosing);

Lunch will be provided approximately 5 hours after morning dosing, at 0H;

Evening meal will be provided approximately 12 hours after morning dosing, 
at 0H;

An evening snack may be permitted; however, the need to ensure an overnight 
fast of ≥10 hours is required to enable assessment of clinical laboratory tests the 
next morning.

In Part 1, Period 4 only, dosing may be altered (refer to Section 4.2.2) and can occur 
either following an overnight fast of ≥10 hours and/or with a high-fat/high-caloric 
meal; if this occurs, dosing will occur per the conditions outlined below for Part 3.

Meals in Part 3 (if conducted) will be standard or high-fat/high-caloric breakfast:

In both Periods while inpatient, as appropriate, standard breakfast (except Day 1), 
lunch, and evening meals (along with an evening snack) are to be provided at a 
similar clock time to when these meals are offered on dosing days;

The total daily nutritional composition should be approximately 55% carbohydrate, 
30% fat, and 15% protein – in both Periods;

Dosing in Fasted State: On Day 1, dosing will occur following an overnight fast of 
≥10 hours with water only, with the standard morning meal not offered:

When dosing is in the fasted state, water is permitted until 1 hour prior to dosing 
and water may be consumed without restriction beginning at 1 hour after dosing.

Dosing in Fed State: On Day 1, following an overnight fast of ≥10 hours, 
participants should start a high-fat/high-caloric breakfast approximately 30 minutes 
prior to PF-07202954 administration:

This breakfast will be consumed over approximately 20-minute interval and 
PF-07202954 administered within approximately 10 minutes after completion of 
the meal at 0H;


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
Breakfast will be a high-fat/high-caloric meal consistent with the FDA 
recommendation for a high-fat/high-caloric meal with a representative example 
being: 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter, 4 oz. 
of hash brown potatoes, and 8 oz. of whole milk.

Lunch will be provided approximately 5 hours after morning dosing at 0H;

Evening meal will be provided approximately 12 hours after morning dosing;

An evening snack may be permitted; however, the need to ensure an overnight fast of 
≥4 hours is required to enable assessment of clinical laboratory tests the next 
morning.
5.3.2. Caffeine, Alcohol, and Tobacco

Participants will abstain from caffeine-containing products for ≥24 hours prior to the 
start of dosing until collection of the final PK sample in each study period (in Part 1 and 
Part 3) or last PK collection prior to discharge from the CRU (in Part 2);

Participants will abstain from alcohol for ≥24 hours prior (or as specified above for red 
wine) to admission to the CRU and continue abstaining from alcohol until collection of 
the final PK sample of each study period. Participants may undergo an alcohol breath test 
or blood alcohol test at the discretion of the investigator;

Participants will abstain from the use of tobacco- or nicotine- containing products for 
≥24 hours prior to dosing and during confinement in the CRU.
5.3.3. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for ≥48 hours prior to each blood collection for clinical laboratory 
tests. Walking at a normal pace will be permitted;

In order to standardize the conditions on PK sampling days, participants will be required 
to refrain from lying down (except when required for BP, pulse rate, and ECG 
measurements), eating, and drinking beverages other than water during the first 4 hours 
after dosing;

In Part 1 only, participants will be confined to the procedure room for the first 4 hours
after dosing on Day 1 during continuous cardiac monitoring, except to use the bathroom.
After this, if the equipment setup allows, participants may be ambulatory during the ECG 
monitoring period, but should not engage in strenuous activities. If equipment does not 
allow ambulation, appropriate accommodations will be made by the investigator site to 
facilitate continuous monitoring (eg, bedside urinals should be provided to accommodate 
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
Participants will be advised to avoid direct sunlight exposure or any high intensity UV
light exposure, from the first day of dosing with study intervention and until the on-site 
Follow-up visit. In addition, participants will be instructed to wear eye protection and 
apply sun cream/lotion with a high sun protection factor, as appropriate.
5.3.4. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. At timepoints indicated in the schedule of activities (SoA-Table A, SoA-Table B, 
and SoA-Table D), the investigator or designee will inform the participant of the need to use 
highly effective contraception consistently and correctly and document the conversation and 
the participant’s affirmation in the participant’s chart (participants need to affirm their 
consistent and correct use of at least 1 of the selected methods of contraception). In addition, 
the investigator or designee will instruct the participant to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the participant
or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study. Screen 
failure data are collected and remain as source and are not reported to the clinical database.
Individuals who do not meet the criteria for participation in 1 of the 3 Parts of this study and
are screen failed may be rescreened for a different Part of this 3-Part study.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, the term investigational product (ie, IP) may be used 
synonymously with study intervention and refers to all of the following:

Placebo for PF-07202954;

PF-07202954.
6.1. Study Intervention(s) Administered
For all parts of this study, PF-07202954 and placebo will be provided by Pfizer as bulk 
powders for extemporaneous preparation of oral suspension at the CRU.


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PF-07202954 and placebo will be presented to the participants in individual dosing 
containers.
6.1.1. Administration

Part 1 and Part 2: following an overnight fast of ≥10 hours, participants will receive the 
study intervention with a standard morning meal at approximately 08:00 hours 
(±2 hours):

NOTE: if up to 2 of the 8 periods in Part 1 are being utilized to assess plasma PK in 
the fasted state and/or with high-fat/high-caloric meal, dosing will occur in the 
appropriate/respective setting (ie, overnight fast of ≥10 hours or with 
high-fat/high-caloric meal).

Part 3: following an overnight fast of ≥10 hours, participants will receive the study 
intervention either with water (fasted state) or with a high-fat/high-caloric meal at 
approximately 08:00 hours (±2 hours), in each of the 2 Periods, per randomization 
assignment.
In all cases, investigator site personnel will administer study intervention during each period 
with ambient temperature water to a total volume of approximately 240 mL;

Adequate measures to ensure taste masking will be performed prior to administration of 
the study intervention, if needed;

Additional water (up to 120 mL) may be consumed by the participants (eg, extra rinse) in 
an attempt to ensure that the full dose is consumed – with such instances documented in 
the source at the site;

Administration of study intervention will occur according to the EDR;

In order to standardize the conditions on PK sampling days, all participants will be 
required to refrain from lying down (except when required for BP, pulse rate, and ECG 
measurements), eating, and drinking beverages other than water during the first 4 hours 
after dosing.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
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 


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minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the PCRU local/site procedures.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. See the EDR for storage conditions of the study intervention once prepared.
7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the PCRU’s local/site procedures. All destruction must 
be adequately documented. If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with 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.


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For Parts 1, 2, and 3: PF-07202954 and placebo oral dosing suspensions will be prepared in 
the CRU by 2 operators, 1 of whom is a pharmacist. Details of dose preparation will be given 
in a separate EDR. Prepared doses will be provided in unit dose containers and labeled in 
accordance with Pfizer regulations and the investigator site’s labeling requirements.
For Parts 1 and 2: In order to maintain the blind, PF-07202954 and placebo will be prepared 
by qualified unblinded site personnel according to the EDR with study intervention
administered in a blinded fashion to the participant. 
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
The investigator will assign participant numbers to the participants as they are screened for 
the study. Pfizer will provide a randomization schedule to the investigator and, in accordance 
with the randomization numbers, the participant will receive the study treatment regimen 
assigned to the corresponding randomization number.
Participants will be randomly assigned to receive study intervention from a central 
randomization scheme. In Part 1 and Part 2, investigators will remain blinded to each 
participant’s assigned study intervention throughout the course of the study. In order to 
maintain this blind, an otherwise uninvolved third party (for example, a pharmacist) will be 
responsible for the preparation and dispensing of all study intervention according to the
randomization schedule and assigned treatment for the individual participant.
For Part 3, the investigator’s knowledge of the treatment should not influence the decision to 
enroll a particular participant or affect the order in which participants are enrolled.
6.3.2. Breaking the Blind – Part 1 and Part 2, only 
The method for breaking the blind will be manual. In case of an emergency, the investigator
has the sole responsibility for determining if unblinding of a participant’s treatment 
assignment is warranted. Participant safety must always be the first consideration in making 
such a determination. If the investigator decides that unblinding is warranted, the investigator
should make every effort to contact the sponsor prior to unblinding a participant’s treatment 
assignment unless this could delay further management of the participant. If a participant’s 
treatment assignment is unblinded, the sponsor must be notified within 24 hours after 
breaking the blind. When the blinding code is broken, the reason must be fully documented 
and entered on the DCT.
Blood specimens will be obtained from all participants for PK analysis to maintain the study 
blind at the investigator site. Only the investigator site staff and blinded study monitor, if 
assigned, will be blinded to study treatment. A limited number of the sponsors’ study team 
personnel will be unblinded to participant treatments in order to permit real-time 
interpretation of the safety and PK data; and provide information necessary to potentially 
alter the dose-escalation sequence. The blinded study monitor, if assigned, will remain 
blinded to treatment until all monitoring for the study has been completed. Specimens from 


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participants randomized to placebo will not be routinely analyzed. To minimize the potential 
for bias, treatment randomization information will be kept confidential by Pfizer unblinded 
personnel and will not be released to the blinded investigator or blinded investigator site 
personnel until the study database has been locked or the investigator requests unblinding for 
safety reasons.
6.4. Study Intervention Compliance
In Part 1, Part 2, and Part 3, 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 DCT. 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.
6.5. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention –

Limited use of nonprescription medications that are not believed to affect participant
safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor;

Acetaminophen/paracetamol may be used at doses of ≤1 gram per day;

Females using estrogen containing hormonal contraceptives or taking estrogen 
containing HRT may be eligible to participate in this study if they are willing to 
discontinue therapy ≥28 days prior to the first dose of study intervention and remain 
off hormonal therapy for the duration of the study:

Depo-Provera® must be discontinued at least 6 months prior to the first dose of 
study intervention.
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention
will be documented as concomitant treatments.


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6.6. Dose Modification
The dosing schedule may be adjusted to repeat 1 or more dose level(s) to further evaluate 
safety, tolerability, or plasma PK of PF-07202954, and/or explore markers of clinical activity 
at a given dose level or to add cohorts to evaluate additional dose levels – as described in 
Section 4.3. The study procedures for these additional participant(s)/cohort(s) will be the 
same as that described for other study participants/cohorts in this protocol.
6.6.1. Dose-Escalation and Stopping Rules
Dose-escalation stopping rules will be used to determine whether the maximal tolerated dose 
has been attained. Dose-escalation may be stopped if it is determined that the limits of safety 
and/or tolerability have been reached. This decision will be made after a discussion takes 
place between the sponsor study team and the investigator. The sponsor study team may not 
overrule the investigator’s decision to stop dose-escalation. If dose-escalation is stopped 
because of any of these criteria, additional cohorts may receive the same or lower doses of 
the study intervention.
The dose-escalation in Part 1 and separately in Part 2 will be terminated based on the 
following criteria:

If 50% or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant laboratory, ECG, 
or vital sign abnormalities, in the same organ class, indicating dose-limiting 
intolerance.

Severe nonserious AEs, considered as, at least, possibly related to study intervention
administration, in 2 participants at a given dose level (but not participants receiving 
placebo), independent of within or not within the same system organ class, indicating 
dose-limiting intolerance.

Dosing will be paused for any SAE that occurs in a participant receiving active 
treatment until causality is fully assessed by the PI and sponsor. Dosing may resume 
if the SAE is determined to be not drug-related by the PI and sponsor. If the SAE is 
determined to be either drug-related or unknown, either dosing will cease or the SAE 
will be evaluated by the sponsor’s protocol review committee (or similar review 
group), which is independent of the study team and investigators. If the protocol 
review committee determines that dosing may resume, a plan that mitigates risks to 
participants with the resumption of dosing will be implemented. Such a plan could
include a revision of inclusion/exclusion criteria, repeating or reducing the dose, or 
adding appropriate safety monitoring.

It is determined that the limit of safety and/or tolerability has been reached. This 
decision will be made following discussions between the study team and the 
investigator.


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
Other findings that, at the discretion of the study team and investigator, indicate that 
dose-escalation should be halted.

If, at any dose level, the average exposure reaches or exceeds the PK stopping limits
defined as the following: 

total Cmax=1450 ng/mL (in Part 1 and Part 2);

total AUC24=18,400 ng•h/mL (in Part 1);

total AUC24=3,680 ng•h/mL (in Part 2 with revision to this stopping limit to be 
considered, via a protocol amendment post formal interim analysis, based on 
observed data in Part 1 and Part 2 in this study).

If, based on the observed data, the group mean Cmax or AUC (based on total plasma 
concentration) of the next planned dose is projected to exceed the escalation limits, 
that dose will not be explored. Modified doses may be explored if they are not 
expected to exceed PK stopping criteria.
Progression to the next dose level will occur if the last dose was well tolerated and after 
satisfactory review of the available safety and PK data.

Part 1: A minimum of 6 participants (including at least 1 participant who received 
placebo) of the planned 8 participants to be dosed at each dose level must complete 
dosing and planned assessment to a minimum of 24 hours post dose. Safety, 
tolerability, and plasma PK data through at least 24 hours post dose for the prior dose 
level (along with cumulative data from all previously administered doses) will be 
reviewed in order to identify the next dose-level to escalate to in the next period.

Part 2: A minimum of 8 participants (including at least 1 participant who received 
placebo) of the planned 10 participants to be dosed at each dose level must complete 
the planned 14 days of dosing and planned safety/tolerability assessments to a 
minimum of 24 hours post dose on Day 14.

In addition, plasma PK data through at least 24 hours post dose on Day 7 (or at 
least 24 hours post dose on Day 14 if the observed t½ of PF-07202954 in Part 1 is 
greater than 30 hours) for the prior dose level (along with cumulative data from 
all previously administered doses) will be reviewed in order to identify the next 
dose-level to escalate to in the next period. 
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.


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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: AE, or some other (administrative) reason.
If study intervention is definitively discontinued, the participant will not remain in the study 
for further evaluation. See the SoA-Table A, SoA-Table B, and SoA-Table D for data to be 
collected at the time of discontinuation of study intervention.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
7.1.1. ECG Changes
A participant who meets either of the bulleted criteria below based on the average of 
triplicate ECG readings will be withdrawn from the study intervention. 

QTcF >500 msec.

Change from baseline: QTcF >60 msec.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE.
7.1.2. Potential Cases of Acute Kidney Injury
Abnormal values in SCr and SCysC concurrent with presence or absence of increase in BUN 
that meet the criteria below, in the absence of other causes of kidney injury, are considered 
potential cases of acute kidney injury and should be considered important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 µmol/L) in SCr level and increase of ≥30% in SCysC 
level relative to the participant’s own baseline measurement should trigger another 
assessment of SCr and SCysC as soon as practically feasible, preferably within 48 hours 
from awareness.


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If the second SCr assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 µmol/L] in 
SCr increase relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or 
≥35.4 µmol/L), and if the second SCysC assessment (after the first observation of 
≥30% increase relative to the participant’s baseline measurement) remains increased by 
≥30%, then further dosing of study intervention should be withheld. The participant should 
continue all safety assessments and adequate, immediate, diagnostic, and supportive 
measures taken to correct apparent acute kidney injury.
If a participant demonstrates concomitant SCr-based and SCysC-based eGFR decline of 
≥30% compared to the participants’ baseline concomitant SCr-based and SCysC-based 
eGFR, then the participant should not be further dosed and adequate, immediate, supportive 
measures including urgent evaluation by a nephrologist (preferably within 24 hours) 
with appropriate management and treatment as clinically indicated. Safety assessments
should be repeated weekly or as indicated by the nephrologist until the renal parameters are 
deemed to be stable by the nephrologist and/or PI.
If the participant cannot be seen by a nephrologist within 24 hours (as described 
above), then the participant should be sent to a local emergency room for evaluation 
and treatment as clinically indicated.
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
eGFR result (ie, ≥30% decline in concomitant SCr-based and SCysC-based eGFR). This 
evaluation may include laboratory tests, detailed history, and physical assessment. In addition 
to repeating SCr and SCysC, laboratory tests should include serum BUN, serum creatine 
kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, urinary indices, as well as UACR and UPCR. All cases confirmed on repeat 
testing as meeting the laboratory criteria for acute kidney injury (ie, increase in SCr and
increase in SCysC), with no other cause(s) of laboratory abnormalities identified, should be 
considered potential cases of drug-induced kidney injury irrespective of availability of all the 
results of the investigations performed to determine etiology of the abnormal SCr and/or 
SCysC. If ≥2 healthy participants in a given dose group (in each of the 3 Parts of the study, 
separately) are noted to have 2 consecutive decreases from baseline in eGFR of ≥30%, based 
on concomitant SCr-based and SCysC-based eGFR, then an assessment of whether the 
finding may be considered an adverse drug reaction should be undertaken.
7.2. Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;


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
Death;

Study terminated by sponsor;

Discretion of the investigator or sponsor for safety or behavioral reasons, or the 
inability of the participant to comply with the protocol-required schedule of study 
visits or procedures at a given study site.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA-Table A, SoA-Table B, and SoA-Table D for assessments to be 
collected at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed. The early discontinuation visit applies only to participants who are 
enrolled/randomized, and received at least 1 dose of the study intervention, and then are 
prematurely withdrawn from the study. Participants should be questioned regarding their 
reason for withdrawal. The participant will be permanently discontinued both from the study 
intervention and from the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.


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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
Study procedures and their timing are summarized in the SoA-Table A, SoA-Table B, 
SoA-Table C, and SoA-Table D. Protocol waivers or exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA-Table A, 
SoA-Table B, SoA-Table C, and SoA-Table D is essential and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.


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A participant who qualified for this protocol but did not enroll into an earlier cohort/group
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be performed without repeat collection, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.  If an 
in-dwelling IV catheter is used for purposes of blood collection, discard the first 
approximate 3 mL of volume in the catheter prior to initiating collection of
protocol-specified blood samples. 
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 envisioned to be 
approximately 465 mL (Part 1), 540 mL (Part 2), and 205 mL (Part 3). The actual 
collection times of blood sampling may change. Additional blood samples may be taken for 
safety assessments at times specified by Pfizer, provided the total volume taken during the 
study does not exceed 550 mL during any period of 60 consecutive days.
To prepare for study participation, participants will be instructed on the information outlined 
in Section 5.3 (related to Lifestyle Considerations) and Section 6.5 (regarding 
permitted/limited use of Concomitant Therapies) of this protocol.
8.1. Efficacy Assessments
No efficacy assessments are being undertaken in this study. 
8.2. Safety Assessments
Planned timepoints for all safety assessments are provided in the SoA-Table A, 
SoA-Table B, SoA-Table C, and SoA-Table D. Unscheduled clinical laboratory 
measurements may be obtained at any time during the study to assess any perceived safety 
issues.


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During the on-going COVID-19 pandemic, as applicable, consistent with the investigator
site(s) policy/SOPs, testing for SARS-CoV2 and safety monitoring of the participants will be 
implemented.
8.2.1. PEs
In this study, PEs are to be performed at nominal timepoints specified in the SoA-Table A, 
SoA-Table B, and SoA-Table D.

A complete PE 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 PE will include, at a minimum, assessments of general appearance, the 
respiratory and CV systems, and participant-reported symptoms.
PEs may be conducted by a physician, trained physician's assistant, or nurse practitioner as 
acceptable according to local regulation. 
Height and body weight will also be measured and recorded as per the SoA-Table A, 
SoA-Table B, and SoA-Table D.
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;

Assessment performed at approximately the same time of the day at each nominal 
timepoint, as much as practically possible;

And participants must also remove the contents of their pockets and remain still 
during measurement of weight. 
8.2.2. Vital Signs
In this study, assessment of vital signs (including BP and pulse rate) will occur at the 
nominal timepoints specified in the SoA-Table A, SoA-Table B, SoA-Table C, and 
SoA-Table D per the following specifications: 

Single, supine BP and pulse rate will be measured with the participant’s arm 
supported at the level of the heart, and recorded to the nearest mm Hg after ≥5 minute
of rest;

The same arm (preferably the dominant arm) will be used throughout the study;


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
Participants should be instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
8.2.3. 12-lead ECGs
Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) should be 
collected at times specified in SoA-Table A, SoA-Table B, SoA-Table C, and SoA-Table D
using an ECG machine that automatically calculates the HR and measures PR, QT, and QTcF
intervals and QRS complex. Alternative lead placement methodology using torso leads (eg,
Mason-Likar) is not recommended 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 ≥10 minutes in a supine position. 
In Part 1, during conduct of the study: Triplicate 12-lead ECGs will be obtained 
approximately 2 to 4 minutes apart; the average of the triplicate ECG measurements 
collected before dose administration on Day 1 of each period will serve as each participant’s 
baseline QTcF value; 

However, for purposes of the CSR, within-participant, time-matched assessment of 
each PF-07202954 dose relative to placebo, will be reported.
In Part 2, during conduct of the study and for purposes of reporting in the CSR: Triplicate
12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average of the 
triplicate ECG measurements collected at 0H prior to dosing on Day 1 will serve as each 
participant’s baseline QTcF value.
In Part 1 and Part 2, when triplicate, supine, 12-lead ECGs are collected, to ensure safety of 
the participants, a qualified individual at the investigator site will make comparisons to 
baseline measurements. Additional ECG monitoring will occur if a) the mean value from the 
triplicate measurements for any post dose QTcF interval is increased by ≥60 msec from the 
baseline and is >450 msec; or b) an absolute QTcF value is ≥500 msec for any scheduled 
ECG. If either of these conditions occurs, then a single ECG measurement must be repeated 
at least hourly until QTcF values from 2 successive ECGs fall below the threshold value that 
triggered the repeat measurement.


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In Part 3, during conduct of the study and for purposes of reporting in the CSR: Single,
12-lead ECGs obtained prior to dosing in each Period will serve as baseline for the given 
Period and to ensure safety of the participants, a qualified individual at the investigator site 
will make comparisons of post dose 12-lead ECGs to this baseline measurement. Additional 
ECG monitoring will occur if a) a post dose QTcF interval is increased by ≥60 msec from the 
baseline and is >450 msec; or b) an absolute QTcF value is ≥500 msec for any scheduled 
ECG. If either of these conditions occurs, then 2 additional ECGs will be collected 
approximately 2 to 4 minutes apart to confirm the original measurement. If the QTcF values 
from these repeated ECGs remain above the threshold value, then a single ECG must be 
repeated at least hourly until QTcF values from 2 successive ECGs fall below the threshold 
value that triggered the repeat measurement.
If a) a postdose QTc interval remains ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator); or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring. A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion 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 
QTcF 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 Section 10.7.
8.2.3.1. Continuous Cardiac Monitoring by Telemetry – in Part 1, only
All abnormal rhythms will be recorded and reviewed by the study physician/medical provider
for the presence of rhythms of potential clinical concern. The time, duration, and description 
of the clinically significant event will be recorded in the DCT. In addition, a printed record of 
the tracing(s) of the clinically significant rhythm(s) will be made and retained with other 
source documents.
Telemetry should be collected, as outlined in in SoA-Table A, using a centralized system that 
also allows for the storage and advanced analysis of all recorded data in order to preserve 
important events for future evaluations. Holter monitoring should not be used in parallel with 
continuous telemetry, unless it is the only means of data storage available at the investigator
site, or verifiable arrhythmia quantification is required. To establish a baseline, telemetry 
should be recorded for at least 2 hours before dosing in Period 1, only. This may be done 
immediately prior to dosing or at some 2-hour continuous interval in the 24-hour interval 
prior to dosing, as long as the recording is performed when the participant is awake.
Telemetry may be stopped within a reasonably short period of time prior to dosing, in order 
to avoid interference with study operations conducted immediately before dosing. However, 


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it is expected that the telemetry leads will be in place and the system connected prior to 
dosing.
8.2.4. Clinical Safety Laboratory Assessments
See Section 10.2 for the list of clinical safety laboratory tests to be performed and the 
SoA-Table A, SoA-Table B, SoA-Table C, and SoA-Table D for the timing and frequency.
All protocol-required laboratory assessments, as defined in Section 10.2, must be conducted 
in accordance with the laboratory manual and the SoA-Table A, SoA-Table B, SoA-Table C, 
and SoA-Table D. Unscheduled clinical laboratory measurements may be obtained at any 
time during the study to assess any perceived safety issues.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 14 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
Refer to Section 10.6 for suggested actions and follow-up assessments in the event of 
potential drug-induced liver injury.
Participants may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.2.5. Pregnancy Testing
Pregnancy tests may be urine or serum tests but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in all females at the times listed in 
SoA-Table A, SoA-Table B, and SoA-Table D. Following a negative pregnancy test result at 
screening, appropriate contraception must be commenced, and a second negative pregnancy 
test result will be required at the baseline visit prior the participant’s receiving the study 
intervention. Pregnancy tests will also be done whenever 1 menstrual cycle is missed during 
the active treatment period (or when potential pregnancy is otherwise suspected) and at the 
end of the study. Pregnancy tests may also be repeated if requested by IRBs/ECs or if 
required by local regulations. If a urine test cannot be confirmed as negative (eg, an 
ambiguous result), a serum pregnancy test is required. In such cases, the participant must be 
excluded if the serum pregnancy result is positive.


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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Section 10.3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
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). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including 
a minimum of 28 calendar days, except as indicated below, after the last administration of 
the study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator 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 definitively 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 AE or SAE after the participant has concluded 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has completed the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator must promptly report the SAE to 
Pfizer using the CT SAE Report Form.


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8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Section 10.3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begin after obtaining informed consent as described in Section 8.3.1 are recorded on 
the AE section of the CRF.
The investigator is to record on the DCT all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/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 given in Section 10.3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.


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The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then exposes his female 
partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
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
If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until at least 
28 days after the last dose of the study intervention.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

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.


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8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if:

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE. Such persons may 
include healthcare providers, family members, and other roles that are involved in the trial 
participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness regardless of whether there is an associated SAE. The information 
must be reported using the CT SAE Report Form. Since the information 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 is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
N/A.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
N/A.


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8.3.8. Adverse Events of Special Interest
N/A.
However, the potential risks based on completed nonclinical toxicity studies are summarized 
in Table 1 may, based on observed data from this study, lead to 1 or more of these potential 
risks being classified as AESIs in the future.
8.3.8.1. Lack of Efficacy
N/A. Assessment of efficacy is not planned in the study population.
8.3.9. Medical Device Deficiencies
N/A.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, at the wrong dosage strength, or 
inadvertent exposure.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
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.


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Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of PF-07202954 greater than 4000 mg in a 24-hour interval will be 
considered an overdose.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-07202954 (whichever 
is longer).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis as soon as practically possible but at least 
within 5 days from the date of the last dose of study intervention if requested by the 
medical monitor (determined on a case-by-case basis).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
8.5.1. Plasma for Analysis of PF-07202954 Concentrations – Parts 1, 2, and 3
Blood samples (4 mL), to provide sufficient plasma, will be collected into appropriately 
labeled tubes containing K2EDTA for measurement of plasma concentrations of 
PF-07202954 as specified in the SoA-Table A, SoA-Table B, SoA-Table C, and 
SoA-Table D.

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 – with the actual date and time (24-hour clock time) of each sample recorded;

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 
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
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 DCT;

Any deviation from the specified sample handling procedure resulting in 
compromised sample integrity will be considered a protocol deviation.
Samples will be used to evaluate the PK of PF-07202954. Samples collected for analyses of 
PF-07202954 plasma concentrations may also be used to evaluate safety or clinical activity 
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. These data 
will be used for internal exploratory purposes and will not be included in the CSR for this 
study.
Genetic analyses will not be performed on these plasma samples. Participant confidentiality 
will be maintained.
Samples collected for measurement of plasma concentrations of PF-07202954 will be 
analyzed using a validated analytical method in compliance with applicable SOPs.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage, or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor.
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that may unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of timepoints for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.5.2. Plasma for Qualitative Metabolite Profiling - Part 2, only
Blood samples (4 mL each) to provide sufficient plasma will be collected for metabolite 
screening into appropriately labeled tubes containing K2EDTA at times specified in the 
SoA-Table C. These samples may be used for metabolite identification and/or evaluation of 
the bioanalytical method. 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. These data may be used for internal exploratory 
purposes and will not be included in the CSR for this study.


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8.5.3. Urine for Analysis of PF-07202954 Concentrations – Part 2, only
Urine will be collected at times defined in the SoA-Table C.
Spot Urine Collection prior to dosing on Day 1, each participant will complete a forced 
void. Approximately 5 mL aliquot from this urine (“urine blank”) will be collected and 
stored frozen for measurement of PF-07202954 concentrations. This collection must occur 
prior to dosing on Day 1 but can be as early as first void on the morning and as late as 
5 minutes prior to dosing. 
For details regarding 24 hour urine collection on Day 14, refer to Section 8.8.3. 
All urine aliquots will be collected per detailed instructions offered in a laboratory manual. 
Urine samples will be analyzed using a validated analytical method in compliance with 
applicable SOPs.
The urine samples must be processed, stored, and shipped as indicated in the instructions 
provided in a laboratory manual to the investigator site to maintain sample integrity. Any 
deviations from the urine sample handling procedure (eg, sample collection and processing 
steps, interim storage, or shipping conditions), including any actions taken, must be 
documented and reported to the sponsor. On a case-by-case basis, the sponsor may make a 
determination as to whether sample integrity has been compromised. 
Any deviation from the specified sample handling procedure resulting in compromised 
sample integrity, will be considered a protocol deviation.
As part of understanding the PK of the study drug, urine samples may also be used to 
evaluate safety or clinical activity 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. These data will be used for internal exploratory purposes and will not 
be included in the CSR for this study.
 
 
 
 
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Management of Incidental Findings
An incidental finding is one unknown to the participant that has potential health or 
reproductive importance, which is discovered unexpectedly in the course of a research study
but is unrelated to the purpose and beyond the aims of the study.
The MRI images will be reviewed by the central review facility identified by the sponsor.
The purpose of this review is to evaluate images for purposes of quantifying amount of liver 
fat and liver volume. Central image review is not a complete medical review of the 
participant. If, during the central review process, an unexpected observation is identified and 
this finding could, in the opinion of the central reviewer, have a significant health or 
reproductive consequence, this finding may be shared with the study sponsor for disclosure 
to the PI. All follow-up testing and final diagnosis will be left to the discretion of the medical 
professionals at the site or those with an existing physician/-participant relationship. The PI
will be responsible for reporting any AEs identified from incidental findings as described in 
the AE reporting section. Identification of such incidental findings during the central review 
process should not be expected, and the site maintains responsibility for performing a general 
safety review of all images as per site protocols. 
Assessment of Liver Fat and Liver Stiffness – using FibroScan® - in Part 2, only 
In this study, assessments of liver fat and stiffness using FibroScan® will occur at scheduled 
visits outlined in the SoA-Table B. Each assessment will require the participants to be in a 
supine position for approximately 15 minutes with the image acquisition undertaken 
following a fast (except water) of ≥4 hours. The results for liver fat (via CAP™) in dB/m 
and liver stiffness (via VCTE™) in kPa will be displayed on the FibroScan® device at the end 
of each assessment and used to determine whether an individual participant qualifies to 
progress to dosing. Acquisition results do not need independent over-reading, but steps to 
ensure that acquisition was complete and accurate are required. Training is to be offered to at 
least 2 site staff (who may be sonographers or comparable) by Echosens and certified as 
operators based on this training by Echosens, at the start of the study. As much as practically 
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possible, attempts will be made to ensure each individual participants’ assessment is 
performed by the same site staff throughout the study.
The summary of numerical results (including quality related outputs) must be printed and 
saved by the study site (or imaging facility, as applicable) as part of each participant’s source 
documents. In addition, all images and output reports acquired must be saved by the study 
site until the conclusion of the study.
8.7. Genetics
8.7.1. Specified Genetics
A single 4 mL blood sample (in K2EDTA tube for DNA isolation) will be collected as 
outlined in SoA-Table A, SoA-Table C, and SoA-Table D. It will be analyzed to assess the 
impact of allelic variants of ABCG2 (encodes for BCRP), PNPLA3, and HSD17b13. 
Additionally, the sample may be used to evaluate other genetic variants for associations with 
variation in PK, clinical activity assessed as part of this study, or to explore AEs.
Genome-wide markers for controlling for ethnic-based genetic associations may also be 
assayed. 
If needed (eg, in the event of DNA extraction failure), a replacement blood sample may be 
requested from the participant.
See Section 10.5 for information regarding genetic research.
8.7.2. Banked Biospecimens for Genetics
A 2 mL blood sample optimized for DNA isolation (Prep D1.5) will be collected as local 
regulations and IRBs/ECs allow - as outlined in SoA-Table A, SoA-Table C, and
SoA-Table D. If collection is missed at the designated time point, the sample may be 
collected at the next available timepoint when biospecimens are being collected.
Banked Biospecimens may be used for research related to the study intervention(s) and 
NAFLD/NASH. Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be 
studied using the banked samples. 
If needed (eg, in the event of DNA extraction failure), a replacement blood sample may be 
requested from the participant.
See Section 10.5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the study-specific laboratory 
manual offered to the site(s) ahead of study initiation.
 
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8.8.3. Interval Urine Collection 
This sub-section covers details regarding interval urine collection for measurement of –
 
 
Over a 24-hour period, urine collection will be undertaken at times specified in the 
SoA-Table A, and SoA-Table C –
•
Each interval urine collection will start with a forced void which can be used for other 
spot urine assessments (or discarded):
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•
All subsequent urine voids through up to 0H on Day 1 (in the case of baseline with 
collection started at time-matched 0H on Day -1) and 24 hours post dose (on Day 14) 
will be collected and saved in a container and stored in refrigerated conditions 
(ie, 2-8°C) for the duration of the collection interval.
•
Each interval urine collection will end (ie, at 12H and 24H) with a forced void which is 
included as part of the interval urine collection:
•
If the end of the 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, as 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 a protocol deviation.
•
The urine will be mixed, and the total volume and weight will be recorded (for the 
intervals of 0-12H and 0-24H);
•
 
 
 
•
 
 
 
 
 
 
 
 
 
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8.9. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in an SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No formal hypothesis tests are planned for this study. 
9.2. Sample Size Determination
Part 1: A sample size of 8 participants per cohort for this single, dose-escalating, 4-period, 
cross-over, with placebo insertion study (6 active, 2 placebo per dose level) has been chosen 
based on the need to minimize first exposure to humans of a new chemical entity and the 
requirement to provide adequate safety and toleration information at each dose level.
Part 2: A sample size of 10 participants per cohort, with 8 participants randomized to 
PF-07202954 plus 2 participants to placebo per cohort, has been selected as a compromise 
between the need to minimize exposure to PF-07202954 and the need to have sufficient 
participants randomized to provide adequate safety and toleration information, PK, and 
ability to assess clinical pharmacology of PF-07202954 
 
 at each dose level.
Part 3 (if conducted): A sample size of 8 (minimum) to 12 (maximum) participants will 
provide adequate precision to estimate the AUCinf of PF-07202954 when it is administered 
with a high-fat/high-caloric meal (Test condition) as compared to PF-07202954 administered 
following an overnight fast (Reference condition). This sample size assumes that the 
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within-participant SD for log-transformed PK parameters would not increase beyond 
approximately 0.24. The probable 90% CI21 with 80% coverage probability for an effect size 
of 1.0 (ie, no change in exposure with and without food) for a range of SDs and sample sizes 
are provided in Table 6. The sample size ultimately decided for Part 3, by the sponsor, will 
depend on observed variability in plasma PK observed in Part 1.
Table 6.
Probable 90% CI with 80% coverage probability for Varying SDs and 
Sample Sizes – in Part 3
Sample Size
SD = 0.18
SD = 0.21
SD = 0.24
8
0.81 – 1.23
0.78 – 1.28
0.76 – 1.32
10
0.84 – 1.19
0.81 – 1.23
0.79 – 1.26
12
0.86 – 1.17
0.84 – 1.20
0.81 – 1.23
A total of up to 88 unique participants (16 in Part 1, initially 30-40 with expansion up to 
50 [with 5 cohorts] or 60 [with 6 cohorts] in Part 2, and a maximum of 12 in Part 3) are 
planned to be randomized in this study. Participants discontinuing prior to completion of the 
study for reasons other than safety may, at the discretion of the investigator and sponsor, be 
replaced by another participant who will –

If in Part 1, repeat all 4 Periods; but in rare circumstances, as guided by the need to 
ensure collection of sufficient placebo data, including within participant 
placebo-comparison, a decision may be made for the replacement participant to 
complete some and not all 4 Periods;

If in Part 2 or Part 3: repeat all dosing periods (ie, 14 days of dosing in Part 2 and
both Periods in Part 3) in order to ensure interpretable data.
9.3. Analysis Sets
For purposes of analysis, the analyses sets are defined as outlined in Table 7.
Table 7.
Definition of the Analyses Sets in Study C4171001
Participant Analysis Set
Description
Enrolled/Randomly 
assigned to study 
intervention
"Enrolled" means a participant's agreement to participate in a clinical study following 
completion of the informed consent process and randomization:

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.
Evaluable
All participants randomly assigned to study intervention and who take at least 1 dose of 
study intervention for the given Part (1, 2, or 3).
Safety
All participants randomly assigned to study intervention and who take at least 1 dose of 
study intervention. Participants will be analyzed according to the product they actually 
received.
PK Concentration
All participants who receive at least 1 dose of PF-07202954 and in whom at least 1 PK 
concentration is reported, for the given Part (1, 2, or 3).
PK Parameter
All participants who receive at least 1 dose of PF-07202954 and who have at least 1 of the 
PK parameters of interest calculated, for the given Part (1, 2, or 3).


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9.4. 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.
9.4.1. General Considerations
The data from each of the 3 Parts will be analyzed and reported separately in a single CSR 
issued at the end of this study. 
9.4.2. Primary Endpoint(s)
The primary endpoints in Part 1 and Part 2 are related to safety/tolerability with analyses as 
described in Section 9.4.5.
The primary endpoints in Part 3 are the plasma PK endpoints whose analyses are described in
Section 9.4.3.1 and Section 9.4.3.2.
9.4.3. Secondary Endpoint(s)
The secondary endpoints (in Part 1 and Part 2) as well as the primary endpoints (in Part 3) 
related to PK are described herein. 
9.4.3.1. PK Analysis
9.4.3.1.1. Derivation of PK Parameters
The PK parameters for PF-07202954 following oral dose administration will be derived from 
the concentration-time profiles as detailed in Table 8 [following single doses in Part 1 and 
Part 3] and Table 9 [following single and repeated doses in Part 2]. 
In all cases, actual PK sampling times will be used in the derivation of PK parameters.
Table 8.
Plasma PK Parameters for Part 1 (Single, Escalating Doses) and Part 3 
(Single Dose Food Effect, if Conducted)
Parameter
Definition
Method of Determination
AUClast
Area under the plasma 
concentration-time profile from 
time 0 to the time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUCinf*
Area under the plasma 
concentration-time profile from 
time 0 extrapolated to infinite time
AUClast + (Clast*/kel), where Clast* is the 
predicted plasma concentration at the last 
quantifiable timepoint estimated from the 
log-linear regression analysis
Cmax
Maximum observed concentration
Observed directly from data
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence
Tlag
Lag time 
Observed directly from data as time prior to the time 
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Table 8.
Plasma PK Parameters for Part 1 (Single, Escalating Doses) and Part 3 
(Single Dose Food Effect, if Conducted)
Parameter
Definition
Method of Determination
t1/2*
Terminal half-life
Loge (2)/kel, where kel is the terminal phase rate 
constant calculated by a linear regression of the 
log-linear concentration-time curve:
•
Only those data points judged to describe the 
terminal log-linear decline will be used in the 
regression.
CL/F*
Apparent clearance
Dose/AUCinf
Vz/F*
Apparent volume of distribution
Dose/(AUCinf kel)
*As data permit
Table 9.
Plasma and Urine PK Parameters for Part 2 (Repeated Escalating Doses)
Parameter
Day(s)
Definition
Method of Determination
Plasma
AUCtau
1, 7, 14
Area under the plasma concentration-time 
profile from time 0 to time τ (tau)
Linear/Log trapezoidal method
Cmax
1, 7, 14
Maximum observed concentration during 
the dosing interval
Observed directly from data
Tmax
1, 7, 14
Time for Cmax
Observed directly from data as time of first 
occurrence
Tlag
1, 7, 14
Lag time 
Observed directly from data as time prior to 
the time corresponding to the first 
quantifiable concentration
Cmin
7, 14
Minimum observed concentration during 
the dosing interval
Observed directly from data
Cav
7, 14
Average concentration
AUCtau/tau
PTR
7, 14
Peak-to-trough ratio
Cmax/Cmin
Rac,AUCtau
7, 14
Observed accumulation ratio
AUCtau (Day 7 or 14)/AUCtau (Day 1)
Rac,Cmax
7, 14
Observed accumulation ratio for Cmax
Cmax (Day 7 or 14)/Cmax (Day 1)
t1/2*
14
Terminal half-life
Loge(2)/kel,
• where kel is terminal phase rate constant 
calculated by a linear regression of 
log-linear concentration-time curve.
• only those data points judged to describe 
terminal log-linear decline will be used in 
the regression.
Vz/F*
14
Apparent volume of distribution
Dose/(AUCtau kel)
CL/F
7, 14
Apparent clearance
Dose/AUCtau
Urine
Aetau
14
Amount of unchanged drug recovered in 
urine during dosing interval
Sum of [urine concentration x urine 
volume] for each collection over the dosing 
interval
Aetau%
14
Percent of dose recovered in urine as 
unchanged drug over dosing interval
100 x Aetau/Dose
CLr
14
Renal clearance
Aetau/AUCtau
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9.4.3.2. Statistical Methods for PK Data
No formal inferential statistics will be applied to the plasma PK data from Part 1 and 2. In 
Part 3, if conducted, the statistical comparison of plasma PK under high-fat/high-caloric state 
(test) versus fasted (reference) condition is envisioned.
•
Part 1 (Single, Escalating Doses): Plasma concentrations of PF-07202954 will be 
descriptively summarized and plotted by nominal PK sampling time and dose:
•
The plasma PK parameters AUCinf, Cmax, AUClast, Tmax, Tlag, CL/F, Vz/F, and t½
will be summarized descriptively by dose;
 
 
 
 
 
•
Part 2 (Repeated, Escalating Doses): Plasma concentrations of PF-07202954 will be 
descriptively summarized and plotted by nominal PK sampling time, day, and dose:
•
The plasma PK parameters AUCtau, Cmax, Tmax, Tlag, t½, Cmin, Cav, PTR, CL/F, Vz/F, 
Rac,AUCtau, and Rac,Cmax, and the urine PK parameters Aetau, Aetau%, and CLr will be 
summarized descriptively by dose and day as applicable;
 
•
Median morning trough (predose) plasma concentrations will be plotted by day 
(all doses on the same plot) in order to assess the attainment of steady state.
•
Part 3 (Single-Dose Food Effect, if conducted): To compare PF-07202954
exposures following high-fat/high-caloric meal (Test) versus following an overnight 
fast (Reference) natural log-transformed Cmax, AUClast, and AUCinf (if data permit) 
will be analyzed using a mixed effects model with treatment as a fixed effect and 
participant as a random effect. Period may also be included as a factor in the model. 
Estimates of the adjusted mean differences (Test-Reference) and corresponding 
90% CIs will be obtained from the model. The adjusted mean differences and 
90% CIs for the differences will be exponentiated to provide estimates of the ratio of 
adjusted geometric means (Test/Reference) and 90% CIs for the ratios. 
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•
In addition –
•
Plasma concentrations of PF-07202954 will be descriptively summarized and 
plotted by nominal PK sampling time and treatment;
•
The plasma PK parameters AUCinf, Cmax, AUClast, Tmax, Tlag, CL/F, Vz/F, and 
t½ will be summarized descriptively by treatment;
•
For AUCinf, Cmax, and AUClast, box and whisker plots will be presented by 
treatment and overlaid with geometric means.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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a.
For a complete definition of all PK parameters refer to Table 8 and Table 9.
NOTE: For all non-PK related endpoints, baseline is defined as the time-matched data obtained while on placebo 
[Part 1], 0H assessment on Day 1 or 0-12H or 0-24H assessment prior to 1st dose [Part 2], or 0H assessment on Day 1 in 
each Period [Part 3], unless otherwise specified in the SAP.
9.4.4.1. Analysis of Measures of Clinical Activity
For these analyses, the Evaluable Set as defined in Table 7 will be utilized. 
Description of the analyses for the tertiary endpoints (refer to Table 10) will be outlined in 
the SAP.
9.4.5. Safety Analyses
9.4.5.1. Standard Safety Analyses
In this study, assessment of safety and tolerability following single- and repeated-, escalating 
doses forms the primary objective for Part 1 and Part 2. In all 3 Parts of the study, all safety 
analyses will be performed on the Safety Analysis Set.
All AEs, ECGs, BP, pulse rate, continuous cardiac monitoring, 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 PE and neurological examination information, as applicable, collected 
during the course of the study will be considered source data and will not be required to be 
reported, unless otherwise noted. However, any untoward findings identified on physical 
and/or neurological examinations conducted during the active collection period will be 
captured as AEs, if those findings meet the definition of an AE. Data collected at screening 
that are used for inclusion/exclusion criteria, such as laboratory data, ECGs, and vital signs,
will be considered source data, and will not be required to be reported, unless otherwise 
noted. Demographic data collected at screening will be reported.
9.4.5.2. 12-lead ECG Interval Analyses
Changes from baseline for the ECG parameters QT interval, HR, QTcF interval, PR interval, 
and QRS complex will be summarized by treatment and time.
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The number (%) of participants with maximum post dose QTcF values and maximum 
increases from baseline in the categories outlined in Table 11 will be tabulated by treatment.
Table 11.
Safety QTcF Assessment in Study C4171001
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
When more than 1 ECG is collected at a nominal time after dose administration (for 
example, triplicate ECGs), the mean of the replicate measurements will be used to represent a 
single observation at that timepoint. If any of the 3 individual ECG tracings has a QTcF
value >500 msec, but the mean of the triplicates is not >500 msec, the data from the 
participant’s individual tracing will be described in a safety section of the CSR in order to 
place the >500 msec value in appropriate clinical context. However, values from individual 
tracings within triplicate measurements that are >500 msec will not be included in the 
categorical analysis unless the average from the triplicate measurements is also >500 msec.
Changes from baseline will be defined as the change between the post dose QTcF value and
the average of the time-matched baseline triplicate values while on Placebo (in Part 1), the 
average of the triplicate collected at 0H prior to dosing on Day 1 (in Part 2), or the predose
value on Day 1 in each Period (in Part 3).
In addition, an attempt will be made to explore and characterize the relationship between 
plasma concentration and QT interval length using a PK/PD modeling approach. If a PK/PD 
relationship is found, the impact of participant factors (covariates) on the relationship will be 
examined.
 
 
 
 
 
9.5. Interim Analysis
As guided by observed safety/tolerability, PK, 
 of clinical activity, in 
Part 1 and Part 2 in this study, a formal interim analysis may be considered to evaluate 
potential revision to the currently proposed AUC24 PK stopping limit in Part 2 
(ie, AUC24=3,680 ng•h/mL).  This interim analysis will be used to evaluate whether repeated, 
escalating doses of PF-07202954 doses yielding exposures greater than the currently planned 
PK stopping limit in Part 2 are attempted. If data are supportive, studying higher exposures 
will be contingent on a protocol amendment which will undergo the required regulatory and 
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EC/IRB approvals. Before the interim analysis is instigated, the details of the objectives, the 
method of maintaining the study blind, and the analyses details will be documented in the 
SAP and/or IA charter.
As this is a sponsor-open study, a limited number of the sponsor’s team members (excluding 
site staff) may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating dose-escalation decisions, facilitating PK/PD 
modeling, and/or supporting clinical development.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC. 


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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 and 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.
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 guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
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 ICH GCP that the investigator becomes aware 
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10.1.2. Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study 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, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant. Participants who are rescreened are 
required to sign a new ICD.


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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research. The optional 
additional research does not require the collection of any further samples. The investigator or 
authorized designee will explain to each participant the objectives of the additional research.
Participants will be told that they are free to refuse to participate and may withdraw their 
consent at any time and for any reason during the storage period. A separate signature will be 
required to document a participant's agreement to allow specimens to be used for additional
research. Participants who decline to participate in this optional additional research will not 
provide this separate signature.
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 his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.


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10.1.6. 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.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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 (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, remote, or on-site monitoring), are provided in the IQMP.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
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.
10.1.7. 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 can be found in the Source Document Locator. 
Description of the use of computerized system is documented in the Source Document 
Locator.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 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 GCP guidelines;


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


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10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the CTMS.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent. The contact card contains, at a minimum, protocol and study intervention identifiers, 
participant numbers, contact information for the investigator site, and contact details for a 
contact center in the event that the investigator site staff cannot be reached to provide advice 
on a medical question or problem originating from another healthcare professional not 
involved in the participant’s participation in the study. The contact number can also be used 
by investigator staff if they are seeking advice on medical questions or problems; however, it 
should be used only in the event that the established communication pathways between the 
investigator site and the study team are not available. It is therefore intended to augment, but 
not replace, the established communication pathways between the investigator site and the 
study team for advice on medical questions or problems that may arise during the study. For 
sites other than a Pfizer CRU, the contact number is not intended for use by the participant
directly, and if a participant calls that number, he or she will be directed back to the 
investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
Table 12 delineates the protocol mandated safety-related laboratory tests 
 
of clinical activity to be collected following an overnight fast of ≥10 hours, unless 
otherwise specified, at timepoints defined in the SoA-Table A, SoA-Table B, SoA-Table C, 
and SoA-Table D.
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.
Investigators must document their review of each laboratory safety report.
Laboratory/analyte results that could unblind the study will not be reported to investigator 
sites or other blinded personnel until the study has been unblinded.
Table 12.
All Planned Protocol-Required Safety-Related Laboratory Tests 
in Study C4171001
Hematology
Chemistry
Urinalysis
−
Hemoglobin
−
Hematocrit
−
RBC count
−
MCV
−
MCH
−
MCHC
−
Platelet count
−
WBC count
−
Total neutrophils 
(Abs)
−
Eosinophils 
(Abs)
−
Monocytes (Abs)
−
Basophils (Abs)
−
Lymphocytes 
(Abs)
−
Reticulocytes 
(Abs)
−BUN
−SCr (and eGFR using CKD-EPI)
−Calcium
−Sodium
−Potassium
−Chloride
−Total CO2 (bicarbonate)
−AST (SGOT)
−ALT (SGPT)
−TBili
−ALP
−GGT
−Direct (conjugated) bilirubin
−Indirect (unconjugated) bilirubin
−Creatine Kinaseb
−Uric acid
−Albumin
−Total protein
−pH
−Glucose (qual)
−Protein (qual)
−Blood (qual)
−Ketones
−Nitrites
−Leukocyte esterase
−Urobilinogen
−Urine bilirubin
−UACR
−UPCR
−Microscopya
Other
• At Screen, only, in all 3 Parts –
−Serum FSH;c
−HBsAg, HBcAb, HCVAb, HIV.
• Serum pregnancy test (in all females; refer to Section 8.2.5).
• Urine drug test.d
CCI
CCI
CCI


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Table 12.
All Planned Protocol-Required Safety-Related Laboratory Tests 
in Study C4171001
 
 
Additional Tests for instances of suspected Hy’s Law[refer to Section 10.6]: 
−ALT, AST (repeat) 
−TBili (repeat) 
−Albumin (repeat)
−ALP (repeat)
−Direct bilirubin
−Indirect bilirubin
−CK
−GGT
−PT/INR
−Total bile acids
−Acetaminophen drug and/or protein adduct levels
a.
In Part 1 and Part 3 to be performed only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase; 
however, in Part 2 only, to be performed at all timepoints irrespective of results on urine dipstick (as it related to 
blood, protein, nitrites, or leukocyte esterase).
b.
Test to be assessed upon each admission (in Part 1, Part 2, and Part 3); but after initiation of study intervention, only
when ALT or AST is >ULN.
c.
In females amenorrhoeic ≥12 months, only, for confirmation of postmenopausal status only.
d.
Minimum requirements for urine drug test includes cocaine, opiates/opioids, benzodiazepines, and amphetamines.
For list of terms corresponding to the abbreviations used herein, refer to Section 10.8.
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 
or unexpected 
safety findings. 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.
CCI
CCI
CCI


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms;

Requires additional diagnostic testing or medical/surgical intervention;

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.


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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 


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baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious. The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product. The terms “suspected transmission” and “transmission” are 
considered synonymous. These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel. Such cases are also 
considered for reporting as product defects, if appropriate.


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10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety. 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. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under 
study during pregnancy 
or breastfeeding, and 
occupational exposure

All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding.

Occupational exposure is not
recorded.
All (and EDP supplemental form for 
EDP).
Note: Include all SAEs associated with 
exposure during pregnancy or 
breastfeeding. Include all AEs/SAEs 
associated with occupational exposure.

When an AE/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/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 


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the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 


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for every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this causal 
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the CT SAE Report Form and in accordance with the SAE 
reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data


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become available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.


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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention,
which corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

In addition to male condom use, a highly effective method of contraception is to be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3);
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with low user dependency, as described below during the 
intervention period and for at least 28 days after the last dose of study intervention,
which corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s). The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 


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10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female.

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, 

High FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 

Female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.


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10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
Highly Effective Methods That Have Low User Dependency [female participants and
female partners of male participants]
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days.
6. Sexual abstinence.

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
Highly Effective Methods [female partners of male participants, only]
1. Highly Effective Methods That Are User Dependent Combined (estrogen- and 
progestogen-containing) hormonal contraception associated with inhibition of 
ovulation.

Oral;

Intravaginal;

Transdermal;

Injectable.


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2. Progestogen-only hormone contraception associated with inhibition of ovulation.

Oral;

Injectable.
3. Sexual abstinence.

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the male participant.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).


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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, blood samples will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to PF-07202954/placebo or study interventions of this class 
to understand treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Samples for specified genetic analysis (see Section 8.7.1) will be stored for up to 
3 years after regulatory approval or other period as per local requirements, unless 
the study participant signs the Additional Consent Request permitting longer 
storage for optional additional research.

Samples for banking will be stored indefinitely or for another period as per local 
requirements.

Participants may withdraw their consent for the storage and/or use of their Banked 
Biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed. Data already generated from the samples will 
be retained to protect the integrity of existing analyses.

Banked Biospecimens will be labeled with a code. The key between the code and the 
participant’s personally identifying information (eg, name, address) will be held at the 
study site and will not be provided to the sample bank.


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


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, 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, 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 and liver imaging (eg, biliary tract) and collection of 
serum samples for acetaminophen/paracetamol drug and/or protein adduct levels may be 
warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive ventricular 
complexes.
ECG Findings That May Qualify as Serious Adverse Events

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia.

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented periods 
of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (heart 
rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to <100 bpm), and 


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monomorphic/polymorphic ventricular tachycardia (HR >100 bpm (such as
torsades de pointes)).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events

Change in pattern suggestive of new myocardial infarction.

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
AE
adverse event
AESI
adverse events of special interest
Aetau
amount of unchanged drug recovered in urine during the dosing interval
Aetau%
percent of dose recovered in urine as unchanged drug over the dosing interval
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the curve
AUC12
area under the curve over the time of 0-12 hours post dose
AUC24
area under the curve over the time of 0-24 hours post dose
AUCinf
area under the plasma concentration-time profile from time 0 extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time 0 to the time of the last 
quantifiable concentration
AUCtau
area under the plasma concentration-time profile from time 0 to time τ (tau), the dosing 
interval
AUEC24
area under the effect curve over the time of 0-24 hours post dose 
AV
atrioventricular
BBS
Biospecimen Banking System
BCRP
Breast cancer resistance protein
BMI
body mass index
BP
blood pressure
BUN
blood urea nitrogen
CAPTM
Controlled attenuation parameter (trademarked by EchoSens®)
Cav
average concentrations
CBP
childbearing potential 
Ceff
projected human effective plasma concentration
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CL
Clearance 
CL/F
apparent clearance
Clast
Last quantifiable plasma concentration
CLplasma
plasma clearance
CLr
renal clearance
Cmax
maximum observed plasma concentration
Cmin
minimum observed concentration
CNS
Central nervous system
CO2
carbon dioxide (bicarbonate)
COVID-19
Coronavirus Disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CT
clinical trial


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Abbreviation
Term
CTA
Clinical Trial Application 
CTMS
clinical trial management system
CV
Cardiovascular 
CYP
cytochrome P450
D/C
Premature discontinuation of participation post dosing on Day 1 from study
DAG
diacylglycerol
DCT
data collection tool
DDI
drug-drug interaction
DGAT
diacylglycerol acyltransferase
DGAT2i
diacylglycerol acyltransferase-2 inhibitor
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DNL
de novo lipogenesis
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
ED50
effective dose for 50% of the population
EDP
exposure during pregnancy
EDR
extemporaneous dispensing record
EFD
Embryofetal development 
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
Emax
maximum response achievable
EU
European Union
EudraCT
European Clinical Trials Database
F
oral bioavailability
FAMHP
Federal Agency for Medicines and Health Products
FDA
Food and Drug Administration
FFA
free fatty acid
FIH
first-in-human
FSH
follicle-stimulating hormone
fu
fraction unbound
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GLP
good laboratory practice
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HCC
hepatocellular carcinoma
HCVAb
hepatitis C antibody
hDGAT
human diacylglycerol acyltransferase 
HDL-C
high-density lipoprotein cholesterol
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
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Abbreviation
Term
IA
interim analysis
IB
Investigator’s Brochure
IC50
half maximal inhibitory concentration
IC85
maximal inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
IND
investigational new drug 
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IQMP
integrated quality management plan
IRB
institutional review board
IV
intravenous
K2EDTA
dipotassium ethylenediaminetetraacetic acid
ka
acid dissociation constant
Kel
terminal phase rate constant calculated by a linear regression of the log-linear 
concentration-time curve
LBBB
left bundle branch block
LDL-C
low-density lipoprotein cholesterol
LFT
liver function test
Loge
logarithm to the base of the mathematical constant e
MATE
multidrug and toxin extrusion
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR1
multidrug resistance protein 1
MGAT
monoacylglycerol acyltransferase
MR
magnetic resonance 
mRNA
messenger ribonucleic acid
N/A
not applicable
NAFLD
nonalcoholic fatty liver disease
NASH
nonalcoholic steatohepatitis
NOAEL
no-observed-adverse-effect level
NOEL
no-observed-effect level 
OAT1
organic anion transporter-1
OAT3
organic anion transporter 3
OCT2
organic cation transporter 2
PBPK model
physiologically-based pharmacokinetic model
PCRU
Pfizer clinical research unit
PD
pharmacodynamic(s)
PE
physical examination
P-gp
P-glycoprotein
PGx 
pharmacogenomic(s)
pH
potential of hydrogen
PI
Principal Investigator
PK
pharmacokinetic(s)
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Abbreviation
Term
pKa
Negative log of the acid dissociation constant 
PR interval
interval between the start of the electrocardiogram P wave and start of QRS complex, 
corresponding to time between onset of atrial depolarization and onset of ventricular 
depolarization
PT
prothrombin time
PTR
peak-to-trough ratio
PVC
premature ventricular contraction/complex
QRS
combination of 3 graphical deflections seen on a typical electrocardiogram
QT
time from electrocardiogram Q wave to end of T wave corresponding to electrical systole
QTc
corrected time from electrocardiogram Q wave to end of T wave corresponding to 
electrical systole
QTcF
corrected time from electrocardiogram Q wave to end of T wave corresponding to 
electrical systole (Fredericia method)
qual
qualitative
Rac
observed accumulation ratio
RBC
red blood cell
RNA
ribonucleic acid
RRCK
Ralph Russ Canine Kidney cell-based permeability assay
SAE
serious adverse event
SAP
statistical analysis plan
SAR-CoV2
Severe acute respiratory syndrome-coronavirus 2
SCr
serum creatinine
SD
standard deviation
SGOT
serum glutamic oxalo-acetic transaminase
SGPT
serum glutamic pyruvic transaminase
SoA
Schedule of Activities
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
t½
terminal half-life
TBili
total bilirubin
TG
triglyceride(s)
Tlag
lag time 
Tmax
time to achievement of maximum plasma concentration 
UACR
urinary albumin-to-creatinine ratio
ULN
upper limit of normal
UPCR
urinary protein-to-creatinine ratio
US
United States
US FDA
United States Federal Drug Administration 
UV
Ultraviolet 
VCTETM
Vibration-controlled transient elastography (trademarked by EchoSens®) 
VLDL
very low density lipoprotein
VLDL-C
very low density lipoprotein cholesterol
Vss
steady state volume of distribution
Vz/F
apparent volume of distribution
WBC
white blood cell
WOCBP
woman of childbearing potential
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11. REFERENCES
                                                
1
Yen CL, Stone SJ, Koliwad S, et al. Thematic review series: glycerolipids. DGAT 
enzymes and triacylglycerol biosynthesis. J Lipid Res 2008;49(11):2283-301.
2
Buhman KK, Smith SJ, Stone SJ, et al. DGAT1 is not essential for intestinal 
triacylglycerol absorption or chylomicron synthesis. J Biol Chem
2002;277(28):25474-9.
3
Cases S, Stone SJ, Zhou P, et al. Cloning of DGAT2, a second mammalian 
diacylglycerol acyltransferase, and related family members. J Biol Chem
2001;276(42):38870-6.
4
LaBrecque D, Abbas Z, Anania F, et al. Nonalcoholic fatty liver disease and 
nonalcoholic steatohepatitis. In: WGO Global Guidelines NAFLD/NASH (long 
version). Milwaukee, WI: World Gastroenterology Organisation; 2012: 29 pages.
5
Sanyal AJ, Friedman SL, McCullough AJ, et al. Challenges and opportunities in drug 
and biomarker development for nonalcoholic steatohepatitis: findings and 
recommendations from an American Association for the Study of Liver Diseases-U.S. 
Food and Drug Administration Joint Workshop. Hepatology 2015;61(4):1392-405.
6
Khan FZ, Perumpail RB, Wong RJ, et al. Advances in hepatocellular carcinoma: 
Nonalcoholic steatohepatitis-related hepatocellular carcinoma. World J Hepatol 
2015;7(18):2155-61.
7
Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic 
fatty liver disease – meta-analytic assessment of prevalence, incidence, and outcomes. 
Hepatology 2016;64(1):73-84.
8
Lambert JE, Ramos-Roman MA, Browning JD, et al. Increased de novo lipogenesis is a 
distinct characteristic of individuals with nonalcoholic fatty liver disease. 
Gastroenterology 2014;146(3):726-35.
9
Gluchowski NL, Gabriel KR, Chitraju C, et al. Hepatocyte deletion of triglyceride-
synthesis enzyme acyl CoA: diacylglycerol acyltransferase 2 reduces steatosis without 
increasing inflammation or fibrosis in mice. Hepatol 2019;70(6):1972-85.
10
Cassinotto C, Boursier J, de Ledinghen V, et al. Liver stiffness in nonalcoholic fatty 
liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver 
biopsy. Hepatology 2016;63(6):1817-27.


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11
Amin NB, Carvajal-Gonzalez S, Purkal J, et al. Targeting diacylglycerol acyltransferase 
2 for the treatment of nonalcoholic steatohepatitis. Sci Transl Med 
2019;11(520):eaav9701.
12
Saxena A, Chidsey K, Somayaji V, et al. Diacylglycerol acyltransferase 2 (DGAT2) 
inhibitor, PF-06865571, reduces liver fat by MRI-PDFF after 2 weeks in adults with 
NAFLD. Hepatology 2019;70(1 suppl):1260A-2127.
13
Motohashi H, Inui K. Organic cation transporter OCTs (SLC22) and MATEs (SLC47) 
in human kidney. AAPS J 2013;15(2):581-8.
 
 
15
Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from 
serum creatinine and cystatin C. N Engl J Med 2012;367(1):20-9.
 
 
 
 
 
 
 
 
21
Chow SC, Liu JP. Chapter 11. Population and individual bioequivalence. In: Design and 
analysis of bioavailability and bioequivalence studies. 3rd ed. Boca Raton, FL: Chapman 
& Hall/CRC; 2008: p. 335-75.
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SAP_001.pdf: 
Protocol C4171001 (PF-07202954) Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 1
TMF Doc ID: 98.03
Protocol C4171001
A PHASE 1, 3-PART, SPONSOR OPEN STUDY OF PF-07202954 IN HEALTHY 
ADULTS: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TO 
ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE (IN 
PART 1), AND REPEATED (IN PART 2), ESCALATING, ORAL DOSES ALONG 
WITH CONDITIONAL PART 3 OF RANDOMIZED, OPEN-LABEL ASSESSMENT 
OF EFFECT OF FOOD ON PF-07202954 EXPOSURE
Statistical Analysis Plan 
(SAP)
Version:
1  
Date:
19Mar2021  


Protocol C4171001 (PF-07202954) Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 2
TMF Doc ID: 98.03
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................3
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Objectives, Endpoints, and Estimands............................................................5
2.2. Study Design .............................................................................................................8
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ................................................................................................................10
3.1. Primary Endpoint(s) ................................................................................................10
3.2. Secondary Endpoint(s) ............................................................................................10
3.3. Other Endpoint(s)....................................................................................................10
3.3.1. Pharmacokinetic (PK) Endpoints ...............................................................10
3.4. Baseline Variables...................................................................................................14
3.5. Safety Endpoints .....................................................................................................14
3.5.1. Treatment Emergent Adverse Events.........................................................15
3.5.2. Laboratory Data..........................................................................................15
3.5.3. Vital Signs ..................................................................................................15
3.5.4. ECG ............................................................................................................16
3.5.5. Additional Safety Endpoints.......................................................................16
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................18
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................18
5.1. Hypotheses and Decision Rules ..............................................................................18
5.2. General Methods .....................................................................................................18
5.3. Methods to Manage Missing Data ..........................................................................20
5.3.1. Safety Data: ................................................................................................20
5.3.2. Pharmacokinetics Data: ..............................................................................20
5.3.3. Biomarker Endpoints..................................................................................21
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TMF Doc ID: 98.03
6. ANALYSES AND SUMMARIES ......................................................................................22
6.1. Primary Endpoint(s) ................................................................................................22
6.2. Secondary Endpoint(s) ............................................................................................22
6.4. Subset Analyses.......................................................................................................28
6.5. Baseline and Other Summaries and Analyses.........................................................28
6.5.1. Baseline Summaries....................................................................................28
6.5.2. Study Conduct and Participant Disposition................................................28
6.5.3. Concomitant Medications and Nondrug Treatments..................................28
6.5.4. Screening Data............................................................................................28
6.6. Safety Summaries and Analyses .............................................................................28
6.6.1. Treatment Emergent Adverse Events.........................................................29
6.6.2. Laboratory Data..........................................................................................29
6.6.3. Vital Signs ..................................................................................................29
6.6.4. Electrocardiograms.....................................................................................29
6.6.5. Additional Safety Endpoints.......................................................................30
7. INTERIM ANALYSES.......................................................................................................31
7.1. Introduction .............................................................................................................31
7.2. Interim Analyses and Summaries............................................................................32
8. REFERENCES ....................................................................................................................32
LIST OF TABLES
Table 1.  Summary of Changes..................................................................................................5
Table 2.  Key Objectives and Endpoints in Study C4171001....................................................5
Table 4. Plasma PK Parameters for Part 1 (Single, Escalating Doses) and Part 3 (Single 
Dose Food Effect, if Conducted)..............................................................10
Table 5. Plasma and Urine PK Parameters for Part 2 (Repeated Escalating Doses)...............11
Table 6.  Definition of the Analyses Sets in Study C4171001 ................................................18
Table 7. Plasma PK Parameters to be Summarized Descriptively ..........................................22
Table 8.  Urine PK Parameters to be Summarized Descriptively............................................22
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Protocol C4171001 (PF-07202954) Statistical Analysis Plan
PFIZER CONFIDENTIAL
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TMF Doc ID: 98.03
APPENDICES
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern .....33
Appendix 2. List of Abbreviations...........................................................................................34
Appendix 3. Bayesian Statistical Methodology Details ..........................................................36
Appendix 4. Thresholds for the observed Geometric Mean Ratio of the Composite 
Measure of Kidney Safety ........................................................................37


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PFIZER CONFIDENTIAL
Page 5
TMF Doc ID: 98.03
1. VERSION HISTORY
TABLE 1. SUMMARY OF CHANGES
Version/Date
Associated Protocol Amendment
Rationale
Specific Changes
1
19 March 2021
Protocol Amendment 1
01 Dec 2020 
N/A
N/A
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C4171001.  This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition or its analysis will also be reflected in a protocol amendment.
2.1. Study Objectives, Endpoints, and Estimands
Table 2 outlines the key objectives and endpoints for Part 1, Part 2, and Part 3 (if conducted) 
of this study. There are no estimands for this study.
TABLE 2.  KEY OBJECTIVES AND ENDPOINTS IN STUDY C4171001
Study 
Objectives
Endpoints 
Part 1
Primary 
To evaluate safety and tolerability 
of single, oral, escalating doses of 
PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants.
Following assessments over ≥10 days of each Period 
and up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG. 
Secondary 
To characterize the plasma PK
profile of PF-07202954 following 
administration of single, oral, 
escalating doses. 
PK parametersa derived from plasma PF-07202954 
concentrations: 
Cmax, Tmax, AUClast, AUCinf, t½, as data permit.
Part 2
Primary 
To evaluate safety and tolerability 
of repeated, oral, escalating doses 
of PF-07202954 administered with a 
standard morning meal in healthy, 
adult participants with simple 
hepatic steatosis.
Following assessments over the duration of dosing and
up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG. 
Secondary
To characterize the plasma and 
urine PK profiles of PF-07202954 
following administration of 
repeated, oral, escalating doses. 
PK parametersa derived from plasma PF-07202954 
concentrations: 

Single dose: Cmax, Tmax, AUCtau on Day 1.


Repeated dose: 

Days 7 and 14 – Cmax, Tmax, AUCtau, as data 
permit.

Day 14 – t½ as data permit.


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TABLE 2.  KEY OBJECTIVES AND ENDPOINTS IN STUDY C4171001
Study 
Objectives
Endpoints 
PK parametersa derived from urine PF-07202954 
concentrations on Day 14: Aetau, Aetau%, CLr.
Part 3, if conducted 
Primary 
To characterize the effect of a 
high-fat/high-caloric meal, 
compared to following an overnight 
fast, on plasma PK profile of 
PF-07202954 following 
administration of a single oral dose 
to healthy adults.
PK parametersa derived from plasma PF-07202954 
concentration: 
Cmax, Tmax, AUClast, and AUCinf, as data permit.
Secondary
To evaluate safety and tolerability 
of a single, oral, dose of 
PF-07202954 administered with a 
high-fat/high-caloric meal compared 
to following an overnight fast.
Following assessments over ≥5 days of each Period and
up to Day 30 ±2 days post last dose of study 
intervention –
AEs;
Clinical laboratory tests;
Vital signs (including BP and pulse rate);
Cardiac conduction intervals via 12-lead ECG.
a.
For a complete definition of all PK parameters refer to Table 4 and Table 5.
NOTE: For all non-PK related endpoints, baseline is defined as the time-matched data obtained while on placebo 
[Part 1], 0H assessment on Day 1 or 0-12H or 0-24H assessment prior to 1st dose [Part 2], or 0H assessment on Day 1 in 
each Period [Part 3]. Any deviations to these definitions are described in Section 3 of this SAP.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.
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a.
For a complete definition of all PK parameters refer to Table 4 and Table 5.
NOTE: For all non-PK related endpoints, baseline is defined as the time-matched data obtained while on placebo [Part 1], 
0H assessment on Day 1 or 0-12H or 0-24H assessment prior to 1st dose [Part 2], or 0H assessment on Day 1 in each Period 
[Part 3]. Any deviations to these definitions are described in Section 3 of this SAP.
2.2. Study Design
The study is planned as a 3-part design with investigator- and participant-blinded 
(sponsor-open), placebo-controlled, randomized, dose-escalation in Part 1 and Part 2; and a 
randomized, open-label design, in Part 3 (if conducted). Participants will receive oral dose(s) 
of PF-07202954 and/or placebo in this study. A total of up to 88 unique participants (16 in 
Part 1, up to 30-40 initially in Part 2 [and potential expansion to 50-60 post formal IA and 
protocol amendment], and a maximum of 12 in Part 3) are planned to be randomized in this 
study. 
The set-up of each of the 3 Parts of this study are summarized in Figure 1 (Part 1), Figure
2 (Part 2) and Figure 3 (Part 3). 
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Figure 1.
Overall Study Design - Part 1
Figure 2.
Overall Study Design - Part 2
Figure 3.
Overall Study Design - Part 3 [if conducted]
Part 1: Sample size (N) = 16 participants
Randomized, double-blind (Sponsor-open), 4-period, inter-leaving, placebo-controlled, single, oral dose, escalating design
Screen to dosing on Day 1 in Period 1: maximum of 28 days
Inpatient stay in each Period: Day -1 to minimum of Day 4 (ie, 72H post dose)
In each Period, 6 participants randomized to receive PF-07202954, and 2 participants will receive matching-placebo with standard morning meal
Intervals of ≥x-days reflect number of days between dosing either between Cohorts (ie, ≥5-days) or within a given Cohort (ie, ≥10-days) 
On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention 
Cohort 1
(n=8) 
Cohort 2
(n=8) 
On-site
Follow-up visit 
Period 1
Dose #1
Period 2
Dose #3
Period 3
Dose #5
Period 1
Dose #2
Period 2
Dose #4
Period 3
Dose #6
Period 4
Dose #7
Period 4
Dose #8
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥5-days
≥10-days
≥10-days
≥10-days
≥10-days
≥10-days
≥10-days
Follow-up visit
Screen
Screen
Screen to Day 1: maximum of 28 days includes double confirmation of CAP ≥ 270 dB/m and VCTE < 7 kPa on FibroScan® on separate days
Inpatient stay: Day -2 to Day 17 (19 consecutive days with 18 nights) 
Baseline for safety (at 0H prior to dosing on Day 1), other markers of clinical activity (on Day -1), 
In each cohort, 8 participants will be randomized to receive PF-07202954, and 2 participants will receive placebo
Once-daily dosing to occur from Day 1 to Day 14, inclusive, with a standard morning meal
On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention
Part 2: Sample size (N) = 50 in 1st planned 5 Cohorts and up to 60 including 1 optional Cohort of participants 
Randomized, double-blind (Sponsor-open), placebo-controlled, sequential, repeated, oral dose, escalating design
Cohort 3 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 4 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 5 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 6 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 7 
(n=10) 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Cohort 8 
(n=10)
Optional 
Screen 
Inpatient Stay
On-site 
Follow-up visit
Follow-up visit
Screen to Day 1 in Period 1: maximum of 28 days
Inpatient stay: Continuous from Day -1 (in Period 1) to Day 4 (in Period 2) – a total of 10 days and 9 nights 
On-site Follow-up visit to occur 8±2 days, with an additional telephone contact at 30±2 days, post last dose of study intervention
Part 3 [if conducted]: Sample size (N) = ≤ 12 participants 
Randomized, open-label, 2-period, crossover, single oral dose of PF-07202954 administered with and without high-fat/high-caloric meal 
Period 1
Day 1
Period 2
Day 1
≥5-days
On-site 
Follow-up visit
Inpatient Stay
Follow-up visit
Screen 
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3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
As listed in Section 2.1 the primary endpoints in Part 1 and Part 2 are related to 
safety/tolerability which are described in Section 3.5. The primary endpoints in Part 3 are the 
plasma PK endpoints which are described in Section 3.3.
3.2. Secondary Endpoint(s)
The secondary endpoints (in Part 1 and Part 2) are related to PK and are described in Section 
3.3. The secondary endpoints in Part 3 are related to safety/tolerability which are described in 
Section 3.5.
3.3. Other Endpoint(s)
3.3.1. Pharmacokinetic (PK) Endpoints
The PK parameters for PF-07202954 following oral dose administration will be derived from 
the plasma concentration-time profiles and urine concentrations as detailed in Table 4
[following single doses in Part 1 and Part 3] and Table 5 [following single and repeated doses 
in Part 2]. 
In all cases, actual PK sampling times will be used in the derivation of PK parameters. In the 
event that the actual sampling time is not available, the nominal time may be used if there is 
no evidence that the actual sampling time deviates substantially from the nominal time.
TABLE 4. PLASMA PK PARAMETERS FOR PART 1 (SINGLE, ESCALATING DOSES) AND 
PART 3 (SINGLE DOSE FOOD EFFECT, IF CONDUCTED)
Parameter
Definition
Method of Determination
AUClast
Area under the plasma 
concentration-time profile from 
time 0 to the time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUCinf*
Area under the plasma 
concentration-time profile from 
time 0 extrapolated to infinite time
AUClast + (Clast*/kel), where Clast* is the 
predicted plasma concentration at the last 
quantifiable timepoint estimated from the 
log-linear regression analysis
Cmax
Maximum observed concentration
Observed directly from data
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence
Tlag
Lag time 
Observed directly from data as time prior to the time 
corresponding to the first quantifiable concentration.
t1/2*
Terminal half-life
Loge (2)/kel, where kel is the terminal phase rate 
constant calculated by a linear regression of the 
log-linear concentration-time curve:

Only those data points judged to describe the 
terminal log-linear decline will be used in the 
regression.
CL/F*
Apparent clearance
Dose/AUCinf
Vz/F*
Apparent volume of distribution
Dose/(AUCinf × kel)
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TABLE 4. PLASMA PK PARAMETERS FOR PART 1 (SINGLE, ESCALATING DOSES) AND 
PART 3 (SINGLE DOSE FOOD EFFECT, IF CONDUCTED)
Parameter
Definition
Method of Determination
*As data permit
TABLE 5. PLASMA AND URINE PK PARAMETERS FOR PART 2 (REPEATED ESCALATING 
DOSES)
Parameter
Day(s)
Definition
Method of Determination
Plasma
AUCtau
1, 7, 14
Area under the plasma concentration-time 
profile from time 0 to time τ (tau)
Linear/Log trapezoidal method
Cmax
1, 7, 14
Maximum observed concentration during 
the dosing interval
Observed directly from data
Tmax
1, 7, 14
Time for Cmax
Observed directly from data as time of first 
occurrence
Tlag
1, 7, 14
Lag time 
Observed directly from data as time prior to the 
time corresponding to the first quantifiable 
concentration
Cmin
7, 14
Minimum observed concentration during 
the dosing interval
Observed directly from data
Cav
7, 14
Average concentration
AUCtau/tau
PTR
7, 14
Peak-to-trough ratio
Cmax/Cmin
Rac,AUCtau
7, 14
Observed accumulation ratio
AUCtau (Day 7 or 14)/AUCtau (Day 1)
Rac,Cmax
7, 14
Observed accumulation ratio for Cmax
Cmax (Day 7 or 14)/Cmax (Day 1)
t1/2*
14
Terminal half-life
Loge(2)/kel,
where kel is terminal phase rate constant 
calculated by a linear regression of log-linear 
concentration-time curve.
only those data points judged to describe 
terminal log-linear decline will be used in the 
regression.
Vz/F*
14
Apparent volume of distribution
Dose/(AUCtau × kel)
CL/F
7, 14
Apparent clearance
Dose/AUCtau
Urine
Aetau
14
Amount of unchanged drug recovered in 
urine during dosing interval
Sum of [urine concentration x urine volume] 
for each collection over the dosing interval
Aetau%
14
Percent of dose recovered in urine as 
unchanged drug over dosing interval
100 x Aetau/Dose
CLr
14
Renal clearance
Aetau/AUCtau
*As data permit
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3.4. Baseline Variables
Baseline variables are those collected only prior to dosing. In this study baseline variables are 
the demographic data of age, race, weight, and body mass index which will be collected at 
screening and summarized by treatment in accordance with the sponsor reporting standards.
3.5. Safety Endpoints
The primary assessments include the standard safety endpoints listed below (see the protocol 
for collection days and list of parameters):
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
Treatment-emergent AEs;

Clinical laboratory tests;

Vital signs (including BP and pulse rate);

Cardiac conduction intervals via 12-lead ECG.
These endpoints will be summarized according to CDISC standards described in the CDISC 
Safety Rulebook1.
3.5.1. Treatment Emergent Adverse Events
Any events occurring following start of treatment (either PF-07202954 or placebo) will be 
counted as treatment emergent. Events that occur in a non-treatment period (i.e. follow-up) 
within the lag time of 28 days will be counted as treatment emergent and attributed to the 
previous treatment taken. Similarly, the time period for collecting AEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent. 
3.5.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol.
To determine if there are any clinically significant laboratory abnormalities, the 
haematological, clinical chemistry (serum) and urinalysis safety tests will be assessed against 
the criteria specified in the sponsor reporting standards.  Post-baseline assessments will not 
take into account whether each subject’s baseline test result is within or outside the 
laboratory reference range for the particular laboratory parameter.
Baseline is defined as the time-matched data obtained while on placebo [Part 1], 
0H assessment on Day 1 [Part 2], or closest to 0H assessment prior to dosing on Day 1 in 
each Period [Part 3]. Results from only the planned study visits will be considered for 
baseline assessment.
3.5.3. Vital Signs
Single supine blood pressure and pulse measurements will be taken at all time points listed in 
the Schedule of Activities given in the protocol. Baseline is defined as the time-matched data 
obtained while on placebo [Part 1], 0H assessment on Day 1 [Part 2], or 0H assessment on 
Day 1 in each Period [Part 3].   
The following vital signs endpoints will be determined for each subject:

The maximum decrease and increase from baseline over all measurements taken postdose 
for systolic and diastolic blood pressures.

The maximum increase from baseline over all measurements taken postdose for pulse 
rate.
The maximum increase from baseline will be calculated by first subtracting the baseline value from each 
postdose measurement to give the change from baseline.  The maximum of these values over the respective 
period (Part 1 and Part 3) or entire study (Part 2) will then be selected, except in the case where a subject does 
not show an increase.  In such an instance, the minimum decrease should be taken.  Similarly, the maximum 


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decrease from baseline will be determined by selecting the largest negative value of the changes from baseline.  
In cases where a subject does not show a decrease, the minimum increase should be taken.
3.5.4. ECG
Single and triplicate 12-lead ECGs will be obtained on all subjects at times detailed in the 
Schedule of Activities given in the protocol.  The average of the triplicate readings collected 
at each assessment time will be calculated for each ECG parameter.  Baseline is defined as 
the average of the time-matched triplicate data obtained while on placebo [Part 1], the 
average of the triplicate collected at 0H assessment prior to dosing on Day 1 [Part 2], or the 
0H predose assessment on Day 1 in each Period [Part 3].
The QT, QTcF, PR, QRS and heart rate will be recorded at each assessment time.
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula:
QTcF = QT / (RR)1/3
where RR = 60/HR (if not provided)
The maximum absolute value (postdose) and the maximum increase from baseline for QTcF, 
PR and QRS, will be determined over all measurements for each subject.
The maximum increase from baseline will be calculated by firstly subtracting the baseline 
value from each postdose measurement to give the change from baseline.  The maximum of 
these values over the respective period (Part 1 and Part 3) or entire study (Part 2) will then be 
selected, except in the case where a subject does not show an increase.  In such an instance, 
the minimum decrease should be taken.
 
 
 
 
 
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4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
For purposes of analysis, the analyses sets are defined as outlined in Table 6.
TABLE 6.  DEFINITION OF THE ANALYSES SETS IN STUDY C4171001
Participant Analysis Set
Description
Enrolled/Randomly 
assigned to study 
intervention 
"Enrolled" means a participant's agreement to participate in a clinical study 
following completion of the informed consent process and randomization:

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.
Evaluable
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention for the given Part (1, 2, or 3).
Safety
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention for the given Part (1, 2 or 3). Participants will be 
analyzed according to the product they actually received.
PK Concentration
All participants who receive at least 1 dose of PF-07202954 and in whom at 
least 1 PK concentration is reported, for the given Part (1, 2, or 3).
PK Parameter
All participants who receive at least 1 dose of PF-07202954 and who have at 
least 1 of the PK parameters of interest calculated, for the given Part (1, 2, or 
3).
  
5. GENERAL METHODOLOGY AND CONVENTIONS
This is a 3-part sponsor-open study with Part 1 and Part 2 as investigator and participant 
blinded.  Specific Pfizer personnel (analytical staff, medical monitor, clinical leads,
clinicians, statistician, programmers, data managers and pharmacokineticists and people 
shadowing these team members) will be unblinded to participant treatments in order to 
permit real-time interpretation of the safety and PK data.  Treatment randomization 
information will be kept confidential by Pfizer personnel and will not be released to the 
investigator/site staff until the conclusion of the study.  Final analysis will follow the official 
database release after completion of all parts of the study.
5.1. Hypotheses and Decision Rules
There are no statistical hypotheses or decision rules.
5.2. General Methods
Descriptive Statistics
Descriptive statistics, including the sample size, mean, standard deviation, median, 
minimum, and maximum values, will be provided for continuous endpoints.  For 
binary/categorical variables the number and proportion of participants achieving the
thresholds will be presented.  Some measures will be summarized using graphical 
representations by treatment and study day of visit, where appropriate.
Mixed Effect Analysis of Variance (ANOVA)


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The mixed effect ANOVA model will be used to assess the food effect in Part 1 or Part 3, 
For endpoints in Part 1 of the study 
treatment group will be the fixed effect and participant will be the random effect.  In Part 3, 
sequence, period and treatment will be the fixed effects and participant within sequence will 
be the random effect. Estimates of treatment effects will be assessed using the least square 
means (LSMs) and 80% Confidence Intervals (CIs).  Estimates of the mean differences 
between each active dose and placebo, and the corresponding 80% CI will be obtained from 
the model.  If there are major deviations from the statistical assumptions underlying this 
model then non-parametric analyses may be presented.  
Analysis of Covariance (ANCOVA)
The ANCOVA model will be used with continuous endpoints for landmark (single time
point) analyses.  The model will include treatment group as a fixed effect, baseline value of 
the endpoint being analyzed as a covariate.  Study site and interaction of study site with 
treatment will be considered to be included as potential covariates for the analysis of whole 
liver fat only.  Estimates of treatment effects will be assessed using the least square means 
(LSMs) and 80% Confidence Intervals (CIs).  Estimates of the mean differences between 
each active dose and placebo, and the corresponding 80% CI will be obtained from the 
model.  If there are major deviations from the statistical assumptions underlying this model 
then alternative transformations or non-parametric analyses may be presented.  Justification 
for any alternative to the planned analysis will be given in the study report.
Mixed Model for Repeated Measurements (MMRM)
This model will be used for the analysis of endpoints with more than one post-baseline 
collection time point.  All observed data collected during the post-baseline treatment period
up to and including 1st Follow-up visit (conducted onsite) in Part 2 will be utilized; data 
collected during the follow-up period will be excluded.  Early discontinuation data will also 
be excluded. The MMRM analysis will be performed with treatment, study day and 
treatment-by-study day interaction as fixed effects, baseline value as a covariate.  Repeated 
measures model with unstructured correlation matrix will be utilized.  Time will be fitted as a 
repeated effect. If this does not converge then compound symmetry structure will be 
considered. Estimates of treatment effects will be assessed using LSMs and 80% CIs at each 
time point.  LSM difference between each dose of PF-07202954 and placebo group along 
with the 80% CIs and 2-sided p-values will be provided.  If there are major deviations from 
the statistical assumptions underlying this model then alternative transformations (e.g. log) or 
non-parametric analyses may be presented. Justification for any alternative to the planned 
analysis will be given in the study report.
Non-parametric Analysis
If the data have many outliers even after the log-transformation the following non-parametric 
analysis will be performed instead of the linear model.  An outlier will be defined as any 
datapoint falling outside of 3.5 × standard deviations +/- the median.  Additional evaluative 
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statistics will be conducted to explore the nature of the outliers in order to determine the 
appropriateness of a parametric analysis. 
For group medians 80% CIs will be presented.  In addition, the 80% CIs will also be 
presented for differences in group medians from placebo group median.  The method of 
McGill, Tukey, and Larson2 will be employed to calculate the CI for the difference in 
treatment group medians.
Dose Response Modeling
Data permitting a 4-Parameter Emax model will be used to characterize the %change from 
baseline dose-response relationship of whole liver fat in Part 2. The model structure will take 
the form: 
E0 is the placebo effect, dose is the target randomized dose, Emax is the maximum effect, ED50
is the dose producing 50% of the maximum effect and Hill is the slope parameter. 
The natural log transformed relative ratio from baseline response at the end of treatment 
period will be modeled with dose as a continuous variable and natural log transformed 
baseline whole liver fat as a covariate.  The model will be applied to the LSMean results 
from the primary ANCOVA model utilizing a Bayesian methodology with weakly 
informative priors as described in Appendix 3. The posterior means and 80% credible 
intervals of the placebo-adjusted effect estimates at each dose will be exponentiated to obtain 
the predicted values of %change from baseline.  Estimates of the model parameters of E0,
Emax, ED50 and slope and their 80% credible intervals will also be produced. In addition, the 
doses that result in 25% and 30% liver fat lowering will be identified along with their 80% 
credible intervals.
If convergence cannot be obtained or visual inspection of the data does not support a dose-
response Emax relationship the following options will be considered in order: (1) assume the 
hill parameter is 1 and remove from the model (giving a 3-parameter dose-response Emax
model) or (2) utilize alternative priors to those provided in the appendix.
5.3. Methods to Manage Missing Data
5.3.1. Safety Data:
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied. 
5.3.2. Pharmacokinetics Data:
Methods to handle missing PK data are described below.


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Concentrations Below the Limit of Quantification:
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings, BLQ values will be reported as “<LLQ”, where LLQ
will be replaced with the value for the lower limit of quantification.)
Deviations, Missing Concentrations and Anomalous Values:
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample),
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
Pharmacokinetic Parameters:
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a subject’s concentration data, the parameter will be coded as NC (ie,
not calculated). (Note that NC values will not be generated beyond the day that a subject 
discontinues.) In summary tables, statistics will be calculated by setting NC values to
missing; and statistics will be presented for a particular dose with ≥3 evaluable 
measurements or at least 50% of the data are available depending on the parameter.
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as vomiting before all the compound is adequately absorbed from 
the gastrointestinal tract), this will be footnoted in summary tables and will not be included in 
the calculation of summary statistics or statistical analyses.
 
 
 
 
 
 
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6. ANALYSES AND SUMMARIES
The data from each of the 3 Parts will be analyzed and reported separately in a single CSR 
issued at the end of this study. 
6.1. Primary Endpoint(s)
The primary endpoints in Part 1 and Part 2 are related to safety/tolerability whose analyses 
are described Section 6.6.
The primary endpoints in Part 3 are the plasma PK endpoints whose analyses are described in
Section 6.2.
6.2. Secondary Endpoint(s)
The secondary endpoints (in Part 1 and Part 2) as well as the primary endpoints (in Part 3) 
are related to PK and are described herein. The following analyses will utilize the PK 
Concentration and PK Parameter analyses sets defined in Table 6 in Section 4.
No formal inferential statistics will be applied to the plasma PK data from Part 1 and 2. In 
Part 3, if conducted, the statistical comparison of plasma PK under high-fat/high-caloric state 
(test) versus fasted (reference) condition is envisioned.
Plasma parameters will be summarized using the descriptive statistics specified in Table 7
and urine PK parameters will be summarized using the statistics specified in Table 8.
TABLE 7. PLASMA PK PARAMETERS TO BE SUMMARIZED DESCRIPTIVELY
Parameter
Summary Statistics
AUCinf, AUClast, Cmax, AUCinf(dn), 
AUClast(dn), AUCtau, AUCtau(dn), 
Cmax(dn), CL/F, Vz/F, Cmin, PTR, 
AUCtau, Cav, Rac,AUCtau, and Rac,Cmax
N, arithmetic mean, median, %CV, standard 
deviation (SD), minimum (min), maximum (max), 
geometric mean and geometric %CV
Tmax, Tlag
N, median, min, max.
t½
N, arithmetic mean, median, %CV, SD, min, max.
TABLE 8.  URINE PK PARAMETERS TO BE SUMMARIZED DESCRIPTIVELY 
Parameter
Summary Statistics
Aetau, Aetau% and CLr
N, arithmetic mean, median, %CV, SD, min, max, geometric 
mean and geometric %CV.

Part 1 (Single, Escalating Doses):

Plasma concentrations of PF-07202954 will be descriptively summarized and plotted by 
nominal PK sampling time and dose.


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
The plasma PK parameters AUCinf, Cmax, AUClast, Tmax, Tlag, CL/F, Vz/F, and t½ will be 
summarized descriptively by dose;
 
 
 
 
 
 

Part 2 (Repeated, Escalating Doses):

Plasma concentrations of PF-07202954 will be descriptively summarized and plotted by 
nominal PK sampling time, day, and dose:

The plasma PK parameters AUCtau, Cmax, Tmax, Tlag, t½, Cmin, Cav, PTR, CL/F, Vz/F, 
Rac,AUCtau, and Rac,Cmax, and the urine PK parameters Aetau, Aetau%, and CLr will be 
summarized descriptively by dose and day as applicable;
 
 

Median morning trough (predose) plasma concentrations will be plotted by day (all doses 
on the same plot) in order to assess the attainment of steady state.

Part 3 (Single-Dose Food Effect, if conducted): To compare PF-07202954 
exposures following high-fat/high-caloric meal (Test) versus following an overnight 
fast (Reference) natural log-transformed Cmax, AUClast, and AUCinf (if data permit) 
will be analyzed using a mixed effects ANOVA described in Section 5.2. Estimates 
of the adjusted mean differences (Test-Reference) and the corresponding 90% CIs 
will be obtained from the model. The adjusted mean differences and 90% CIs for the 
differences will be exponentiated to provide estimates of the ratio of adjusted 
geometric means (Test/Reference) and 90% CIs for the ratios.
In addition for Part 3 –

Plasma concentrations of PF-07202954 will be descriptively summarized and plotted by 
nominal PK sampling time and treatment;

The plasma PK parameters AUCinf, Cmax, AUClast, Tmax, Tlag, CL/F, Vz/F, and t½ will be 
summarized descriptively by treatment;

For AUCinf, Cmax, and AUClast, box and whisker plots will be presented by treatment and 
overlaid with geometric means.
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.
6.4. Subset Analyses
No subset analyses will be performed.
6.5. Baseline and Other Summaries and Analyses
Data will be reported separately for each part of this 3-part study in accordance with the 
sponsor’s reporting standards.
6.5.1. Baseline Summaries
Demographic data collected at screening will be reported as part of the standard baseline 
summary tables. A breakdown of demographic data will be provided for age, race, weight,
and body mass index. 
6.5.2. Study Conduct and Participant Disposition
Participant evaluation groups will show end of study participant disposition.  The 
presentation will include counts of participants analyzed for pharmacokinetics, and for 
safety.  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. 
6.5.4. Screening Data
These data will not be recorded in the study database, and therefore will not be listed.
6.6. Safety Summaries and Analyses
No formal analyses are planned for the standard safety data.
The safety endpoints detailed in Section 6.6.5 will be listed and summarized separately for 
each part of the study and in accordance with sponsor reporting standards based on the safety 
population (as defined in Section 4, Table 6), with more details provided below.
Medical history and physical 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 
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 
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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.
6.6.1. Treatment Emergent Adverse Events
Treatment emergent adverse events will be reported in accordance with the sponsor reporting 
standards.
6.6.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the sponsor 
reporting standards.  Baseline is as defined in Section 3.5.2.
6.6.3. Vital Signs
Parts 1 and 2 only 
Absolute values and changes from baseline in supine systolic and diastolic blood pressure 
and pulse rate will be summarized by treatment and time postdose, according to sponsor 
reporting standards.  Tables will be paged by parameter.  Baseline is as defined in Section 
3.5.3.
Mean changes from baseline for supine systolic and diastolic blood pressure and pulse rate 
will be plotted against time postdoses.  On each plot, there will be 1 line for each treatment, 
all treatments on the same plot including the placebo.  Corresponding individual plots of 
changes from baseline will also be produced for each treatment.
For supine systolic and diastolic blood pressure and pulse rate, the differences between each 
dose and placebo (dose – placebo) will be summarized (N, mean, 90% CI) and plotted 
(mean) for each dose and time postdose (including baseline).
Parts 1, 2 and 3 (if conducted)
Maximum absolute values and changes from baseline for vital signs will be summarized 
descriptively by treatment using categories as defined in Appendix 1.  Numbers and 
percentages of subjects meeting the categorical criteria will be provided.  All planned and 
unplanned postdose timepoints will be counted in these categorical summaries.  All values 
meeting the criteria of potential clinical concern will be listed.
Maximum increase or decrease in vital signs will also be summarized; all planned and 
unplanned postdose timepoints will be included in these summaries.
6.6.4. Electrocardiograms
Parts 1 and 2 only
Absolute values and changes from baseline for the ECG parameters QT interval, HR, QTcF 
interval, PR interval, and QRS complex will be summarized by treatment and time using 
sponsor reporting standards. Tables will be paged by parameter. Baseline is as defined in 
Section 3.5.4.


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Mean changes from baseline in QT, heart rate and QTcF will be plotted against time 
postdose.  On each plot there will be 1 line for each treatment, all treatments on the same plot 
including the placebo.  Corresponding individual plots of changes from baseline will also be 
produced for each treatment.
In addition for QTcF, heart rate and QT, the differences between each dose and placebo 
(dose – placebo) will be summarized and plotted (N, mean, 90% CI) for each dose and 
timepoint (including baseline). 
Changes from baseline in QTcF will be plotted separately against drug concentrations.  This 
will be a scatter plot for all observations where QTcF and drug concentration are recorded.  
Placebo data will also be included (with drug concentration set to zero).  Different symbols 
will be used for each treatment.  
In addition, an attempt may be made to explore and characterize the relationship between 
plasma concentration and QT interval length using a PK/PD modeling approach. If a PK/PD 
relationship is found, the impact of participant factors (covariates) on the relationship may be 
examined. However, this analysis will not be presented in the CSR.
Parts 1, 2 and 3 (if conducted)
ECG endpoints and changes from baseline (QTcF, PR and QRS) will also be summarized 
descriptively by treatment using categories as defined in Appendix 1 (for QTc these 
correspond to ICH E14).  Numbers and percentages of subjects meeting the categorical 
criteria will be provided.  All planned and unplanned postdose timepoints will be counted in 
these categorical summaries.  All values meeting the criteria of potential clinical concern will 
be listed.
When more than 1 ECG is collected at a nominal time after dose administration (for 
example, triplicate ECGs), the mean of the replicate measurements will be used to represent a 
single observation at that timepoint. If any of the 3 individual ECG tracings has a QTcF
value >500 msec, but the mean of the triplicates is not >500 msec, the data from the 
participant’s individual tracing will be described in a safety section of the CSR in order to 
place the >500 msec value in appropriate clinical context. However, values from individual 
tracings within triplicate measurements that are >500 msec will not be included in the 
categorical analysis unless the average from the triplicate measurements is also >500 msec.
The number of subjects with corrected (QTcF) and uncorrected single post-dose QT values 
500 msec will be listed.
QTcB, if collected, will be listed only and not summarized.
 
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7. INTERIM ANALYSES
7.1. Introduction
As guided by observed safety/tolerability, PK, 
 in 
Part 1 and Part 2 of this study, a formal interim analysis may be considered to evaluate 
potential revision to the currently proposed AUC24 PK stopping limit in Part 2 
(ie, AUC24=3,680 ng•h/mL).  This interim analysis will be used to evaluate whether repeated, 
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escalating doses of PF-07202954 yielding exposures greater than the currently planned PK 
stopping limit in Part 2 are attempted. If data are supportive, studying higher exposures will 
be contingent on a protocol amendment which will undergo the required regulatory and 
EC/IRB approvals. 
As this is a sponsor-open study, a limited number of the sponsor’s team members (excluding 
site staff) may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating dose-escalation decisions, facilitating PK/PD 
modeling, and/or supporting clinical development.
7.2. Interim Analyses and Summaries
If conducted, the objective of the interim analysis will be primarily to evaluate the PK 
stopping limit in Part 2 so that doses yielding higher exposures can be administered. To 
enable this PK, standard safety data and the biomarkers of kidney safety from all cohorts in 
Part 1 and Part 2 up to the date of data snapshot will be extracted and analyzed.  The 
unblinded data will be reviewed by the clnical, statistics and clinical pharmacology leads for 
this study and their leadership team. In addition, programming team will be unblinded. 
Participants, investigators and the site staff (except for the site pharmacist) will remain 
blinded. This is consistent with the sponsor-open design of this study and hence the standard 
methods of maintaining study blind will be implemented. The data to support interim 
analysis will be analyzed using the methods described in this SAP.
8. REFERENCES
1. CDISC Safety Rulebook - URL
2. McGill, R., John W. Tukey and W. A. Larsen., (1978), Variations of Box Plots. 
American Statistician 32:12-16
3.
Wu, J, Banerjee, A., Jin, B., Menon, S., Martin, S., and Heatherington, A., (2017), 
Clinical dose-response for a broad set of biological products: A model-based meta-
analysis, Statistical Methods in Medical Research, Vol. 7, No. 9, 2694-2721. 
4.
Thomas, N., and Roy, D. (2017). Analysis of clinical dose-response in small-molecule 
drug development: 2009-2014. Statistics in Biopharmaceutical Research, Vol. 9, No. 2, 
137-146. 
5.
Thomas, N., Sweeney, K., and Somayaji, V. (2014). Meta-analysis of clinical dose 
response in a large drug development portfolio, Statistics in Biopharmaceutical Research, 
Vol. 6, No.4, 302-317. 
6.
FDA Biomarker Qualification Decision and Executive Summary - URL


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1.
Appendices
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern
Bayesian analysis
Categories for QTcF
Categories for Maximum Post-dose QTcF (msec)
All participants
≤450
450 - ≤480
480 - ≤500
500
Categories for Maximum Increase from Baseline in QTcF (msec)
All participants
≤30
30 - ≤60
60
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
Standing pulse rate (bpm)
min. <40
max. >140
Measurements that fulfill these criteria are to be listed in the clinical study report.


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Appendix 2. List of Abbreviations
Abbreviation
Term
Abs
absolute
AE
adverse event
Aetau
Amount of unchanged drug recovered in urine during dosing interval
Aetau%
Percent of dose recovered in urine as unchanged drug over dosing 
interval
ANCOVA
analysis of covariance
ANOVA
Analysis of variance
AUC
area under the curve
AUCinf
area under the concentration-time curve from time 0 to infinity
AUClast
area under the concentration-time curve from time 0 to the time of 
the last quantifiable concentration
AUCtau
area under the concentration-time curve from time 0 to time τ (tau)
AUEC24
area under the effect curve over the time of 0-24 hours post dose 
BLQ
below the limit of quantitation
BP
blood pressure
CAPTM
Controlled attenuation parameter (trademarked by EchoSens®)
Cav
average concentrations
CDISC
Clinical Data Interchange Standards Consortium
CFB
Change from baseline
CI
confidence interval
Clast
Last quantifiable plasma concentration
CL/F
apparent clearance following oral administration
CLr
renal clearance
CL 
Systemic clearance
CM
Composite measure
Cmax
maximum observed concentration
Cmin
minimum observed concentration
CRF
case report form
CRU
clinical research unit
CSR
clinical study report
%CV
percent coefficient of variation
CYP
cytochrome P450
E0
Efficacy at 0 dose level; also treated as placebo effect
EC
ethics committee
ECG
electrocardiogram
ED50
effective dose for 50% of the maximal efficacy
Emax
maximum response achievable
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Abbreviation
Term
FDA
Food and Drug Administration (United States)
FPG
Fasting plasma glucose
FPI
Fasting plasma insulin
GCP
Good Clinical Practice
GM
Geometric mean
GMC
geometric mean concentration
GMR
Geometric mean ratio
HDL-C
high-density lipoprotein cholesterol
HR
Heart Rate
IA
Interim Analysis
ICH
International Council for Harmonisation
Kel
terminal phase rate constant calculated by a linear regression of the 
log-linear concentration-time curve
LDL-C
low-density lipoprotein cholesterol
LLQ
lower limit of quantitation
LS
least-squares
LSM
least-squares mean
MAR
Missing at random
MATE
multidrug and toxin extrusion
max
maximum
min
minimum
MMRM
mixed-effects model with repeated measures
N/A
not applicable
NC
Not calculated
ND
Not done
NS
No sample
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PO
per oral
PP
per-protocol
PR interval
interval between the start of the electrocardiogram P wave and start 
of QRS complex, corresponding to time between onset of atrial 
depolarization and onset of ventricular depolarization
PT
preferred term
PTR
peak-to-trough ratio
QRS
combination of 3 graphical deflections seen on a typical 
electrocardiogram
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Abbreviation
Term
QT
time from electrocardiogram Q wave to end of T wave 
corresponding to electrical systole
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac
observed accumulation ratio
RR
Response ratio
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SOP
standard operating procedure
t½
terminal elimination half-life 
TG
triglyceride(s)
Tlag
lag time 
Tmax
time to reach maximum observed concentration
ULN
upper limit of normal
VCTETM
Vibration-controlled transient elastography (trademarked by 
EchoSens®) 
VLDL-C
very low density lipoprotein cholesterol
Vss
steady-state volume of distribution following IV infusion
Vz/F
apparent volume of distribution following oral administration
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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