Clinical trial NCT06003777
Conditions: Healthy Participants
Sponsor: Pfizer
Start date: 2023-08-30; Completion date: 2024-02-20
Enrollment: 26 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purposes of this study are:

* To see how the new medicine (PF-06954522) under study behave. And if there are any important side effects. A side effect is a reaction (expected or unexpected) to a medicine or treatment you take. The study will see how people feel after taking single increasing amount of the medicine by mouth.
* To measure the amount of study medicine in your blood after the medicine is taken by mouth.

This study is seeking for participants who:

* are females of 18 to 65 years old and are not able to give birth to a child.
* are males of 18 to 65 years old.
* have body mass index of 16 to 31 kilograms per meter squared.
* have a total body weight of more than 50 kilograms (110 pounds).

Participants will be chosen by chance, like drawing names out of a hat to receive either:

* study medicine (PF-06954522)
* or placebo (a pill that has no medicine in it).

Participants may receive up to 4 amounts of study medicine and up to 2 amounts of placebo. The time frame of the study is approximately up to 36 days for each group and participants will stay at CRU for 20 days.

Detailed description:

Arms: arm 1: Single dose administration of PF-06954522 and placebo. Participants will receive up to 5 dose levels of PF-06954522 and up to 2 dose levels of matching placebo. arm 2: Single dose administration of PF-06954522 and placebo. Participants will receive up to 4 dose levels of PF-06954522 and up to 2 dose levels of matching placebo. arm 3: Single dose administration of PF-06954522 and placebo. Participants will receive up to 2 dose levels of PF-06954522 and up to 1 dose level of matching placebo.
Interventions: intervention 1: PF-06954522 intervention 2: Placebo
Intervention descriptions: intervention 1: PF-06954522 will be administered as oral suspensions as escalating single doses to be determined. intervention 2: Placebo will be administered as oral suspensions as escalating single doses to be determined.

Protocol documents:
Prot_000.pdf: 
PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 1
Title Page
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-
CONTROLLED, CROSSOVER, FIRST-IN-HUMAN STUDY TO ASSESS THE 
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE 
ASCENDING ORAL DOSES OF PF-06954522 IN HEALTHY ADULT 
PARTICIPANTS
Study Intervention Number:
PF-06954522
Study Intervention Name:
NA
US IND Number:
167845
EudraCT/EU CT Number:
NA
ClinicalTrials.gov ID:  
NA
Pediatric Investigational Plan Number:
NA
Protocol Number:
C4001001
Phase:
1
Sponsor Legal Address:
Pfizer Inc.
66 Hudson Boulevard East
New York, NY 10001
Brief Title: A Study to Learn How Different Amounts of the Study Medicine called 
PF-06954522 are Tolerated and act in the Body in Healthy Adults
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 2
Document History
Document
Version Date
Original protocol
17 July 2023
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 3
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
LIST OF FIGURES ...................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................14
1.3. Schedule of Activities .............................................................................................16
2. INTRODUCTION ...............................................................................................................21
2.1. Study Rationale .......................................................................................................21
2.2. Background .............................................................................................................21
2.2.1. Nonclinical Pharmacology..........................................................................22
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................22
2.2.3. Biopharmaceutics .......................................................................................23
2.2.4. Nonclinical Safety ......................................................................................23
2.3. Benefit/Risk Assessment.........................................................................................24
2.3.1. Risk Assessment.........................................................................................26
2.3.2. Benefit Assessment.....................................................................................28
2.3.3. Overall Benefit/Risk Conclusion................................................................28
3. OBJECTIVES AND ENDPOINTS.....................................................................................28
4. STUDY DESIGN.................................................................................................................28
4.1. Overall Design.........................................................................................................28
4.2. Scientific Rationale for Study Design.....................................................................30
4.2.1. Choice of Contraception/Barrier Requirements .........................................31
4.3. Justification for Dose ..............................................................................................31
4.3.1. Human PK Prediction.................................................................................31
4.3.2. Predicted Human Efficacious Dose and Concentration..............................32
4.3.3. Human Exposure Stopping Limits..............................................................32
4.3.4. Rationale for Dose Selection ......................................................................32
4.4. End of Study Definition ..........................................................................................34
5. STUDY POPULATION......................................................................................................34
5.1. Inclusion Criteria.....................................................................................................34
5.2. Exclusion Criteria....................................................................................................35
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 4
5.3. Lifestyle Considerations..........................................................................................37
5.3.1. Contraception..............................................................................................37
5.3.2. Meals and Dietary Restrictions...................................................................38
5.3.3. Caffeine, Alcohol, and Tobacco .................................................................39
5.3.4. Activity .......................................................................................................39
5.4. Screen Failures ........................................................................................................40
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................40
6.1. Study Intervention(s) Administered........................................................................40
6.1.1. Administration............................................................................................41
6.2. Preparation, Handling, Storage, and Accountability...............................................42
6.2.1. Preparation and Dispensing........................................................................43
6.3. Assignment to Study Intervention...........................................................................43
6.4. Blinding...................................................................................................................43
6.4.1. Blinding of Participants..............................................................................43
6.4.2. Blinding of Site Personnel..........................................................................44
6.4.3. Blinding of the Sponsor..............................................................................44
6.4.4. Sensitive Clinical Data ...............................................................................44
6.4.5. Breaking the Blind......................................................................................44
6.5. Study Intervention Compliance...............................................................................45
6.6. Dose Modification...................................................................................................45
6.6.1. Dose Escalation and Stopping Rules..........................................................46
6.7. Continued Access to Study Intervention After the End of the Study......................47
6.8. Treatment of Overdose............................................................................................47
6.9. Prior and Concomitant Therapy ..............................................................................47
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................48
7.1. Discontinuation of Study Intervention ....................................................................48
7.1.1. Potential Cases of Acute Kidney Injury .....................................................48
7.1.2. Liver Injury.................................................................................................50
7.1.3. ECG Changes..............................................................................................50
7.1.4. COVID-19 ..................................................................................................50
7.2. Participant Discontinuation/Withdrawal From the Study.......................................51
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 5
7.2.1. Withdrawal of Consent...............................................................................51
7.3. Lost to Follow-Up ...................................................................................................52
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................52
8.1. Administrative and Baseline Procedures.................................................................52
8.2. Efficacy Assessments..............................................................................................53
8.3. Safety Assessments .................................................................................................53
8.3.1. Physical Examinations................................................................................54
8.3.2. Vital Signs ..................................................................................................54
8.3.2.1. Blood Pressure and Pulse Rate..................................................54
8.3.2.2. Respiratory Rate........................................................................55
8.3.2.3. Body Temperature.....................................................................55
8.3.3. Electrocardiograms.....................................................................................55
8.3.3.1. Continuous Cardiac Monitoring by Telemetry .........................56
8.3.4. Clinical Safety Laboratory Assessments ....................................................56
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................57
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......57
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................58
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................58
8.4.2. Method of Detecting AEs and SAEs ..........................................................58
8.4.3. Follow-up of AEs and SAEs.......................................................................59
8.4.4. Regulatory Reporting Requirements for SAEs...........................................59
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................59
8.4.5.1. Exposure During Pregnancy......................................................59
8.4.5.2. Exposure During Breastfeeding ................................................61
8.4.5.3. Occupational Exposure .............................................................62
8.4.6. Cardiovascular and Death Events...............................................................62
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................62
8.4.8. Adverse Events of Special Interest.............................................................62
8.4.8.1. Lack of Efficacy........................................................................62
8.4.9. Medical Device Deficiencies......................................................................62
8.4.10. Medication Errors.....................................................................................62
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6
8. 5. P har mac o ki netics .................................................................................................... 6 3
8. 6. Ge netics ................................................................................................................... 6 4
8. 6. 1. S pecifie d Ge netics ...................................................................................... 6 4
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics ................................................... 6 4
8. 7. Bi o mar kers .............................................................................................................. 6 4
8. 7. 1. Plas ma f or Meas ure me nt of 
...............................................................6 4
8. 7. 2. Retai ne d Researc h Sa m ples f or Bi o mar kers ............................................... 6 5
8. 8. I m m u n o ge nicit y Assess me nts ................................................................................. 6 6
8. 9. Healt h Ec o n o m ics ................................................................................................... 6 6
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 6 6
9. 1. Statistical H y p ot hesis ..............................................................................................6 6
9. 2. A nal y sis Sets ........................................................................................................... 6 6
9. 3. Statistical A nal y ses ................................................................................................. 6 7
9. 3. 1. Safet y A nal ys es .......................................................................................... 6 7
9. 3. 1. 1. Electr ocar di o gra m A nal y ses...................................................... 6 7
9. 3. 2. P K A nal y sis ................................................................................................ 6 8
9. 3. 2. 1. Deri vati o n of P F -0 6 9 5 4 5 2 2 P K Para meters .............................. 6 8
9. 3. 2. 2. Statistical Met h o ds f or P K Data ................................................ 6 9
9. 3. 3. Tertiar y / E x pl orat or y E n d p oi nt(s) A nalys is ................................................ 6 9
9. 3. 4. Ot her A nal ys es ............................................................................................ 6 9
9. 4. Interi m A nal ys es ..................................................................................................... 7 0
9. 5. Sa m ple Size Deter mi nati o n ..................................................................................... 7 0
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S .......................................................................................................... 7 1
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns............... 7 1
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns .................................................... 7 1
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P ......................................................................... 7 1
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................7 2
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................7 2
1 0. 1. 3. 1. Electr o nic C o nse nt .................................................................. 7 3
1 0. 1. 4. Data Pr otecti o n ......................................................................................... 7 3
1 0. 1. 5. C o m mittees Str uct ure ............................................................................... 7 3
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 7
10.1.5.1. Data Monitoring Committee ...................................................73
10.1.6. Dissemination of Clinical Study Data ......................................................73
10.1.7. Data Quality Assurance ............................................................................75
10.1.8. Source Documents....................................................................................76
10.1.9. Use of Medical Records............................................................................76
10.1.10. Study and Site Start and Closure ............................................................77
10.1.11. Publication Policy...................................................................................77
10.1.12. Sponsor’s Medically Qualified Individual..............................................78
10.2. Appendix 2: Clinical Laboratory Tests .................................................................79
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................81
10.3.1. Definition of AE .......................................................................................81
10.3.2. Definition of an SAE ................................................................................82
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................83
10.3.4. Reporting of SAEs....................................................................................87
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................88
10.4.1. Male Participant Reproductive Inclusion Criteria....................................88
10.4.2. Female Participant Reproductive Inclusion Criteria.................................88
10.4.3. Woman of Childbearing Potential ............................................................89
10.4.4. Contraception Methods.............................................................................90
10.5. Appendix 5: Genetics............................................................................................92
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......93
10.7. Appendix 7: Kidney Safety: Monitoring Guidelines ............................................95
10.7.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury..............................................................................95
10.7.2. Age-Specific Kidney Function Calculation Recommendations...............95
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations...........................................................................................95
10.7.3. Kidney Function Calculation Tools..........................................................95
10.7.4. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities...................................................................................................96
10.8. Appendix 8: ECG Findings of Potential Clinical Concern ...................................97
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 8
10.9. Appendix 9: Prohibited Concomitant Medications That May Result in DDI.......99
10.10. Appendix 10: Abbreviations .............................................................................101
11. REFERENCES ................................................................................................................106
LIST OF TABLES
Table 1.
Study Schedule of Assessments................................................................16
Table 2.
Study Schedule of Assessments for PK, Vitals, and ECGs on Day 1 
of Each Period...........................................................................................20
Table 3.
Predicted Human Exposure and Safety Margins Following 
Administration of Single Oral Doses of PF-06954522.............................33
Table 4.
Plasma PF-06954522 PK Parameters .......................................................68
Table 5.
Protocol -Required Laboratory Assessments............................................79
Table 6.
Protocol-Required Laboratory Assessments – Reflex Testing.................80
LIST OF FIGURES
Figure 1.
Study Design Schematic: Sequential, Placebo-Controlled, 5-Period, 
Crossover Design......................................................................................15
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 9
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: 
A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Crossover,
First-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single 
Ascending Oral Doses of PF-06954522 in Healthy Adult Participants
Brief Title:
A Study to Learn How Different Amounts of the Study Medicine Called PF-06954522 are 
Tolerated and Act in the Body in Healthy Adults
Regulatory Agency Identification Number(s):
US IND Number:
167845
EudraCT/EU CT Number:
NA
ClinicalTrials.gov ID:  
NA
Pediatric Investigational Plan Number:
NA
Protocol Number:
C4001001
Phase:
1
Rationale:
PF-06954522 is an orally administered small molecule glucagon-like peptide-1 receptor 
(GLP-1R) agonist that is being developed as an adjunct to diet and exercise for the treatment 
of type 2 diabetes mellitus (T2DM). The purpose of this study is to evaluate the safety, 
tolerability, and pharmacokinetics (PK) of single ascending oral doses of PF-06954522 in 
healthy adult participants. This study is the first time that PF-06954522 is administered to 
humans. The safety, tolerability, and PK results obtained from this study will inform future 
clinical development of PF-06954522.
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 10
Objectives and Endpoints:
Objectives
Endpoints
Primary: 
Primary: 
! To evaluate the safety and tolerability of single 
oral doses of PF-06954522 administered to 
healthy adult participants.
! Assessment of AEs, safety laboratory tests, vital 
signs (blood pressure, pulse rate, respiratory rate
and temperature), cardiac telemetry and standard 
12-lead ECGs, and PE.
Secondary: 
Secondary: 
! To characterize the plasma PK of PF-06954522 
following single oral doses of PF-06954522 
administered to healthy adult participants.
! PF-06954522 PK parameters: AUClast, Cmax, Tmax, 
and if data permit AUCinf and t½.
Abbreviations: AE = adverse event; AUCinf = area under the plasma concentration-time curve from time 0 
extrapolated to infinite time; AUClast = area under the plasma concentration-time curve from time 0 to the 
time of the last quantifiable concentration; Cmax = maximum plasma concentration; 
ECG = electrocardiogram; PE = physical examination; PK = pharmacokinetic(s); t½. = terminal half-life; 
Tmax = time for Cmax.
Overall Design: This study is a randomized, double-blinded (investigator- and 
participant-blinded), sponsor-open, first in human (FIH), single-ascending oral dose, 5-period 
crossover, placebo substitution design in 1 cohort of healthy adult participants. An optional 
cohort, enrolling healthy adult participants in up to 4 crossover periods, may be included to 
permit assessment of any of the following: repeat of a previously administered dose level; 
studying additional dose levels as dictated by the evaluated safety, tolerability, or PK of 
earlier dose levels; or any other assessment needed to meet the objectives of this study. A 
second optional cohort enrolling Japanese participants to receive PF-06954522 or placebo in 
up to 3 periods, may also be included.
Number of Participants: Approximately 24 healthy adult participants will be enrolled in the 
study. This includes up to approximately 10 healthy participants for Cohort 1, up to 
approximately 8 healthy participants for optional Cohort 2 and up to approximately 6 healthy 
Japanese participants for the optional Cohort 3. The actual number of Japanese participants 
may be adjusted based on emerging data or operational factors with a maximum sample size 
of up to 8 participants (6 receiving PF-06954522 and 2 receiving placebo in each period).
Note: "Enrolled" means a participant’s, or their legally authorized representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process and randomization to study intervention.
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 1
St u d y P o p ul ati o n :
K e y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
Part ici pa nts m ust meet t he f oll o wi n g ke y i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
1.
Male a n d fe male partici pa nts of n o n -c hil d beari n g p ote ntial a ge d 1 8 t o 6 5 years , i ncl usi ve,
at scree ni n g w h o are o vertl y  healt h y as deter mi ne d b y me dical eval uati o n i ncl u di n g 
me dical hist or y , p h ysical e xa mi nati o n, la b orat or y tests, a n d car diac m o nit ori n g. 
2.
B MI of 1 6 t o 3 0. 5 k g/ m 2; a n d a t otal b o dy wei g ht > 5 0 k g ( 1 1 0 l b).
N ote : partici pa nts e nr olli n g as Ja pa nese m ust ha ve 4 bi ol o gical Ja pa nese gra n d pare nts w h o 
were b or n i n Ja pa n. A l o wer e ntr y wei g ht of 4 5 k g ma y  be c o nsi dere d if t he t otal bl o o d 
v ol u me c ollecti o n f or t h is c o h ort d oes N O T e xcee d 3 6 0 m L  o ver a n 8-wee k peri o d.
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, p ul m o nar y, 
gastr oi ntesti nal, car di o vasc ular, he patic, ps y c hiatric, ne ur ol o gical, or aller gic disease 
(i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as ym p t o matic, seas o nal aller gies at t he 
ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, c h olec ystect o my). 

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V, H Bs A g , 
H Bc A b, or H C V A b. Hist or y  of he patitis B vacci nati o n wit h a n is olate d p ositi ve 
H Bs A b res ult is all o we d.
2.
Pers o nal or fa mil y hist or y of me d ullar y  t h yr oi d carci n o ma ( M T C) or m ulti ple e n d ocri ne 
ne o plasia s y n dr o me t y pe 2 ( M E N 2), or partici pa nts wit h s us pecte d M T C per t he 
i n vesti gat or’s j u dge me nt.
3.
A n y  me dical or psyc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/ be ha vi or or la b orat or y a b n or malit y or ot her c o n diti o ns t hat ma y i ncrease 
t he ris k of st u d y partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, make t he partici pa nt 
i na p pr o priate f or t he st u d y. 
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts wit hi n 
7 da y s or 5 half-li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y i nter ve nti o n, 
wit h t he e xce pti o n of 
 
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 2
 w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o t he first d ose of 
st u d y i nter ve nti o n. 
5.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 3 0 da y s 
( or as deter mi ne d by t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first d ose of 
st u d y i nter ve nti o n use d i n t his st u d y ( w hic he ver is l o n ger). Partici pati o n i n st u dies of 
ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a n y  ti me d uri n g t heir partici pati o n i n 
t his st u d y.
6.
A p ositi ve uri ne dr u g test at Scree ni n g or a d missi o n.
7.
Scree ni n g s u pi ne bl o o d press ure ( B P) ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g ( diast olic) 
f or partici pa nts < 6 0 years; a n d ≥1 5 0/ 9 0 m m/ H g f or partici pa nts ≥6 0 ye ars ol d, f oll o wi n g 
at least 5 mi n utes of s u pi ne rest. If s ys t olic B P is ≥1 4 0 or 1 5 0 m m H g ( base d o n a ge) or 
diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti m es a n d t he a vera ge of t he 
3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s eli gi bilit y .
8.
Re nal i m pair me nt as defi ne d b y a n esti mate d gl o mer ular filtrati o n rate (e G F R) of 
< 7 5 m L / mi n/ 1. 7 3 m². Base d u p o n partici pa nt a ge at scree ni n g, e G F R is calc ulate d usi n g 
t he rec o m me n de d C hr o nic K i d ne y Disease E pi de mi ol o g y C olla b orati o n ( C K D-E PI) 
e q uati o ns t o deter mi ne eli gi bilit y (Screat -base d f or m ula ) a n d t o pr o vi de a baseli ne 
(Screat -S c y s c o m bi ne d f or m ula) t o q ua ntif y s u bse q ue nt ki d ne y safety e ve nts. F or 
eli gi bilit y assess me nt base d u p o n esti mate d re nal f u ncti o n, t he hi g her of t he scree ni n g 
a n d baseli ne e G F R val ues ma y  be use d.
9.
Sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nically rele va nt a b n or malities t hat ma y affect 
partici pa nt safet y  or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms, c o m plete L B B B, 
si g ns of a n ac ute or i n deter mi nate a ge m yocar dial i nfarcti o n, S T -T i nter val c ha n ges 
s u g gesti ve of m yocar dial isc he mia, sec o n d- or t hir d - de gree atri o ve ntric ular ( A V) bl oc k, 
or seri o us bra d ya rr hyt h mias or tac h y arr h yt h mias). If Q Tc F e xcee ds 4 5 0 ms, or Q R S 
e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 3 Q Tc F or 
Q R S val ues use d t o deter mi ne t he partici pa nt’s eli gi bilit y . C o m p uter -i nter prete d E C Gs 
s h o ul d be o verrea d by a p h ysicia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a 
partici pa nt.
1 0. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
scree ni n g, as assesse d by t he st u d y  s pecific la b orat or y a n d c o nfir me d by a si n gle re peat 
test, if dee me d necessar y: 

Ala ni ne a mi n otra nsferase (A L T ), as partate a mi n otra nsferase (A S T ), or b ilir u bi n 
≥1. 0 5 × u p per li mit of n or mal (U L N ). Partici pa nts wit h a n ele vate d t otal bilir u bi n 
c o nsiste nt wit h Gil bert’s Disease m a y ha ve a direct bilir u bi n meas ure d a n d w o ul d be 
eli gi ble f or t his st u d y pr o vi de d t he direct bilir u bi n le vel is ≤U L N ;

T S H > U L N; 

H b A 1c ≥6. 5 %;
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 3

He mat uria as defi ne d b y ≥1 + he me o n uri ne d i pstic k;

Al b u mi n uria as defi ne d b y uri ne al b u mi n/creati n i ne rati o ( U A C R) > 3 0 m g/ g.
1 1. Hist or y  of alc o h ol a b use or bi n ge dri n ki n g a n d/ or a n y ot her illicit dr u g use or de pe n de nce 
wit hi n 6 m o nt hs of scree ni n g. Bi n ge dri n ki n g is defi ne d as a patter n of 5 ( male) a n d 
4 (fe male) or m ore alc o h olic dri n ks i n a b o ut 2 h o urs. As a ge neral r ule, alc o h ol i nta ke 
s h o ul d n ot e xcee d 1 4 u nits per wee k ( 1 u nit = 8 o u nces ( 2 4 0 m L ) beer, 1 o u nce ( 3 0 m L ) 
of 4 0 % s pirit, or 3 o u nces ( 9 0 m L ) of wi ne).
1 2. Use of t o bacc o or nic oti ne- c o ntaini n g pr o d ucts i n e xcess of t he e q ui vale nt of 
5 ci garettes/ da y or 2 c he ws of t o bacc o/ da y.
1 3. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers. 
St u d y Ar ms a n d D ur ati o n: T he t otal d urati o n of partici pati o n fr o m t he scree ni n g visit t o t he 
tele p h o ne f oll o w-u p c o ntact will be a p pr o xi matel y 1 5 wee ks f or ea c h partici pa nt.
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 6 9 5 4 5 2 2
Place b o
Use
E x peri me ntal
P lace b o
I M P or NI M P/ A x M P
I M P
I M P
D ose F or m ul ati o n
B ul k p o w d er f or e xte m p ora neo us
pre parati o n of oral s us pe nsi o n s
B ul k p o w d er f or e xte m p ora neo us
pre parati o n of oral s us pe nsi o n s
U nit D ose Stre n gt h(s)
m g
0 m g
R o ute of A d mi nistr ati o n
Oral
Oral
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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Page 14
Study Arm(s)
Arm Title
Cohort 1
Cohort 2 (Optional)
Cohort 3 (Optional)
Arm Description
Participants may receive up 
to 5 dose levels of 
PF-06954522 and matching 
placebo. Doses will be 
administered as oral 
suspensions as escalating 
single doses to be 
determined.
Participants may receive up 
to 4 dose levels of 
PF-06954522 and matching 
placebo. Doses will be 
administered as oral 
suspensions as escalating 
single doses to be 
determined.
Participants may receive up 
to 3 dose levels of 
PF-06954522 and matching 
placebo. Doses will be 
administered as oral
suspensions as escalating 
single doses to be 
determined.
Assessment of the safety, tolerability, and PK after each single dose level will be conducted 
before escalating to the next dose level. The dose/exposure-escalation increments are planned 
to be up to approximate semi-logarithmic increases in exposure from the previous highest 
dose level that has been evaluated. The actual dose levels, target exposures, and/or dose level 
increments may be adjusted during the study based on emerging human safety, tolerability, 
and PK data, but projected exposures will not exceed the predefined human exposure limits.
Statistical Methods: The sample size has been chosen based on the need to minimize first 
exposure to humans of a new chemical entity and the requirement to conduct adequate 
safety, tolerability, and PK assessments at each dose level. All safety analyses will be 
performed on the safety analysis set, which is defined as all participants randomly assigned 
to study intervention and who take at least 1 dose of study intervention. Participants will be 
analyzed according to the study intervention they actually received. Safety data will be 
presented in tabular and/or graphical format and summarized descriptively, where 
appropriate. The plasma PK parameters for PF-06954522 following oral dose administration 
will be derived from the plasma concentration‑time profiles. Plasma PK parameters and 
concentrations of PF-06954522 will be descriptively summarized by dose (and fasting 
condition, and ethnicity, if appropriate) and nominal time, as appropriate.
Ethical Considerations:
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 
be expected to commit time and may experience some discomfort while undergoing study 
procedures. However, they will receive close monitoring of their safety via safety monitoring 
procedures (eg, physical examinations, 12-lead ECGs, vital signs) as outlined in this 
protocol. Based on the totality of available nonclinical data and taking into account the 
measures to minimize risk to study participants, the overall benefit/risk profile supports 
clinical testing of PF-06954522 in this study as part of the clinical development of an adjunct 
to diet and exercise for the treatment type 2 diabetes mellitus (T2DM).
1.2. Schema
A sample study design schematic is presented in Figure 1. It should be noted that this is for 
illustrative purposes, only. 
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PF-06954522
Protocol C4001001
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2. INTRODUCTION
GLP-1 is a neuroendocrine hormone that is predominantly released from the small intestine 
in response to food intake.[1] Activation of the GLP-1 receptor stimulates insulin release, 
inhibits glucagon secretion in a glucose-dependent manner, and delays gastric emptying.[2,3]
In addition, GLP-1 has been shown to increase satiety and suppress food intake.[4]
PF-06954522 is an orally administered small molecule GLP-1 receptor agonist that is 
currently being developed as an adjunct to diet and exercise to improve glycemic control in 
adults with T2DM.
2.1. Study Rationale 
The purpose of this study is to evaluate the safety, tolerability and PK of single ascending 
oral doses of PF-06954522 in healthy adult participants. This study is the first time that 
PF-06954522 will be administered to humans. The safety, tolerability and PK results 
obtained from this study will inform future clinical development of PF-06954522.
2.2. Background 
Diabetes is estimated to affect more than 500 million adults (aged 20-79) worldwide.[5] The 
increase in the global prevalence of T2DM is largely attributed to rising rates of excess body 
weight and obesity.[6] T2DM is characterized by insulin resistance, a disorder in which cells 
do not respond effectively to insulin, resulting in higher blood glucose levels. Elevated blood 
glucose levels and increasing severity of insulin resistance result in the need for more insulin 
over time, eventually resulting in progressive pancreatic #-cell failure.[7] Patients with 
poorly controlled T2DM have an increased risk of developing complications associated with 
both microvascular and macrovascular disease, including nephropathy, neuropathy, 
retinopathy, and cardiovascular disease; and are at 2 to 4 times increased risk of mortality 
when compared with adults who do not have diabetes.[8] While existing pharmacological 
options for the treatment of diabetes may provide satisfactory glycemic control for some 
patients, there remain a large number of patients who do not achieve target HbA1c levels, 
suggesting a need for additional therapeutic options which minimize patient burden such as 
oral therapies. 
Currently available GLP-1R agonists have demonstrated robust efficacy for glycemic
control, weight loss, and CV safety, with several agents having shown a benefit in CV 
outcomes.[9] Most available GLP-1R agonist treatment options are injected once weekly 
subcutaneously.[10],[11] Injectable therapies are often underutilized due to patient hesitancy, 
whereas oral options are preferred by many patients. Only one GLP-1R agonist (Rybelsus∃; 
oral semaglutide) is currently commercially available for oral administration. However, oral 
semaglutide has strict administration requirements (food and water restrictions) and has 
limitations due to its low bioavailability[12], making it less convenient than an agent without 
such restrictions. A novel oral small molecule GLP-1R agonist that may further improve 
glycemic control, reduce HbA1c levels, and decrease food intake and body weight compared 
to existing oral GLP-1R agonist, without any administration restrictions, is expected to be a 
preferred therapeutic option for patients with T2DM and their physicians. Another small 
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
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treatment of patients with T2DM. As of the date of this protocol, no specific human risks 
have been identified; postulated risks based on nonclinical studies with PF-06954522 and 
marketed GLP-1R agonists are summarized in Section 2.3.1. The clinical impact of any
potential risks will be minimized through the proposed cautious dose escalation process 
wherein higher doses of PF-06954522 will be administered only after lower doses have been 
found to be well tolerated with an acceptable safety profile (Section 4.2 and Section 4.3). In
addition, this study will employ stopping rules for dose escalation (Section 6.6.1) and 
includes standard, intensive, inpatient monitoring of the participants following administration 
of single, oral doses of the study intervention as outlined in the SoA.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-06954522 may be found in the IB, which is the SRSD for this study.
Refer to the Study Intervention(s) table in Section 6.1 for a complete description of SRSDs.
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s) PF-06954522
Gastrointestinal adverse reactions
The potential risks are based on product labeling for 
injectable GLP-1R agonists (ie, liraglutide, exenatide, 
semaglutide and dulaglutide).
Study includes inpatient monitoring of the 
participants following administration of a 
single dose of the study intervention.
Participants are monitored to prevent 
potential sequelae of any severe 
gastrointestinal reactions, eg, dehydration.
Hypoglycemia
Clinical trials with injectable GLP-1R agonists have not
demonstrated an increased risk for hypoglycemia. However, 
when administered in combination with anti-diabetic agents 
that are known to have an increased risk of hypoglycemia 
(such as insulin or sulfonylureas), an increased risk for 
hypoglycemia was observed.
The participants enrolled will not have 
diabetes and will not be receiving 
anti-diabetic agents. 
Study includes inpatient monitoring of the 
participants following administration of a 
single dose of the study intervention.
Increased heart rate and decreased PR interval
Based on the product labeling for the injectable GLP-1R 
agonist liraglutide for obesity, mean increases in resting 
heart rate ranged 2 to 3 bpm in clinical trials, with some 
participants experiencing greater increases in resting heart 
rate, up to 10-20 bpm. Increased heart rate and decreased 
PR interval was observed in a single-dose NHP study of PF-
06954522.
Study includes inpatient monitoring of the 
participants through periodic vital sign 
assessment, ECGs and telemetry following 
administration of a single dose of the study 
intervention.
Other potential risks associated with long-term 
dosing of marketed GLP-1R agonists include 
thyroid C-cell tumors, pancreatitis, impairment 
in renal function, diabetic retinopathy 
complications, suicidal ideation/behavior and 
acute gallbladder disease.
These potential risks are based on product labeling for 
injectable GLP-1R agonists (ie, liraglutide, dulaglutide, 
exenatide and semaglutide).
This is a single dose study in healthy 
participants. 
Participants with a personal or family 
history of MTC or MEN2; with acute 
pancreatitis or a history of chronic 
pancreatitis are not eligible for study entry.
Study includes inpatient monitoring and 
safety laboratory surveillance (eg,
calcitonin, amylase, lipase, eGFR) of the 
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s) PF-06954522
participants following administration of a 
dose of the study intervention.
Increased transaminases (eg, ALT & AST) 
Elevated ALT and AST were observed in a subset of 
participants in the lotiglipron clinical studies following 
multiple dose administration. 
Study includes inpatient monitoring and 
safety laboratory surveillance (eg, LFTs) of 
the participants following administration of 
a dose of the study intervention.
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 8
2. 3. 2. Be nefit Assess me nt
T he partici pa nts i n t his st u d y are n ot e x pecte d t o o btai n a n y s pecific be nefit be yo n d 
c o ntri b uti n g t o t he pr ocess of de vel o pi n g ne w t hera pies i n a n area of u n met nee d.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
Base d o n all a vaila ble data o n P F - 0 6 9 5 4 5 2 2, as well as data a vaila ble f or ot her GL P - 1-R 
a g o nists a n d c o nsi deri n g t he meas ures t o mi ni mize ris k t o st u d y partici pa nts , t he p ote ntial 
ris ks i de ntifie d i n ass ociati o n wit h P F -0 6 9 5 4 5 2 2 are j ustifie d b y t he a ntici pate d be nefits t hat 
ma y  be aff or de d t o partici pa nts wit h T 2 D M .
3. O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
Pri m ar y : 
Pri m ar y : 

T o e val uate t he safet y a n d t olera bilit y of si n gle oral 
d oses of P F - 0 6 9 5 4 5 2 2, a d mi nistere d t o healt h y a d ult 
partici pa nts.

Assess me nt of A Es, safet y la b orat or y tests, vital si g ns 
( bl o o d press ure, p ulse rate , te m perat ure), car diac 
tele metr y a n d sta n dar d 1 2-lea d E C Gs, a n d P E.
Sec o n d ar y: 
Sec o n d ar y: 

T o c haracterize plas ma P K of P F -0 6 9 5 4 5 2 2 f oll o wi n g 
si n gle oral d oses of P F-0 6 9 5 4 5 2 2 a d mi nistere d t o 
healt h y a d ult partici pa nts.

P F - 0 6 9 5 4 5 2 2 P K para meters: A U C last, Cma x, Tma x , a n d if 
data per mit , A U C i nf a n d t½ .
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y: 

T o f urt her c haracterize plas ma P K of P F - 0 6 9 5 4 5 2 2 
f oll o wi n g si n gle oral d oses of P F-0 6 9 5 4 5 2 2 
a d mi nistere d t o healt h y a d ult partici pa nts.

O pti o nal: t o c haracterize t he effect of f o o d ( hi g h -fat
brea kfast) o n t he plas ma P K of P F - 0 6 9 5 4 5 2 2 
f oll o wi n g si n gle oral d oses of P F -0 6 9 5 4 5 2 2 i n 
healt h y a d ult partici pa nts. 

O pti o nal: t o e x pl ore t he safet y, t olera bilit y, a n d 
plas ma P K of P F -0 6 9 5 4 5 2 2 i n healt h y a d ult Ja pa nese 
partici pa nts.

A d diti o nal P F -0 6 9 5 4 5 2 2 P K para meters: A U C last( d n), 
C ma x( d n), a n d if data per mit, A U C i nf( d n), C L/ F , a n d 
V z/ F.

P F - 0 6 9 5 4 5 2 2 P K para meters after a hi g h-fat meal: 
A U C last, Cma x, T ma x a n d if data per mit, A U C i nf, C L/ F, 
V z/ F a n d t ½ .

A ssess me nt of A Es, safet y la b orat or y tests, vital si g ns 
( bl o o d press ure, p ulse rate a n d te m perat ure), sta n dar d 
1 2 -lea d E C Gs a n d t he f oll o wi n g P F-0 6 9 5 4 5 2 2 P K 
para meters i n Ja pa nese partici pa nts : A U Clast, Cma x, 
T ma x , a n d if data per mit , A U C i nf, C L/ F , Vz/ F a n d t ½ .
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his FI H st u d y has a d o u ble- bli n de d (i n vesti gat or- a n d partici pa nt bli n de d), s p o ns or-o pe n, 
ra n d o mize d, si n gle-asce n di n g oral d ose, u p t o 5 peri o d cr oss o ver, place b o s u bstit uti o n desi g n 
i n 1 c o h ort ( C o h ort 1) of healt h y  a d ult partici pa nts. A n o pti o nal c o h ort of healt h y  a d ult 
partici pa nts ( C o h ort 2) i n u p t o 4 cr oss o ver peri o ds, ma y be i ncl ude d t o per mit assess me nt of 
a n y of t he f oll o wi n g: re peat of a pre vi o usl y a d mi nistere d d ose le vel; st u d yi n g a d diti o nal d ose 
le vels as dictate d by t he e val uate d safet y, t olera bilit y, or P K of earlier d ose le vels; or a n y  
ot her assess me nt nee de d t o meet t he o b jecti ves of t his st u d y. A sec o n d o pti o nal c o h ort 
( C o h ort 3) e nr olli n g Ja pa nese partici pa nts i n u p t o 3 cr oss o ver peri o ds, ma y  be i ncl u de d.
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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A total of approximately 24 healthy adult participants will be randomized, up to
approximately 10 in Cohort 1, up to approximately 8 in optional Cohort 2, and up to 
approximately 6 Japanese participants in optional Cohort 3. The actual number of Japanese 
participants may be adjusted based on emerging data or operational factors, with a maximum 
sample size of up to 8 participants. Each participant, depending on the cohort to which they 
are enrolled, will be randomized to receive up to 5 and 4 single doses of PF-06954522 for 
Cohorts 1 and 2, respectively, and up to 2 placebo doses. In each period, approximately 8 and 
6 participants in Cohorts 1 and 2, respectively, will receive a single dose of PF-06954522, 
and approximately 2 participants will receive placebo. In the optional cohort of Japanese 
participants, each participant will be randomized to receive up to 2 single doses of 
PF-06954522 and 1 placebo dose. The actual dose levels and design of this optional cohort of 
Japanese participants will be decided based on emerging data. This cohort, if implemented, 
will not be part of dose escalation as the dose levels administered would have been 
investigated and deemed sufficiently safe in previous cohort(s). Full details will be provided 
to the investigator in writing, prior to dosing of this cohort. Participants who discontinue for 
non-safety reasons prior to completion of the study may be replaced, at the discretion of the 
PI and sponsor. The replacement participant(s) may or may not be required to complete all 
periods of the cohort in which they are participating at the discretion of the PI and sponsor.
Participants will be screened within 28 days of their first dose of study intervention (Period 1, 
Day 1). Participants will be admitted to the CRU on Day -1 of each study period and will 
remain in the CRU through at least the 72-hour assessments on Day 4. Participants may 
remain in the CRU after completion of Day 4 activities at the discretion of the investigator or 
if safety, tolerability, or PK data dictate the need to prolong confinement in the CRU. 
Participants will receive a single oral dose of PF-06954522 or placebo on Day 1 of each 
period. 
Between each dose administration to a given participant there will be a washout interval of at
least 7 days. The washout interval may be increased based on data emerging from previous 
cohorts/periods. Dose escalation will occur only after the previous dose level was 
demonstrated to be well tolerated with an acceptable safety profile based on review of the 
emerging safety and PK data (see Section 6.6.1). Dose levels will be escalated to bracket the 
expected clinical dose range, but the projected exposures will not exceed the predefined 
human exposure limits. An on-site follow-up visit and a telephone follow-up contact will 
take place 7-10 days and 28-35 days, respectively, after the last dose of study intervention in 
the final period, or after early discontinuation. At the discretion of the investigator, telephone 
follow-up contact may be substituted with an on-site visit in case of additional follow-up of 
open AEs or clinically significant laboratory findings. Therefore, the total planned duration 
of participation, from the Screening visit to the follow-up phone call, will be approximately 
13 weeks for Cohort 1, 12 weeks for optional Cohort 2 and 11 weeks for optional Cohort 3 
(if performed as a 3-way crossover).
Dosing of study intervention is anticipated to occur following a fast of at least 10 hours. Dose 
administration may also occur in the fed state (following a high-fat breakfast, see
Section 5.3.2), in order to explore any potential food effect on PF-06954522 PK. If this 
assessment is conducted, it is anticipated that the study intervention will be administered in 
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 3
l o w e n o u g h t o e ns ure hi g h c o nfi de nce i n partici pa nt safety, w hile s o me p har mac ol o gical 
effects are e x pecte d.
T he d ose ra n ge t o be st u die d was selecte d t o acc o u nt f or u ncertai nties i n t he pr ojecte d C eff
a n d t he pr ojecte d t hera pe utic d ose, w hile als o brac keti n g t he e x pecte d cli nicall y efficaci o us 
d ose ra n ge i n h u ma ns f or cli nicall y  rele va nt p har mac ol o gical acti vity a n d pr o vi di n g safet y 
c o vera ge f or a wi de ra n ge of P F - 0 6 9 5 4 5 2 2 d oses .
T he pr ojecte d e x p os ures of P F -0 6 9 5 4 5 2 2 f or eac h pla n ne d d ose le vel, as well as t he 
c orres p o n di n g safet y mar gi ns relati ve t o h u ma n e x p os ure li mits are s u m marize d i n Ta ble 3. 
T a ble 3.
Pre dicte d H u m a n E x p os ure a n d S afet y M ar gi ns F oll o wi n g 
A d mi nistr ati o n of Si n gle Or al D oses of P F- 0 6 9 5 4 5 2 2
D ose ( m g) a
Pre dicte d H u m a n P F -0 6 9 5 4 5 2 2 E x p os ure
Pre dicte d S afet y M ar gi n
T ot al C m a x b
( n g/ m L)
T ot al 
A U C 2 4 b
( n g• h/ m L)
U n b o u n d 
C m a x c
( n g/ m L)
U n b o u n d 
A U C 2 4 c
( n g• h/ m L)
C m a x d
A U C 2 4 d
a.
Base d o n t he a vaila ble safet y, t olera bilit y a n d P K data, d ose escalati o n ma y be a dj uste d t o d oses ot her t ha n 
t h ose o utli ne d a b o ve wit h i nter me diate d oses e val uate d i nstea d of or i n a d diti o n t o t he pla n ne d d ose le vels wit h 
i ncre me nts bei n g a p pr o xi matel y ≤½- l o g (ie, a p pr o xi matel y 3. 3-f ol d) w hile al wa ys f oll o wi n g d ose escalati o n a n d 
st o p pi n g r ules o utli ne d i n Secti o n 6. 6. 1 .
b.
H u ma n P K pr ofiles were pre dicte d usi n g a 1 -c o m part me nt P K m o del wit h first -or der a bs or pti o n a n d 
eli mi nati o n. T he pr ojecte d h u ma n P F -0 6 9 5 4 5 2 2 P K para meters o utli ne d i n Secti o n 4. 3. 1 were use d i n t he 
m o del.
c.
U n b o u n d e x p os ure val ues calc ulate d after c orrecti n g f or plas ma pr otei n bi n di n g i n h u ma ns (
).
d.
Safet y mar gi ns at t he pr o p ose d d oses were calc ulate d base d o n t he h u ma n e x p os ure li mits (total 
) w hic h were base d o n t he N O A E L e x p os ures i n 
t he 8 -wee k N H P G L P t o xicit y st u d y after c orrecti n g f or s pecies differe nce i n plas ma pr otei n bi n di n g.
Be y o n d t he starti n g d ose, t he pla n ne d d ose escalati o n pr oce d ure will be dictate d b y  t he r ules
s u m marize d i n Secti o n 6. 6. 1 . Assess me nt of t he safet y , t olera bilit y, a n d P K after eac h si n gle 
d ose le vel will be c o n d ucte d bef ore escalati n g t o t he ne xt d ose le vel. T he 
d ose/e x p os ure -escalati o n i ncre me nts are pla n ne d t o be u p t o a p pr o xi mate se mi-l o garit h mic 
i ncreases i n e x p os ure fr o m t he pre vi o us hi g hest d ose le vel t hat has bee n e val uate d. If 
e x p os ure e xcee ds t he pr ojecte d t hera pe utic ra n ge, or if c ha n ges i n safet y para meters are 
o bser ve d, s maller d ose -escalati o n ste ps m a y be i m ple me nte d. D ose -escalati o n is e n visi o ne d 
t o pr ocee d u p t o t he hi g hest d ose dee me d t o be well t olerate d wit h a n acce pta ble safety 
pr ofile, ac hie ve me nt of plas ma e x p os ures e q ui vale nt t o t he P K st o p pi n g li mits (see 
Secti o n 6. 6. 1 ).
T he act ual d ose le vels, tar get e x p os ures, a n d/ or d ose le vel i ncre me nts ma y  be a dj uste d 
( hi g her or l o wer) d uri n g t he st u d y base d o n e mer gi n g h u ma n safet y, t olera bilit y , a n d P K 
data, b ut pr ojecte d e x p os ures will n ot e xcee d t he pre defi ne d h u ma n e x p os ure li mits. D ose 
le vels ma y als o be re peate d if warra nte d. 
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
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Page 34
When the assessment of the effect of food on the PK of PF-06954522 is conducted, the dose 
level will be selected based on emerging safety, tolerability, and PK data from previous 
periods of this study. This will be assessed at a dose level that has been previously 
administered fasted within the same cohort (as outlined in Section 4.2).
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study 
or last scheduled procedure shown in the SoA for the last participant in the trial globally.
A participant is considered to have completed the study if they have completed all periods of 
the study, including the last visit or the last scheduled procedure shown in the SoA and any 
requested unplanned visits.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. If a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation in the study is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants of non-childbearing potential aged 18 to 65 years, 
inclusive, at screening who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, laboratory tests, and cardiac 
monitoring. 
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Other Inclusion Criteria:
2. BMI of 16-30.5 kg/m2; and a total body weight >50 kg (110 lb).
Japanese participants only: participants enrolling as Japanese must have 
4 biological Japanese grandparents who were born in Japan. A lower entry weight of 
090177e19e0f3afc\Approved\Approved On: 19-Jul-2023 01:55 (GMT)


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 5
4 5 k g ma y  be c o nsi dere d if t he t otal bl o o d v ol u me c ollecti o n f or t his c o h ort d oes 
N O T e xcee d 3 6 0 m L o ver a n 8 -wee k peri o d. 
3.
Willi n g a n d a ble t o c o m pl y  wit h all sc he d ule d visits, treat me nt pla n, la b orat or y tests, 
lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1 , w hic h 
i ncl u des c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he IC D a n d i n 
t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps y c hiatric, ne ur ol o gic al, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, asy m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V , 
H Bs A g, H Bc A b, or H C V A b. H ist or y of he patitis B vacci nati o n wit h a n is olate d 
p ositi ve H Bs A b res ult is all o we d.
2.
Pers o nal or fa mil y hist or y of M T C or M E N 2, or partici pa nts wit h s us pecte d M T C per 
t he i n vesti gat or’s j u d ge me nt.
3.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y or ot her c o n diti o ns t hat ma y 
i ncrease t he ris k of st u d y partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he 
partici pa nt i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of 
 
w hic h are pr o hi bite d wit hi n 1 4 da y s pl us 5 half -li ves pri or t o t he first d ose of st u d y 
i nter ve nti o n. (Refer t o Secti o n 6. 9 Pri or a n d C o nc o mita nt T hera p y f or a d diti o nal 
details ).
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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Page 36
Prior/Concurrent Clinical Study Experience:
5. Previous administration with an investigational product (drug or vaccine) within 
30 days (or as determined by the local requirement) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer). Participation in 
studies of other investigational products (drug or vaccine) at any time during their 
participation in this study.
Diagnostic Assessments:
6. A positive urine drug test at screening or admission.
7. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for 
participants <60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following 
at least 5 minutes of supine rest. If systolic BP is ≥140 or 150 mm Hg (based on age) 
or diastolic ≥90 mm Hg, 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. 
8. Renal impairment as defined by an eGFR of <75 mL/min/1.73 m². Based upon 
participant age at screening, eGFR is calculated using the recommended CKD-EPI 
equations in Section 10.7.2 to determine eligibility (Screat-based formula) and to 
provide a baseline (Screat-Scys combined formula) to quantify subsequent kidney 
safety events. For eligibility assessment based upon estimated renal function, the 
higher of the screening and baseline eGFR values may be used.
9. Standard 12-lead ECG at Screening that demonstrates clinically relevant 
abnormalities that may affect participant safety or interpretation of study results (eg, 
QTcF >450 ms, complete LBBB, signs of an acute or indeterminate age myocardial
infarction, ST-T interval changes suggestive of myocardial ischemia, second- or 
third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF
exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the 
average of the 3 QTcF or QRS values used to determine the participant’s eligibility.
Computer-interpreted ECGs should be overread by a physician experienced in 
reading ECGs before excluding a participant.
10. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary: 
!
ALT, AST, or bilirubin ≥1.05 × ULN. Participants with an elevated total bilirubin 
consistent with Gilbert’s Disease may have a direct bilirubin measured and would 
be eligible for this study provided the direct bilirubin level is ≤ULN;
!
TSH % ULN 
!
HbA1c ≥6.5%;
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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!
Hematuria as defined by ≥1+ heme on urine dipstick;
!
Albuminuria as defined by urine albumin/creatinine ratio (UACR) >30 mg/g.
Other Exclusion Criteria:
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 (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
12. Use of tobacco/nicotine containing products in excess of the equivalent of 
5 cigarettes/day or 2 chews of tobacco/day.
13. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Contraception
The investigator or their designee, in consultation with the participant, will confirm that 
the participant is utilizing an appropriate method of contraception for the individual 
participant and their partner(s) from the permitted list of contraception methods (see 
Appendix 4, Section 10.4.4) and will confirm that the participant has been instructed in 
its consistent and correct use. The investigator or designee will advise the participant to 
seek advice about the donation and cryopreservation of germ cells prior to the start of 
study intervention, if applicable.
At time points indicated in SoA, the investigator or designee will inform the participant 
of the need to use highly effective contraception consistently and correctly and document 
the conversation and the participant’s affirmation in the participant’s chart. Participants 
need to affirm their consistent and correct use of at least 1 of the selected methods of 
contraception, considering that their risk for pregnancy may have changed since the last 
visit. 
In addition, the investigator or designee will instruct the participant to call immediately if 
the selected contraception method is discontinued and document the requirement to use 
an alternate protocol-specified method, including if the participant will no longer use 
abstinence as the selected contraception method, or if pregnancy is known or suspected in 
the participant or partner.
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
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5.3.2. Meals and Dietary Restrictions
!
Participants must abstain from all food and drink (except water) for at least 8 hours 
prior to all safety laboratory evaluations.
!
Participants must abstain from all food and drink (except water) for at least 10 hours 
prior to the collection of the predose PK sample.
!
Water is permitted until 1 hour prior to study intervention administration. Water may 
be consumed without restriction beginning 1 hour after dosing. Noncaffeinated drinks 
(except grapefruit or grapefruit-related citrus fruit juices (see below) may be 
consumed with meals and the evening snack.
Dosing under fasted conditions (Day 1 only):
!
The standard morning breakfast will not be offered on Day 1. Participants will remain 
fasted for 4 hours following dosing.
Dosing under fed conditions (Day 1 only):
!
A morning meal will be served to participants approximately 30 minutes prior to 
dosing and is expected to be completed approximately 10 minutes prior to dosing. 
Participants will be encouraged to consume the entire meal.
!
For planned assessment of food effect, this morning meal will be a high-fat 
(approximately 50% of total caloric content of the meal) and high-calorie 
(approximately 800-1000 calories) breakfast. The breakfast will consist of 
approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat 
calories. An example test meal would be: 2 eggs fried in butter, 2 strips of bacon 
(or 50 g of meat or sausage), 2 slices of toast with butter, 4 ounces (approximately 
112 grams) of hash brown potatoes, and 8 fluid ounces (240 mL) of whole milk.
!
A standard breakfast may be provided during other study periods/cohorts, if 
deemed necessary to meet study objectives (see Section 4.1). If this is the case, 
details will be provided to the investigator in writing. 
!
While inpatient, the meals consumed are expected to follow the restrictions outlined 
below:
!
No food will be allowed for at least 4 hours post-dose.
!
Lunch will be provided approximately 4 hours after dosing.
!
Dinner will be provided approximately 9 to 10 hours after dosing.
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PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 39
!
Participants may delay or skip postdose meals or be offered an alternative meal in 
case of nausea or vomiting. In such cases, the proportion of each meal consumed 
by the participants will be recorded. 
!
An evening snack may be permitted.
!
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 the dosing 
day.
!
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. 
!
With the exception of the standard high-fat, high-calorie breakfast to be consumed 
during food effect assessment, while participants are confined, their total daily 
nutritional composition should be approximately 55% carbohydrate, 30% fat, and 
15% protein, except when the study intervention is administered with high-fat, 
high-calorie breakfast. The daily caloric intake per participant should not exceed 
approximately 3200 kcal.
5.3.3. Caffeine, Alcohol, and Tobacco
!
Participants will abstain from caffeine -containing products for 24 hours prior to the 
start of dosing until collection of the final PK sample of each study period. 
!
Participants will abstain from alcohol for 24 hours prior (or as specified above for red 
wine) to admission to the CRU and continue abstaining from alcohol until collection 
of the final PK sample of each study period. Participants may undergo an alcohol 
breath test or blood alcohol test at the discretion of the investigator.
!
Participants will abstain from the use of tobacco- or nicotine -containing products for 
24 hours prior to dosing and during confinement in the CRU.
5.3.4. Activity
!
Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 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;
090177e19e0f3afc\Approved\Approved On: 19-Jul-2023 01:55 (GMT)


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 0

Partici pa nt s will be c o nfi ne d t o t he pr oce d ure r o o m f or t he first 4 h o urs after d osi n g 
o n Da y 1 d uri n g c o nti n u o us car diac m o nit ori n g, e xce pt t o use t he bat hr o o m. After 
t his, if t he e q ui p me nt set u p all o ws, partici pa nt s ma y be a m b ulat or y d uri n g t he E C G 
m o nit ori n g peri o d, b ut s h o ul d n ot e n ga ge i n stre n u o us acti vities. If e q ui p me nt d oes 
n ot all o w a m b ulati o n, a p pr o priate acc o m m o dati o ns will be ma de b y  t he i n vesti gat or 
site t o facilitate c o nti n u o us mo nit ori n g ( e g, be dsi de uri nals s h o ul d be pr o vi de d t o 
acc o m m o date partici pa nt s’ e xcret or y nee ds).
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e nr olle d i n t he st u d y. Sc ree n fail ure data are c ollecte d a n d re mai n as 
s o urce a n d are n ot re p orte d o n t he C R F .
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y be 
rescree ne d at t he discreti o n of t he PI i n c o ns ultati o n wit h t he me dical mo nit or . 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal a n d, me dical de vices, a n d ot her 
i nter ve nti o ns (e g, s ur gical a n d be ha vi oral) i nte n de d t o be a d mi nistere d t o t he st u d y 
partici pa nts d uri n g t he st u d y c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o P F -0 6 9 5 4 5 2 2 a n d place b o .
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
St u d y I nter ve nti o n(s)
I nter ve nti o n 
N a me
P F -0 6 9 5 4 5 2 2
Place b o
T y pe
Dr u g
Dr u g
Use
E x peri me ntal
Place b o
I M P or 
NI M P/ A x M P
I M P
I M P
D ose 
F or m ul ati o n
B ul k p o w der f or e xte m p ora ne o us pre parati o n of 
oral s us pe nsi o ns
B ul k p o w der f or e xte m p ora ne o us pre parati o n of 
oral s us pe nsi o ns
U nit D ose 
Stre n gt h(s)
Pl a n ne d s us pe nsi o n d oses ra n gi n g fr o m 
m g
0 m g
D os a ge Le vel(s)
Si n gle asce n di n g d oses 
 m g (see 
Secti o n 1. 2 a n d Secti o n 4. 3 . 4) 
0 m g
R o ute of 
A d mi nistr ati o n
Oral
Oral
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C
C
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 1
St u d y I nter ve nti o n(s)
S o urci n g
Pr o vi de d b y t he s p o ns or
Pr o vi de d b y t he s p o ns or
P ac k a gi n g a n d 
L a beli n g
St u d y i nter ve nti o n will be pr o vi de d i n b ul k
p o w der f or e xte m p ora ne o us pre parati o n of oral 
s us pe nsi o ns. Eac h b ottle will be la bele d as 
re q uire d per c o u ntr y re q uire me nt.
St u d y i nter ve nti o n will be pr o vi de d i n b ul k 
p o w der f or e xte m p ora ne o us pre parati o n of oral 
s us pe nsi o ns. Eac h b ottle will be la bele d as 
re q uire d per c o u ntr y re q uire me nt.
S R S D
I B
I B
St u d y Ar m(s)
A r m  Title
C o h ort 1
C o h ort 2 ( O pti o nal)
C o h ort 3 ( O pti o nal)
A r m  Descri pti o n
Partici pa nts ma y recei ve 
u p t o 5 d ose le vels of 
P F -0 6 9 5 4 5 2 2 a n d 
matc hi n g place b o. D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses 
t o be deter mi ne d.
Partici pa nts ma y recei ve 
u p t o 4 d ose le vels of 
P F -0 6 9 5 4 5 2 2 a n d 
matc hi n g place b o. D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses 
t o be deter mi ne d.
Partici pa nts ma y recei ve 
u p t o 3 d ose le vels of 
P F -0 6 9 5 4 5 2 2 a n d 
matc hi n g place b o. D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses t o 
be deter mi ne d.
P F - 0 6 9 5 4 5 2 2 a n d place b o will be pr o vi de d b y Pfizer as b ul k p o w ders f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns at t he C R U.

P F -0 6 9 5 4 5 2 2 or place b o oral s us pe nsi o ns will be e xte m p ora ne o usl y pre pare d f or 
si n gle oral d oses ra n gi n g fr o m 
m g .
P F- 0 6 9 5 4 5 2 2 a n d place b o will be prese nte d t o t he partici pa nt s i n i n di vi d ual d osi n g 
c o ntai ners.
6. 1. 1. A d mi nistr ati o n
F or faste d peri o ds:

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nts will recei ve st u d y  
i nter ve nti o n at a p pr o xi matel y 0 8 0 0 h o urs ( pl us or mi n us 2 h o urs) wit h o ut brea kfast 
o n Da y  1.
F or fe d peri o d(s):

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nts will recei ve brea kfast 
a p pr o xi matel y 3 0 mi n utes pri or t o d osi n g o n Da y 1 w hic h is t o be c o m plete d wit hi n 
a p pr o xi matel y 2 0 mi n utes as o utli ne d i n Secti o n 5. 3. 2 . T he partici pa nts will t he n 
recei ve st u d y i nter ve nti o n a p pr o xi matel y 1 0 mi n utes after c o m pleti o n of t he meal at 
a p pr o xi matel y 0 8 0 0 h o urs ( pl us or mi n us 2 h o urs).
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On Day 1 of each period, investigator site personnel will administer a single oral dose of 
study intervention with ambient temperature water to a total volume of approximately 
240 mL. Study intervention will be administered 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.
Administration of study intervention(s) at the site will be performed by an appropriately 
qualified and trained member of the study staff as allowed by local, state, and institutional 
guidance. 
Following administration of study intervention(s) at the site, participants will be observed for 
up to 2 hours post-dose by an appropriately qualified and trained member of the study staff. 
Appropriate medication and other supportive measures for management of a medical 
emergency will be available in accordance with local guidelines and institutional guidelines.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions (eg, 
temperature) have been maintained during transit for all study interventions received 
and any discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention.
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized site staff. At 
a minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented upon 
return to business.
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to the labeled storage conditions, 
as soon as possible. Once an excursion is identified, the study intervention must be 
quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the excursion definition and information to
report for each excursion will be provided to the site in the PCRU site procedures.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
6. Study interventions should be stored in their original containers.
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7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records), such as the IPAL or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the PCRU’s 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.
PF-06954522 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.
PF-06954522 and placebo will be prepared by qualified unblinded site personnel according 
to the EDR. Blinded study intervention will be administered in a blinded fashion to the 
participant. 
6.3. Assignment 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.
6.4. Blinding
This is a double-blind (sponsor-unblinded) study. 
6.4.1. Blinding of Participants
Participants will be blinded to their assigned study intervention.
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6.4.2. Blinding of Site Personnel
Investigators and other site staff will be blinded to participants’ assigned study intervention. 
Participants will be assigned to receive study intervention according to the assigned treatment 
group from the randomization scheme. 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 will be responsible for the 
preparation and dispensing of all study intervention and will endeavor to ensure that there are 
no differences in time taken to dispense or visual presentation, following randomization or 
dispensing. This third party will instruct the participant to avoid discussing the taste, dosing 
frequency, or packaging of the study intervention with the investigator. 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
PCRU pharmacy staff responsible for preparing all study interventions will be unblinded. 
PCRU site staff providing technical system support to pharmacy staff and supporting blinded 
laboratory data processes will be unblinded. These site staff providing system support will 
not be involved in any data collection or clinic floor activities.
6.4.3. Blinding of the Sponsor
As this is a sponsor-open study, the sponsor 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 modeling, and/or supporting clinical development.
Individual participant-level unblinded data will be reviewed by a designated limited number 
of sponsor personnel.
6.4.4. Sensitive Clinical Data 
Sensitive clinical data are data collected in this study that have the potential to unblind a 
participant’s treatment assignment. Access to sensitive clinical data will be restricted to 
authorized individuals until the study has been unblinded. The following data variables are 
considered sensitive clinical data:
!
Study intervention assignments (PF-06954522 or placebo);
!
Individual PF-06954522 PK data.
6.4.5. Breaking the Blind 
The method for breaking the blind in this study 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 study medical monitor prior to 
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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 CRF.
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. Other Pfizer 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 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.
6.5. Study Intervention Compliance
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second qualified member of the study site staff.
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. Study site personnel will examine each participant’s mouth to ensure that 
the study intervention was ingested.
6.6. Dose Modification
The decision to proceed to the next dose level of PF-06954522 (either an increase, decrease, 
or repeat of a previous dose level) will be made by the study team and the investigator based 
on observed safety, tolerability, and preliminary PK data obtained at the prior dose level. At 
least 8 and 6 participants (including at least 1 placebo participant) must complete the prior 
dose level in Cohort 1 and 2, respectively. PK data through at least 24 hours post-dose and 
safety and tolerability data through at least 48 hours post-dose of the current period will be 
reviewed. Cumulative safety and tolerability from all previous periods will also be reviewed.
The dosing schedule may also be adjusted to expand a dosing cohort to further evaluate 
safety, tolerability, and/or PK findings at a given dose level or to add cohorts to evaluate 
additional dose levels or repeat dose levels. The study procedures for these additional 
participant(s)/cohort(s) will be the same as that described for other study participants/cohorts
unless otherwise indicated.
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 6
6. 6. 1. D ose Esc al ati o n a n d St o p pi n g R ules 
D ose escalati o n st o p pi n g r ules will be use d t o deter mi ne w het her t he ma xi mal t olerate d d ose 
has bee n attai ne d. D ose escalati o n ma y  be st o p pe d if it is deter mi ne d t hat t he li mits of safet y 
a n d/ or t olera bilit y ha ve bee n reac he d. T his decisi o n will be ma de after a disc ussi o n ta kes 
place bet wee n t he s p o ns or st u d y  tea m a n d t he i n vesti gat or. T he sp o ns or st u d y  tea m ma y n ot 
o verr ule t he i n vesti gat or’s decisi o n t o st o p d ose escalati o n. If d ose escalati o n is st o p pe d 
beca use of a n y of t hese criteria, a d diti o nal c o h orts ma y recei ve t he sa me or l o wer d oses of 
t he st u d y i nter ve nti o n.
T he d ose escalati o n will be ter mi nate d base d o n t he f oll o wi n g criteria:

If 5 0 % or m ore of t he partici pa nt s recei vi n g acti ve dr u g at a gi ve n d ose le vel ( b ut n ot 
partici pa nt s recei vi n g place b o) de vel o p si milar cli nicall y si g nifica nt la b orat or y, E C G, 
or vital si g n a b n or malities, i n t he sa me or ga n class, i n dicati n g d ose-li miti n g 
i nt olera nce.

Se vere n o nseri o us A Es, c o nsi dere d as, at least, p ossi bl y relate d t o st u d y i nter ve nti o n
a d mi nistrati o n, i n 2 partici pa nts at a gi ve n d ose le vel ( b ut n ot partici pa nts recei vi n g 
place b o), i n de pe n de nt of wit hi n or n ot wit hi n t he sa me s y ste m or ga n class, i n dicati n g 
d ose -li miti n g i nt olera nce.

D osi n g will be pa use d f or a n y S A E t hat occ urs i n a partici pa nt recei vi n g acti ve 
treat me nt u ntil ca usalit y is f ull y assesse d b y t he PI a n d s p o ns or. D osi n g ma y r es u me 
if t he S A E is deter mi ne d t o be n ot dr u g-relate d by t he PI a n d s p o ns or. If t he S A E is 
deter mi ne d t o be eit her dr u g-relate d or u n k n o w n, eit her d osi n g will cease or t he S A E 
will be e val uate d b y t he s p o ns or’s pr ot oc ol re vie w c o m mittee ( or si milar re vie w 
g r o u p), w hic h is i n de pe n de nt of t he st u d y tea m a n d i n vesti gat ors. If t he pr ot oc ol 
re vie w c o m mittee deter mi nes t hat d osi n g ma y res u me, a pla n t hat miti gates ris ks t o 
partici pa nt s wit h t he res u m pti o n of d osi n g will be i m ple me nte d. S uc h a pla n c o ul d 
i ncl u de a re visi o n of i ncl usi o n/e xcl usi o n criteria, re peati n g or re d uci n g t he d ose, or 
a d di n g a p pr o priate safet y m o nit ori n g.

It is deter mi ne d t hat t he li mit of safet y a n d/ or t olera bilit y has bee n reac he d. T his 
decisi o n will be ma de f oll o wi n g disc ussi o ns bet wee n t he st u d y tea m a n d t he 
i n vesti gat or.

Ot her fi n di n gs t hat, at t he discreti o n of t he st u d y t ea m a n d i n vesti gat or, i n dicate t hat 
d ose escalati o n s h o ul d be halte d .

If, at a ny d ose le vel, t he a vera ge e x p os ure reac hes or e xcee ds t he P K st o p pi n g li mits : 
. 

If, base d o n t he o bser ve d data, t he gr o u p mea n Cma x or A U C ( base d o n t otal plas ma 
c o nce ntrati o n) of t he ne xt pla n ne d d ose is pr ojecte d t o e xcee d t he escalati o n li mits, 
t hat d ose will n ot be e x pl ore d. M o difie d d oses ma y be e x pl ore d if t he y are n ot 
e x pecte d t o e xcee d P K st o p pi n g criteria.
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 7

T he hi g hest d ose e val uate d i n t his st u d y  will n ot e xcee d  
 m g.
Pr o gressi o n t o t he ne xt d ose will occ ur if t he last d ose was well t olerate d a n d after 
satisfact or y re vie w of t he a vaila ble safety a n d P K data.
6. 7. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y partici pati o n.
6. 8. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of P F - 0 6 9 5 4 5 2 2 pr ojecte d t o res ult i n e x p os ures greater t ha n t he 
defi ne d P K st o p pi n g li mit of 
, (see 
Secti o n 6. 6. 1 ) wit hi n a 2 4-h o ur ti me peri o d will be c o nsi dere d a n o ver d ose. 
T here is n o s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or/treati n g p h ys icia n s h o ul d:
1.
C o ntact t he st u d y me dical m o nit or wit hi n 2 4 h o urs.
2.
Cl osel y  m o nit or t he partici pa nt f or a ny A E s/ S A Es a n d la b orat or y a b n or malities as 
me dicall y  a p pr o priate a n d f oll o w u p u ntil res ol uti o n , sta bilizati o n, t he e ve nt is 
ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w -u p (as defi ne d i n Secti o n 7. 3 ).
3.
D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E.
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 2 da ys fr o m t he date of t he last d ose of 
st u d y i nter ve nti o n if re q ueste d b y t he st u d y me dical m o nit or ( deter mi ne d o n a 
case-b y -case basis).
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he st u d y me dical m o nit or as nee de d base d o n t he cli nical e val uati o n of t he 
partici pa nt.
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of 
 w hic h 
are pr o hi bite d wit hi n 1 4 da y s pl us 5 half -li ves pri or t o t he first d ose of st u d y i nter ve nti o n (see 
A p pe n di x 9 ). 
Li mite d use of n o n prescri pti o n me dicati o ns t hat are n ot belie ve d t o affect partici pa nt safet y  
or t he o verall r es ults of t he st u d y ma y be per mitte d o n a case-b y -case basis f oll o wi n g 
a p pr o val b y t he s p o ns or . Aceta mi n o p he n/ paraceta m ol ma y  be use d at d oses of ≤1 g/ da y .
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
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Females taking hormone replacement therapy may be eligible to participate in this study if 
they are willing to discontinue therapy at least 28 days prior to the first dose of study 
treatment and remain off hormonal therapy for the duration of the study. 
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: AEs or other 
(administrative) reasons.
Discontinuation of study intervention does not represent withdrawal from the study. If study 
intervention is permanently discontinued, the participant should remain in the study to be 
evaluated for ongoing AEs. See the SoA for data to be collected at the time of 
discontinuation of study intervention and follow-up for any further evaluations that need to 
be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, further study follow-up, and/or 
future collection of additional information.
7.1.1. Potential Cases of Acute Kidney Injury
Participants exposed to IMP demonstrating transient or sustained increase in Screat (with 
decrease in Screat-based eGFR or eCrCl) require expedited evaluation to differentiate AKI 
from DICI. DICI is defined as transporter-mediated effect related to altered renal tubular 
creatinine handling without histological injury.
AKI may be due to one or more types of injury, including DIKI. Differentiation of DIKI 
from other causes of AKI and from DICI may require clinical, radiographic, histopathologic, 
and laboratory assessments, as well as nephrology consultation.
Follow-up Assessments
The participant should return to the site for evaluation as soon as possible, preferably within 
48 hours of awareness of the abnormal results. 
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Evaluation should include physical examination, laboratory tests, detailed medical and 
surgical history, review of all medications (including recreational drugs and supplements 
[herbal]), family history, sexual history, travel history, blood transfusion, and potential 
occupational exposure to chemicals. 
Laboratory assessments should include simultaneous serum cystatin C (Scys) and serum 
creatinine (Screat) tests. Estimates of eGFR, eCrCl and Screat-based eGFR and combined 
Screat-Scys-based eGFR should also be derived using the appropriate equation described in 
Appendix 7.
Assessments of urine albumin-to-creatinine ratio or urine volume may also be performed as 
appropriate.
If appropriate, nephrology consultation may be recommended to facilitate differentiation of 
renal parenchymal disease, pre-renal azotemia, and post-renal obstruction. 
Differentiating Acute Kidney Injury from DICI
A confirmed Screat increase is defined as:
(i) ≥0.3 mg/dL (≥26.5 μmol/L) within 48 hours OR 
(ii) confirmed Screat increase ≥1.5 times baseline (known or suspected to have occurred 
within the prior 7 days). 
Based on the assessments performed, suspected AKI (including DIKI) may be differentiated 
from DICI as follows.
Adult participants
AKI (including DIKI)
Any one of the below
DICI
Scys & Screat
Simultaneous, confirmed serum cystatin 
C (Scys) increase and confirmed Screat 
increase 
Confirmed Screat increase without 
confirmed increase in reflex Scys 
AND 
Confirmed Screat-based eGFR 
decrease without confirmed combined 
Screat-Scys-based eGFR decrease.
eGFR
Decrease in Screat-based eGFR and 
combined Screat-Scys-based eGFR (when 
available)
Albuminuria or 
proteinuria
Confirmed albuminuria increase (see 
Appendix 7 for Grades A1 to A3 
quantitation)
Urine volume
Urine volume <0.5 mL/kg/h for 
6 consecutive hours
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Regardless of the presence or absence of increase in Screat, DIKI and other causes of AKI 
may be suspected if either there is (i) new-onset or worsening albuminuria or proteinuria are 
detected.
All confirmed cases of clinically relevant decrease in kidney function should be considered 
potential cases of DIKI if no other reason for the kidney function abnormalities has been 
found.
7.1.2. Liver Injury
A participant who meets any of the following will be withdrawn from the study 
intervention.[16]
!
ALT or AST >8 × ULN;
!
ALT or AST >5 × ULN for more than 2 weeks;
!
ALT or AST >3 × ULN and (T bili >2 × ULN or INR >1.5);
!
ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).
See Section 10.6 for Potential Cases of Drug Induced Liver Injury.
7.1.3. ECG Changes
A participant who meets either bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from the study intervention. 
!
QTcF >500 ms.
!
Change from baseline: QTcF >60 ms and QTcF >450 ms.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE.
7.1.4. COVID-19 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE (as 
appropriate) and appropriate medical intervention provided. Study treatment should continue 
unless the investigator/treating physician is concerned about the safety of the participant, in 
which case temporary or permanent discontinuation may be required. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:
!
Refused further study procedure;
!
Lost to follow-up;
!
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 the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1 for 
disclosure of future information, no further evaluations will be performed and no additional 
data will be collected. The sponsor may retain and continue to use any data collected before 
such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
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the participant is alive or dead) is being measured, publicly available information should be 
used to determine vital status only as appropriately directed in accordance with local law.
7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up- if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
!
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;
!
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;
!
Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative and Baseline Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
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A participant who qualified for this protocol but did not enroll from an earlier cohort/group
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, eg, retained research samples, 
may not need to be repeated, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
Any safety, laboratory or analyte results that have been collected for the purposes of this 
study and could unblind the study will not be reported to investigative sites or other blinded 
personnel until the study has been unblinded.
If done around the time of a blood draw, ECGs and vital sign assessments (BP and pulse rate) 
should be collected before the blood draw. 
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in Cohorts 1, 2 and 3 of this 
study are approximately 545, 440 and 340 mL, respectively. The actual collection times of 
blood sampling may change. Additional blood samples may be taken for safety assessments
at times specified by Pfizer, provided the total volume taken during the study does not exceed 
550 mL during any period of 56 consecutive days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.2. Efficacy Assessments
Efficacy parameters are not evaluated in this study. 
8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety 
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
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8.3.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms.
Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
Physical examination findings collected during the study will be considered source record 
and will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.4.1 to 8.4.3.
8.3.2. Vital Signs
8.3.2.1. Blood Pressure and Pulse Rate
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements. When triplicate measurements of supine BP or 
pulse rate are required per SoA, measurements should be collected 2-4 minutes apart.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
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8.3.2.2. Respiratory Rate
Respiratory rate will be measured after approximately 5 minutes of rest in a supine position 
by observing and counting the respirations of the participant for 30 seconds and multiplying
by 2. When BP is to be taken at the same time, respiration measurement will be done during
the 5 minutes of rest and before BP measurement.
8.3.2.3. Body Temperature
Body temperature will be measured orally. No eating, drinking, or smoking is allowed for 
15 minutes prior to the measurement.
8.3.3. Electrocardiograms
Standard 12-lead ECGs will be collected at times specified in the SoA section of this
protocol using an ECG system that automatically calculates the HR and measures PR, QT, 
QTcF, and QRS intervals. All scheduled ECGs should be performed after the participant has 
rested quietly for at least 5 minutes in a supine position. 
Triplicate 12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average of 
the triplicate ECG measurements collected at -1.0, -0.5, and 0 hours pre-dose on Day 1 of 
each period will serve as each participant’s baseline QTcF value. 
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 postdose QTcF interval is increased by 
≥60 ms from the baseline and is >450 ms; or b) an absolute QT value is ≥500 ms for any 
scheduled ECG. If either of these conditions occurs, then 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.
For single ECG collection, additional ECG monitoring will occur if a) a postdose QTcF
interval is increased by ≥60 ms from the baseline and is >450 ms; or b) an absolute QT value 
is ≥500 ms for any scheduled ECG. If either of these conditions occurs, then 2 additional 
ECGs will be collected approximately 2 to 4 minutes apart to confirm the original 
measurement. If the QTcF values from these repeated ECGs remain above the threshold 
value, then a single ECG must be repeated at least hourly until QTc values from 2 successive 
ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTcF interval remains ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG for greater than 4 hours (or sooner, at 
the discretion of the investigator); or c) QTcF value get progressively longer, the participant
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTcF
values do not return to less than the criteria listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
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same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 8.
8.3.3.1. Continuous Cardiac Monitoring by Telemetry
All abnormal rhythms will be recorded and reviewed by the study physician for the presence 
of rhythms of potential clinical concern. The time, duration, and description of the clinically 
significant event will be recorded in the CRF. 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 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. This may be done immediately prior to dosing 
or at some 2-hour continuous interval in the 24 hours 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, it is expected that the telemetry leads will 
be in place and the system connected prior to dosing.
8.3.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition.
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within 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 study medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
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See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
DILI.
See Appendix 7 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities.
Participants may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before undergoing any study-related procedure and/or receiving study 
intervention), through and including a minimum of 28 calendar days, except as indicated 
below, after the last administration of the study intervention.
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
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If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has concluded study participation, and they
consider the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available.
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
8.4.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
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8.4.3. Follow-up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up- information will include a description of the event in sufficient detail 
to allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3.
8.4.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.4.5.1. Exposure During Pregnancy
An EDP occurs if:
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!
A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.
!
A male participant who is receiving or has discontinued study intervention
inseminates a female partner.
!
A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP:  
!
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.
!
A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then inseminates his female 
partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
!
If EDP occurs in a participant/participant’s partner, the investigator must report this 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form regardless of whether an SAE has occurred. Details of the pregnancy will be 
collected after the start of study intervention and until 28 days after the last dose of 
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 report is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial report. In the case of a live birth, the structural integrity of the neonate 
can be assessed at the time of birth. In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
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demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 
!
Spontaneous abortion including miscarriage and missed abortion should be reported 
as an SAE;
!
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if: 
!
A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
!
A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion, inhalation, or skin contact. 
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When EDB occurs in the setting of environmental exposure, 
the exposure information does not pertain to the participant enrolled in the study, so the 
information is not recorded on a CRF. However, a copy of the completed report is 
maintained in the investigator site file.
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
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8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 24 
hours of the investigator’s awareness using the CT SAE Report Form regardless of whether 
there is an associated SAE. Since the information about the occupational exposure does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed report is maintained in the investigator site file.
8.4.6. Cardiovascular and Death Events
Not applicable.
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.4.8. Adverse Events of Special Interest
Not applicable.
8.4.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.4.9. Medical Device Deficiencies
Not Applicable.
8.4.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Medication errors are recorded and reported as follows:
Recorded on the 
Medication Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the medication error
Only if associated with an 
SAE
Medication errors include:
!
Medication errors involving participant exposure to the study intervention;
!
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
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!
The administration of expired study intervention;
!
The administration of an incorrect study intervention;
!
The administration of an incorrect dosage;
!
The administration of study intervention that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, such medication errors occurring to a study participant are recorded on the 
medication error page of the CRF, which is a specific version of the AE page and, if 
applicable, any associated serious and nonserious AE(s), are recorded on the AE page of the 
CRF.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. Pharmacokinetics 
Blood samples of approximately 4 mL to provide approximately 1.6 mL of plasma, will be 
collected for measurement of plasma concentrations of PF-06954522 as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual times may change but the actual date and 
time (24-hour clock time) of each sample will be recorded.
All efforts will be made to obtain the samples at the exact nominal time relative to dosing.
Collection of samples up to and including 10 hours after dose administration that are
obtained within 10% of the nominal time relative to dosing (eg, within 6 minutes of a 
60-minute sample) will not be captured as a protocol deviation, as long as the exact time of 
the collection is noted on the source document and the CRF. Collection of samples more than 
10 hours after dose administration that are obtained ≤1 hour away from the nominal time 
relative to dosing will not be captured as a protocol deviation, as long as the exact time of the 
collection is noted on the source document and the CRF. This protocol deviation window 
does not apply to samples to be collected more than 10 hours after dose administration at 
outpatient/follow-up visits with visit windows.
Samples will be used to evaluate the PK of PF-06954522. Samples collected for analyses of 
PF-06954522 plasma concentration may also be used to evaluate safety or efficacy aspects 
related to concerns arising during or after the study, for metabolite identification and/or 
evaluation of the bioanalytical method, or for other internal exploratory purposes. The 
exploratory results may not be reported in the CSR.
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 4
Ge netic a nal ys es will n ot be perf or me d o n t hese P K plas ma sa m ples u nless c o nse nt f or t his 
was i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y  will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F -0 6 9 5 4 5 2 2 will be 
a nal yz e d usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h a p plica ble S O Ps. P ote ntial 
meta b olites ma y  be a nalyze d wit h eit her vali date d or e x pl orat or y met h o ds.
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y  de viati o ns fr o m t he P K sa m ple 
ha n dli n g pr oce d ure ( e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple 
inte grit y has bee n c o m pr o mise d.
Dr u g c o nce ntrati o n i nf or mati o n t hat ma y  u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gator sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt . T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
S pecifie d g e netic a nal ys es are n ot e val uate d i n t his st u d y .
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
A 4- m L  bl o o d sa m ple o pti mize d f or D N A is olati o n Pre p D 1 will be c ollecte d acc or di n g t o 
t he S o A , as l ocal re g ulati o ns a n d IR Bs/ E C s all o w.
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n(s). 
Ge nes a n d ot her a nal y tes (e g, pr otei ns, R N A, n o n dr u g meta b olites) ma y  be st u die d usi n g t he 
retai ne d sa m ples. 
See A p pe n di x 5 f or inf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n i n t he la b ma n ual a n d ot her 
s u p p orti n g d oc u me ntati o n.
8. 7. Bi o m ar kers
8. 7. 1. Pl as m a f or Me as ure me nt of 
Bl o o d sa m ples of a p pr o xi matel y  2 m L , t o pr o vi de a mi ni m u m of a p pr o xi matel y 0. 8 m L
plas ma, will be c ollecte d i nt o a p pr o priately la bele d t u bes c o ntai ni n g K 2E D T A f or
meas ure me nt of plas ma c o nce ntrati o ns of 
 at ti mes s pecifie d i n t he S o A . These sa m ples 
will be a nal yz e d at t he discreti o n of t he s p o ns or. If a nalys is of t he 
 sa m ples is j u d ge d t o 
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 5
be usef ul, sa m ples fr o m t he hi g hest d oses ma y  be a nalyz e d first a n d, if n o mea ni n gf ul effect 
of P F -0 6 9 5 4 5 2 2 is o bser ve d, sa m ples fr o m l o wer d ose gr o u ps ma y  n ot be assa ye d.
I nstr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he 
la b orat or y ma n ual or b y t he s p o ns or. T he act ual ti mes ma y c ha n ge b ut t he act ual date a n d 
ti me ( 2 4-h o ur cl oc k ti me) of eac h sa m ple will be rec or de d .
All eff orts will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g.
C ollecti o n of sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are
o btai ne d wit hi n 1 0 % of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n utes of a 
6 0- mi n ute sa m ple) will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of 
t he c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 
1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y fr o m t he n o mi nal ti me 
relati ve t o d osi n g will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he 
c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F.
Sa m ples c ollecte d f or a nal yses of 
plas ma c o nce ntrati o n ma y als o be use d t o e val uate 
safety or efficac y as pect s relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y, f or meta b olite 
i de ntificati o n a n d/ or e val uati o n of t he bi oa nalyt ical met h o d, or f or ot her i nter nal e x pl orat or y 
p ur p oses. T he e x pl orat or y res ults ma y  n ot be re p orte d i n t he C S R.
Ge netic a nal ys es will n ot be perf or me d o n t hese plas ma sa m ples u nless c o nse nt f or t his was 
i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of 
 will be a nalyz e d usi n g 
a vali date d a nal ytical met h o d i n c o m plia nce wit h a p plica ble S O Ps.
T he 
sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y de viati o ns fr o m t he sa m ple ha n dli n g 
pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d.
c o nce ntrati o n i nf or mati o n t hat ma y u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gat or sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 7. 2. Ret ai ne d Rese arc h S a m ples f or Bi o m ar kers
T hese Retai ne d Researc h Sa m ples will be c ollecte d i n t his st u d y :
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI
C CI


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!
A 2 mL whole blood Prep B2.5 optimized for serum as outlined in the SoA.
Retained Research Samples will be collected as local regulations and IRB/ECs allow 
according to the SoA. 
Retained Research Samples may be used for research related to the study intervention(s).
Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be studied using the 
retained samples. 
See Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in in the lab manual and other 
supporting documentation. 
8.8. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypothesis
No formal statistical hypothesis testing will be performed in this study.
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis 
Set
Description
Enrolled 
“Enrolled” means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process and 
randomization to study intervention. 
Safety analysis set
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Participants will 
be analyzed according to the product they actually received.
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Participant Analysis 
Set
Description
PK Concentration Set
All participants randomly assigned to study intervention and 
who receive at least 1 dose of study intervention and in whom 
at least 1 plasma concentration value is reported.
PK Parameter Set
All participants randomly assigned to study intervention and 
who receive at least 1 dose of study intervention and have at 
least 1 of the PK parameters of interest calculated.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data.
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.3.1. Safety Analyses
All safety analyses will be performed on the safety population (safety analysis set).
AEs, ECGs, BP, pulse rate, respiratory rate, temperature, 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, pulse rate, 
respiratory rate and temperature abnormalities of potential clinical concern will be described. 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study, will be considered source data and will 
not be required to be reported, unless otherwise noted. However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted. Demographic data collected at screening will be reported.
9.3.1.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters HR, QT interval, QTcF, PR interval, and 
QRS complex will be summarized by treatment and time. The frequency of uncorrected QT 
values above 500 ms will be tabulated.
The number (%) of participants with maximum post-dose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Safety QTcF Assessment
Degree of Prolongation
Mild (ms)
Moderate (ms)
Severe (ms)
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Absolute value
>450‑480
>480‑500
>500
Increase from baseline
30‑60
>60
If 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 time point. If any of the 3 individual ECG tracings has a QTcF value 
>500 ms, but the mean of the triplicates is not >500 ms, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500 ms value in appropriate clinical context. However, values from individual tracings 
within triplicate measurements that are >500 ms will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 ms. Changes from 
baseline will be defined as the change between the postdose QTcF value and the average of 
the pre-dose triplicate values at -1, -0.5, and 0 hours pre-dose on Day 1.
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. The results of such analyses may not be included in the CSR.
9.3.2. PK Analysis
The PK concentration and parameter populations are defined in Section 9.2.
9.3.2.1. Derivation of PF-06954522 PK Parameters
The plasma PK parameters for PF-06954522, following oral dose administration, will be 
derived from the plasma concentration-time profiles using standard noncompartmental 
methods as detailed in Table 4, as data permit. Actual PK sampling times will be used in the 
derivation of PK parameters. If actual PK sampling times are not available, nominal PK 
sampling times will be used in the derivation of PK parameters.
Table 4.
Plasma PF-06954522 PK Parameters
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 plasma concentration
Observed directly from data
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence
t½ *
Terminal elimination half-life
Loge(2)/kel, where kel is the terminal phase rate 
constant calculated by a linear regression of the 
log-linear concentration-time curve. Only those 
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Table 4.
Plasma PF-06954522 PK Parameters
Parameter
Definition
Method of Determination
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)
AUClast(dn)
Dose-normalized AUClast
AUClast/Dose
AUCinf(dn)*
Dose-normalized AUCinf
AUCinf/Dose
Cmax(dn)
Dose-normalized Cmax
Cmax/Dose
* As data permits.
9.3.2.2. Statistical Methods for PK Data
Plasma concentrations of PF-06954522 will be listed and summarized descriptively by dose 
(and fasting condition and ethnicity, if appropriate) and nominal PK sampling time. 
Individual participant and median profiles of the plasma concentration-time data will be 
plotted by dose (and fasting condition and ethnicity, if appropriate) using actual (for 
individual) and nominal (for median) times respectively. Median profiles will be presented 
on both linear and semi-log scales.
The plasma PK parameters will be summarized descriptively by dose (and fasting condition 
and ethnicity, if appropriate) as applicable. Dose-normalized AUCinf, AUClast, and Cmax will 
be plotted against dose (and fasting condition and ethnicity, if appropriate) using box and
whisker plots and will include individual participant values and the geometric means for each 
dose. These plots will be used to understand the relationship between PK parameters and 
dose (and fasting condition and ethnicity, if appropriate).
If the food effect is assessed, a mixed effects ANOVA will be performed separately on the 
natural log transformed AUCinf, AUClast, and Cmax (dose-normalized prior to analysis, if 
appropriate) with fasting condition included as a fixed effect and participant as a random 
effect. Further details of this analysis will be provided in the SAP.
Additional PK analyses may be performed if deemed appropriate and may not be included in 
the CSR.
9.3.3. Tertiary/Exploratory Endpoint(s) Analysis
The analysis of tertiary/exploratory endpoints will be detailed in the SAP.
9.3.4. Other Analyses 
Pharmacogenomic or biomarker data from Retained Research Samples may be collected 
during or after the trial and retained for future analyses; the results of such analyses are not 
planned to be included in the CSR.
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9.4. Interim Analyses
No formal interim analysis will be conducted for this study.
9.5. Sample Size Determination
A sufficient number of participants will be screened to achieve approximately 24 participants 
(up to 3 cohorts of up to approximately 10, 8 and 6 participants in Cohorts 1, 2, and 3, 
respectively) randomized. This sample size of approximately 24 participants for the entire 
study 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, tolerability, and PK 
assessment at each dose level.
In each period of Cohort 1, approximately 8 participants are planned to receive 
PF-06954522, and 2 participants are planned to receive placebo; with all participants in
Cohort 1 at the end of the study having received up to 5 doses of PF-06954522 and up to 
2 doses of placebo.
In each period of Cohort 2, approximately 6 participants are planned to receive
PF-06954522, and 2 participants are planned to receive placebo; with all participants in 
Cohort 2 at the end of the study having received up to 4 doses of PF-06954522 and up to 
2 doses of placebo.
An optional cohort of Japanese participants (Cohort 3) with a target sample size of 
approximately 6 participants (approximately 4 receiving PF-06954522, approximately 2 
receiving placebo in each period) may also be enrolled, if feasible. The actual number of 
Japanese participants may be adjusted based on emerging data or operational factors, with a 
maximum sample size of up to 8 participants (6 receiving PF-06954522 and 2 receiving
placebo in each period). 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
!
Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;
!
Applicable ICH-GCP guidelines;
!
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:
!
Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;
!
Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;
!
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH-GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies, European Medical Device Regulation 2017/745 for 
clinical device research, and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Not applicable.
10.1.3. Informed Consent Process
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions regarding the 
study. The participant should be given sufficient time and opportunity to ask questions and to 
decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each participant is fully informed about the nature and 
objectives of the study, the sharing of data related to the study, and possible risks associated 
with participation, including the risks associated with the processing of the participant’s 
personal data. 
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about their
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened are required to sign a new ICD.
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10.1.3.1. Electronic Consent 
Participants may be able to experience the informed consent process by electronic means 
(eConsent). The eConsent process includes an electronic presentation of the informed 
consent document (eICD), clinical trial educational components (as applicable), and 
electronic signatures (if allowed by local regulations). The use of eConsent does not replace 
or alter the ICD content or informed consent process as described above. The eConsent 
process complies with applicable regulations and sponsor policies to ensure reliability and 
data privacy. 
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains SOPs on how to respond in the event of unauthorized access, use, or 
disclosure of sponsor information or systems.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will not use an E-DMC.
10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
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www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized.
Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
18 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
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10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source records and documents.
This verification may also occur after study completion. It is important that the 
investigator(s) and their relevant personnel are available during the monitoring visits and 
possible audits or inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and IQMP
maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
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provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes a source document and its origin can be found in the Source 
Document Locator, which is maintained by the sponsor’s designee (Pfizer CRU).
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor’s designee (Pfizer CRU).
The investigator must maintain accurate documentation (source record) that supports the 
information entered in the CRF.
The sponsor or designee will perform monitoring to confirm that data entered into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. Use of Medical Records
There may be instances when copies of medical records for certain cases are requested by 
Pfizer Safety, where ethically and scientifically justified and permitted by local regulations, 
to ensure participant safety.
Due to the potential for a participant to be re-identified from their medical records, the 
following actions must be taken when medical records are sent to the sponsor or sponsor 
designee:
!
The investigator or site staff must redact personal information from the medical 
record. The personal information includes, but is not limited to, the following: 
participant names or initials, participant dates (eg, birth date, date of hospital 
admission/discharge, date of death), participant identification numbers (eg, Social 
Security number, health insurance number, medical record number, 
hospital/institution identifier), participant location information (eg, street address, 
city, country, postal code, IP address), participant contact information (eg, 
telephone/fax number, email address).
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!
Each medical record must be transmitted to the sponsor or sponsor designee using 
systems with technical and organizational security measures to ensure the protection 
of personal data (eg, Florence is the preferred system if available). 
There may be unplanned situations where the sponsor may request medical records (eg, 
sharing medical records so that the sponsor can provide study-related advice to the 
investigator). The medical records should be submitted according to the procedure described 
above.
10.1.10. Study and Site Start and Closure
The study start date is the date of the first participant’s first visit.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
!
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor’s procedures, or the ICH-GCP 
guidelines;
!
Inadequate recruitment of participants by the investigator;
!
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.11. Publication Policy
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
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preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study.
Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section.
The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. If any patent action is required to protect intellectual property rights, the 
investigator agrees to delay the disclosure for a period not to exceed an additional 60 days 
upon request from Pfizer. This allows Pfizer to protect proprietary information and to provide 
comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study-intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
study results. For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication.
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.12. Sponsor’s Medically Qualified Individual
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the clinical trial management system.
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from non-study healthcare professionals, participants are provided 
with an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol 
and study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week.
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. 
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values; for example: calculation of estimated kidney function (ie, 2021 
CKD-EPI eGFR as standard lab safety test). These additional tests would not require 
additional collection of blood. Unscheduled clinical laboratory measurements may be 
obtained at any time during the study to assess any perceived safety issues.
Table 5.
Protocol -Required Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV, MCH, MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN
Creatinine
Cystatin Ca
eGFRb
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Direct and indirect bilirubinc
GGT
Alkaline phosphatase
Creatine Kinase (CK)
Uric acid
Albumin
Total protein
Local dipstickg:
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Laboratory:
Microscopy and 
cultured
FSHe,f
HBcAbf
HBsAbf
HBsAgf
HCVAbf
HIVf
HbA1cf
TSHf
Urine albumin to creatinine 
ratio (quantitative)f,h
Urine drug screeni
Calcitoninj
Amylasej
Lipasej
Total bile acidsj
a.
Serum Cystatin C (Scys): Screening or Baseline Scys is recommended to help differentiate post-baseline DIKI from 
DICI. Post-baseline, Scys is measured if and only if serum creatinine increase is observed (see Section 7.1.1).
b.
Screening and Baseline eGFR is measured with Screat-based formula. Age-specific kidney function calculation (see 
Section 10.7.2) is recommended to assess presence or absence of post-baseline change in kidney function.
c.
Test as reflex if total bilirubin is elevated.
d.
Only if UTI is suspected and urine dipstick is positive for nitrites or leukocyte esterase or both.
e.
For confirmation of postmenopausal status only in females <60 years old and not using hormonal or HRT only.
f.
At screening only.
g.
Assessed by urine dipstick.
h.
Assessed by urine sample biochemical analysis.
i.
At screening and upon admission for each inpatient stay. The minimum requirement for drug screening includes 
cocaine, THC, opiates/opioids, benzodiazepines, and amphetamines (others are site- and study-specific).
j.
Review of these data is not required prior to dosing and dose escalation in each period; cumulative results will be 
reviewed as they become available.
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Table 6.
Protocol-Required Laboratory Assessments – Reflex Testing
Hematology
Chemistry
Urinalysis on Site
Other
If Hb/RBC abnormal: 
MCV, MCH, MCHC 
Neutrophils (%) 
Eosinophils (%) 
Basophils (%) 
Lymphocytes (%) 
Monocytes (%) 
RBC morphology 
RBC distribution width
Required:
For suspected DILI:
AST/ALT 
T bili, albumin, CK, direct 
and indirect bili 
GGT, PT/INR, eosinophils 
(%), alkaline phosphatase
The following additional 
testing may be warranted:
Acetaminophen/paracetam
ol or 
protein adduct levels 
Hepatitis serology (even if 
screening negative) 
Total bile acids
Liver imaging
For suspected DICI/DIKI: 
Creatinine (Screat)
Cystatin Ca (Scys)
eGFR (Screat only and 
combined Screat+Scys)b
Urine albumin-to-
creatinine-ratio (UACR) 
Local Laboratory
Microscopy and 
culture for positive 
local dipstick testsc
Hepatitis B DNA 
Hepatitis C RNA
a.
Cystatin C (Scys): Screening or Baseline Scys is recommended to help differentiate post-baseline DIKI from 
DICI. Post-baseline, Scys is measured if and only if clinically-relevant serum creatinine increase post-baseline is
observed (see Section 7.1.1).
b.
Creatinine (Screat): Screening and Baseline eGFR is measured with Screat-based formula. Age-specific kidney 
function calculation (see Section 10.7.2) is recommended to assess the presence or absence of post-baseline 
change in kidney function.
c.
Only if UTI is suspected and urine dipstick is positive for nitrites or leukocyte esterase or both. Any positive 
results are to be reported as an AE.
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.
Laboratory/analyte results that could unblind the study and have been collected for the 
purpose of the study will not be reported to investigator sites or other blinded personnel until 
the study has been unblinded.
Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained and 
stored for the duration of the study. Upon completion of the study, these retained safety 
samples may be used for the assessment of exploratory safety biomarkers 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.
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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
All AEs/SAEs associated 
with EDP or EDB
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)**
Environmental or 
occupational exposure 
to the product under 
study to a 
nonparticipant (not 
involving EDP or EDB)
None. Exposure to a study 
non-participant is not 
collected on the CRF
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported***
*
EDP (with or without an associated SAE): is reported to Pfizer Safety using the CT SAE Report 
Form and EDP Supplemental Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form, which would also include 
details of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 
!
When an AE or SAE occurs, it is the responsibility of the investigator to review 
all documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.
!
The investigator will then record all relevant AE or SAE information in the CRF.
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10.4. Appendix 4: Contraceptive and Barrier Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 
!
Refrain from donating sperm.
PLUS either:
!
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
!
Must agree to use contraception/barrier as detailed below:
!
Agree to use a male condom, and should also be advised of the benefit for 
a female partner to use a highly effective method of contraception, as a 
condom may break or leak when having sexual intercourse with a 
WOCBP who is not currently pregnant.
!
In addition to male condom use, a highly effective method of 
contraception may be considered in WOCBP partners of male participants 
(refer to the list of highly effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of Inclusion Criterion 1 (Age and Sex; Section 5.1) and specify 
the reproductive requirements for including female participants. Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
!
A female participant is eligible to participate if she (a) is not pregnant or 
breastfeeding; and (b) agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction for at least 28 days after last dose of study intervention; and (c) Is not a 
WOCBP (see definition in Section 10.4.3).
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 or oligomenorrhea) and a menstrual cycle cannot be 
confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenarchal.
2. Premenopausal female with 1 of the following:
!
Documented hysterectomy;
!
Documented bilateral salpingectomy;
!
Documented bilateral oophorectomy.
For individuals with permanent infertility due to a medical cause other than the above
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be applied 
to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
3. Postmenopausal female.
!
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition:
!
A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 
!
A female on HRT and whose menopausal status is in doubt will be required to 
use one of the highly effective nonestrogen hormonal contraception methods 
if she wishes to continue her HRT during the study. Otherwise, she must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
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10.4.4. Contraception Methods
Contraceptive use by male participants or their female partners who are of childbearing 
potential should be consistent with local availability/regulations regarding the use of 
contraceptive methods for those participating in clinical trials.
The following contraceptive methods for male participants or their female partners who are 
of childbearing potential are appropriate for this study:
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner.
!
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:
!
Oral + barrier*
!
Intravaginal + barrier*
!
Transdermal + barrier*
7. Progestogen-only hormone contraception associated with inhibition of ovulation:
!
Oral + barrier*
!
Injectable + barrier*
8. Sexual Abstinence
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
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with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
* Acceptable barrier methods to be used concomitantly with options 6 or 7 for the study 
include any of the following:
!
Male or female condom with or without spermicide;
!
Cervical cap, diaphragm, or sponge with spermicide;
!
A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods).
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10.5. Appendix 5: 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, a blood sample 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 study intervention 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:
!
Retained samples 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 Retained 
Research Samples 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.
!
Samples for genetic research will be labeled with a code. The key between the code 
and the participant’s personally identifying information (eg, name, address) will be 
held securely at the study site.
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be 
elevated within the same laboratory sample). In rare instances, by the time T bili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST or ALT in addition to T bili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:
!
Participants with AST/ALT and T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili value ≥2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.
!
For participants with baseline AST OR ALT OR T bili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
!
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values ≥2 times the baseline values AND ≥3 × ULN; or ≥8 × ULN (whichever is 
smaller).
!
Preexisting values of T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller).
Rises in AST/ALT and T bili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
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The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, eosinophils (%), and alkaline phosphatase. Consideration should also be 
given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology. A detailed history, including relevant information, 
such as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, total bile acids, liver imaging (eg, biliary tract), and 
collection of serum samples for acetaminophen/paracetamol drug and/or protein adduct 
levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.7. Appendix 7: Kidney Safety: Monitoring Guidelines
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline Screat 
measurement to estimate kidney function [eg, Screat-based eGFR]. Obtaining Screening or 
Baseline Scys and postbaseline reflex Scys (if confirmed Screat increase ≥0.3 mg/dL) makes 
it feasible to distinguish AKI from DICI. If Screat increase is confirmed after baseline, then 
reflex measurement of Scys is indicated:
ADULTS: Currently, 2021 CKD-EPI eGFR equations (Screat only-based and combined 
Screat plus Scys-based) are valid for use in adults only. At baseline Screat and Scys values 
are needed to calculate 2021 CKD-EPI eGFR by Screat only-based equation (see Section 
10.7.2.1) and by combined Screat plus Scys-based equation. When post-baseline Screat 
increase ≥0.3 mg/dL is confirmed, then reflex Scys measurement is needed to enable 
post-baseline comparison of eGFR changes (Screat only-based eGFR and combined Screat 
plus Scys eGFR). 
10.7.2. Age-Specific Kidney Function Calculation Recommendations
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
eGFR (mL/min/1.73m²)[17]
2021 CKD-
EPI            
Screat Only
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤ 0.7
NA
eGFR = 143 × (Screat/0.7)-0.241  ×  (0.9938)Age
Female
if > 0.7
NA
eGFR = 143 × (Screat/0.7)-1.200  ×  (0.9938)Age
Male
if ≤ 0.9
NA
eGFR = 142 × (Screat/0.9)-0.302  ×  (0.9938)Age
Male
if > 0.9
NA
eGFR = 142 × (Screat/0.9)-1.200  ×  (0.9938)Age
2021 CKD-
EPI           
Screat-Scys 
Combined
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤ 0.7
if ≤ 0.8
eGFR = 130 × (Screat/0.7)-0.219  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if ≤ 0.7
if > 0.8
eGFR = 130 × (Screat/0.7)-0.219  × (Scys/0.8)-0.778  × (0.9961)Age
Female
if > 0.7
if ≤ 0.8
eGFR = 130 × (Screat/0.7)-0.544  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if > 0.7
if > 0.8
eGFR = 130 × (Screat/0.7)-0.544  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if ≤ 0.9
if ≤ 0.8
eGFR = 135 × (Screat/0.9)-0.144  × (Scys/0.8)-0.323  × (0.9961)Age
Male
if ≤ 0.9
if > 0.8
eGFR = 135 × (Screat/0.9)-0.144  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if > 0.9
if ≤ 0.8
eGFR = 135 × (Screat/0.9)-0.544  ×  (Scys/0.8)-0.323  × (0.9961)Age
Male
if > 0.9
if > 0.8
eGFR = 135 × (Screat/0.9)-0.544  ×  (Scys/0.8)-0.778  × (0.9961)Age
10.7.3. Kidney Function Calculation Tools
The sponsor has provided the following resources to investigational sites when required to 
calculate age-specific kidney function at Screening, Baseline, and post-Baseline visits. Site 
calculations of kidney function can be performed manually, using the age appropriate 
formulae (see Section 10.7.2) and can use recommended online kidney function calculators 
to reduce the likelihood of a calculation error. 
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The United States National Kidney Foundation Online Calculators. 
!
Adults (18 years and above) - 2021 CKD-EPI Creatinine Online Calculator (eGFR): 
https://www.kidney.org/professionals/KDOQI/gfr_calculator
Investigational sites are responsible to ensure that the accurate age-specific equation is 
selected and that the correct units for serum creatinine (mg/dL only), serum cystatin C (mg/L 
only), total body weight (kg only), and age (years). Investigators are expected to (i) review 
and confirm correctness of the kidney function calculation results and (ii) evaluate the 
calculated value within the context of historical information available to them in the 
participant’s medical record. Investigators are responsible for the clinical oversight of the 
participant eligibility process, kidney function calculation, and dose selection and 
adjustments per study protocol. Investigators are encouraged to direct questions or 
uncertainties regarding kidney function and dosing to the Pfizer Clinical Team and Medical 
Monitor, if needed.
10.7.4. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function will be according to CTCAE criteria.
CTCAE 
Term 
(2017)
Grade 1
Grade 2
Grade 3
Grade 4
Grade 
5
AKI
NA
NA
Hospitalization 
indicated
Life-threatening 
consequences; 
dialysis indicated
Death
AKI:  A disorder characterized by acute loss of kidney function (within 2 weeks) and is traditionally 
classified as pre-renal (low blood flow into kidneys), renal (kidney damage), or post-renal causes (ureteral or 
bladder outflow obstruction.
Creatinine 
increased
>ULN to 1.5 ×
ULN
>1.5 to 3.0 ×
baseline OR >1.5 
to 3.0 × ULN
>3.0 to 6.0 ×
baseline OR >3.0 
to 6.0 × ULN
>6.0 × ULN
NA
CKD
eGFR ≥60 to 
89 mL/min/1.73m² 
OR                 
eCrCl ≥60 to 80 
mL/min 
eGFR 30 to 
59 mL/min/1.73m² 
OR                  
eCrCl 30 to 59 
mL/min
eGFR 15 to 
29 mL/min/1.73m² 
OR                
eCrCl 15 to 29 
mL/min
eGFR 
<15 mL/min/1.73m² 
OR       
eCrCl <15 mL/min 
OR  
dialysis indicated
Death
Proteinuria
ADULTS: 
Proteinuria 1+ OR   
Proteinuria >0.5 to 
<1.0 g/24 h
ADULTS: 
Proteinuria 2+ or 
3+               OR        
Proteinuria 1.0 to 
<3.5 g/24 h
ADULTS: 
Proteinuria 4+          
OR                
Proteinuria ≥3.5 
g/24 h 
NA
NA
CKD: A disorder characterized by gradual and usually permanent loss of kidney function resulting in kidney 
failure.
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P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 9
1 0. 9. A p pe n di x 9 : Pr o hi bite d C o nc o mit a nt Me dic ati o ns T h at M a y Res ult i n D DI
T he pr o hi bite d c o nc o mita nt me dicati o ns liste d bel o w s h o ul d n ot be ta ke n wit h P F - 0 6 9 5 4 5 2 2
f or t he peri o d of ti me at least e q ual t o t he re q uire d was h o ut peri o d liste d i n t he ta ble, a n d 
t hr o u g h o ut t he c o n d uct of t he st u d y. 
T he Pfizer st u d y tea m is t o be n otifie d of a n y  pr o hi bite d me dicati o ns ta ke n d uri n g t he st u d y. 
After c o ns ulti n g wit h t he s p o ns or, t he i n vesti gat or will ma ke a j u d g me nt o n t he o n g oi n g 
partici pati o n of a n y partici pa nt wit h pr o hi bite d me dicati o n use d uri n g t he st u d y.
T his list of dr u gs pr o hi bite d f or p ote ntial D DI c o ncer ns wit h t he I M P ma y  be re vise d d uri n g 
t he c o urse of t he st u d y wit h writte n n otificati o n fr o m s p o ns or, t o i ncl u de or e xcl u de s pecific 
dr u gs or dr u g cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or t he I M P, 
a vaila bilit y of ne w i nf or mati o n i n literat ure o n t he D DI p ote ntial of ot her dr u gs), if t he 
o verall b e nefit:ris k assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y  i m pact 
t he safety of partici pa nts or t he scie ntific val ue of t he trial   
T his is n ot a n all -i ncl usi ve list. Site staff s h o ul d c o ns ult wit h t he s p o ns or or desi g nee wit h 
a n y q uestio ns re gar di n g p ote ntial D DI.
I n vesti gat ors s h o ul d c o ns ult t he pr o d uct la bel f or a n y ot her me dicati o n use d d uri n g t he st u d y 
f or i nf or mati o n re gar di n g me dicati o n t hat is pr o hi bite d f or c o nc o mita nt use. 
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 0
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 1
1 0. 1 0. A p pe n di x 1 0 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y be use d i n t he pr ot oc ol.
A b bre vi ati o n
Ter m
A 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verity sta n dar dizati o n)
A bs
a bs ol ute
A D L
acti vit y/ acti vities of d ail y li vi n g
A E
a d verse e ve nt
A E SI
a d verse e ve nt of s pecial i nterest
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A N O V A
a nal ys is of varia nce
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c o nce ntrati o n-ti me c ur ve
A U C 2 4
area u n der t he c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o 2 4 h o urs
A U C i nf
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nit y
A U C i nf( d n)
d ose -n or malize d A U C i nf
A U C last
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m 0 t o ti me of last 
meas ura ble c o nce ntrati o n
A U C last( d n)
d ose -n or malize d A U C last
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
B A
bi oa vaila bilit y
B B S
Bi os peci me n Ba n ki n g S yste m
B E
bi oe q ui vale nce
B MI
b o d y  mass i n de x
B P
bl o o d press ure
b p m
beats per mi n ute
B U N
bl o o d urea nitr o ge n
C eff
stea d y state efficaci o us c o nce ntrati o n
C F R
C o de of Fe deral Re g ulati o ns
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
C hr o nic K i d ne y D isease E pi de mi ol o g y C olla b orati o n
C L
t otal cleara nce of dr u g fr o m e g, plas ma
C L / F
a p pare nt cleara nce of dr u g fr o m e g, plas ma
C L p
plas ma cleara nce
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C ma x ( d n)
d ose -n or malize d C ma x
C O 2
car b o n di o xi de ( bicar b o nate)
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 2
A b bre vi ati o n
Ter m
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C R U
cli nical researc h u nit
C S R
C li nical S t u d y R e p ort
C T
cli nical trial
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C TI S
Cli nical Trial I nf or mati o n S y ste m
C V
cardi o vasc ular
D C T
data c ollecti o n t o ol
D DI
dr u g -dr u g i nteracti o n 
DI CI
dr u g -i n d uce d creati ni ne i ncrease
DI KI
dr u g -i n d uce d ki d ne y i nj ur y
DI LI
dr u g -i n d uce d li ver i nj ur y
D N A
de o x yri b o n ucleic aci d
D U
dis pe nsa ble u nit
E C
et hics c o m mittee
E C C
emer ge nc y  c o ntact car d
E C G
electr ocar di o gra m or electr ocar di o gra p h y
e Cr Cl
esti mate d creati ni ne cleara nce
e C R F
electr o nic case re p ort f or m
E D B
e x p os ure d uri n g breastfee di n g
E -D M C
E xter nal Data M o nit ori n g C o m mittee
E D P
e x p os ure d uri n g pre g na nc y
E D R
e xte m p ora ne o us dis pe nsi n g rec or d
e G F R
esti mate d gl o mer ular filtrati o n rate
E G F R
e pi der mal gr o wt h fact or rece pt or
eIC D
electr o nic i nf or me d c o nse nt d oc u me nt
E M A
E ur o pea n Me dici nes A ge nc y
E T
en d of treat me nt
e S A E
electr o nic seri o us a d verse e ve nt
E S R
er yt hr oc y te se di me ntati o n rate
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli ni cal Trials 
(E ur o pea n Cli nical Trials Data base )
F D A
F o o d a n d Dr u g A d mi nistrati o n
FI H
first i n h u ma n
F S H
f ollicle-sti m ulati n g h or m o ne
F/ U
f oll o w-u p
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 3
A b bre vi ati o n
Ter m
G 1 t o G 5
Gra de ( K DI G O e G F R cate g or y  sta n dar dizati o n)
G C P
G o o d Cli nical Practice
G G T
ga m ma -gl uta m y l tra nsferase
G L P -1
gl uca g o n -li ke pe pti de-1
G L P -1 R
gl uca g o n -li ke pe pti de-1 rece pt or
G L P -1 R A
gl uca g o n -li ke pe pti de-1 rece pt or a g o nist
H b A 1 c
gl yc ate d he m o gl o bi n
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C V A b
he patitis C a nti b o d y
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
In vesti gat or’s B r oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical 
Re q uire me nts f or P har mace uticals f or H u ma n Use
I D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal p r o d uct
I ND
In vesti gati o nal N e w D r u g 
I N R
i nter nati o nal n or malize d rati o
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I PM
i n vesti gati o nal pr o d uct ma n ual
I Q M P
i nte grate d q uality ma na ge me nt pla n
I RB
Instit uti o nal R e vie w B oar d
I R C
i nter nal re vie w c o m mittee
I R T
Interacti ve R es p o nse T ec h n ol o g y
I S O
I nter nati o nal Or ga nizati o n f or Sta n dar dizati o n
I V
I ntra ve n o us(ly)
I W R
Interacti ve We b R es p o nse
K
Pr o p orti o nalit y  c o nsta nt f or Sc h wartz E q uati o ns ( ki d ne y f u ncti o n)
K 2E D T A
di p otassi u m et h y le ne dia mi netetraacetic aci d
k el
first-or der eli mi nati o n rate c o nsta nt
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
L B B B
left b u n dle bra nc h bl oc k
L D H
lactate de hy d r o ge nase
L F T
li ver f u ncti o n test
L P D
l ocal pr o d uct d oc u me nt
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 4
A b bre vi ati o n
Ter m
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M E N 2
m ulti ple e n d ocri ne ne o plasia s y n dr o me t y pe 2
M QI
me dicall y  q ualifie d i n di vi d ual
M T C
me d ullar y  t h yr oi d carci n o ma
N A
n ot a p plica ble
N H P
n o n h u ma n pri mate
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o o bser ve d a d verse effect le vel
P b o
place b o
P C R
p ol y merase c hai n reacti o n
P C R U
Pfizer C li nical R esearc h U nit
P D
p har mac o d y n a mic(s)
P E
p h y sical e xa mi nati o n
P G x 
p har mac o ge n o mic(s)
PI
pri nci pal i n vesti gat or
PI B
p o w der i n b ottle
P K
p har mac o ki netic(s)
P S S A
Pfizer's Seri o us A d verse E ve nt S u b missi o n Assista nt
P T
pr ot hr o m bi n ti me
P T A
p ost -trial access
P T H
parat h or m o ne
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q D
o nce dail y
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
Q T L
q ualit y  tolera nce li mit
q ual
q ualitati ve
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
S A D E
seri o us a d verse de vice effect
S A E
seri o us a d verse e ve nt
S A P
S tatistical A nal y sis P la n
S C
s u bc uta ne o us
S C L
s u p pl y c hai n lea d
S cr
ser u m creati ni ne
Screat
ser u m creati ni ne 
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI
C CI
C CI
C CI


P F -0 6 9 5 4 5 2 2
Pr ot oc ol C 4 0 0 1 0 0 1
Fi nal Pr ot oc ol, 1 7 J ul y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol T e m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 5
A b bre vi ati o n
Ter m
Sc y s
ser u m c ystati n C
S o A
sc he d ule of acti vities
S O P
sta n dar d o perati n g pr oce d ure
S R S D
S i n gle R efere nce S afet y D oc u me nt
S U S A R
S us pecte d U ne x pecte d S eri o us A d verse R eacti o n
t½
ter mi nal p hase half-life
T 2 D M
t ype 2 dia betes mellit us
T 3
t otal trii o d ot h yr o ni ne
T 4
t h yr o xi ne
T B
t u berc ul osis 
T B D
t o be deter mi ne d
T b ili
t otal bilir u bi n
T ma x
Ti m e f or C ma x
T H C
tetra hy dr oca n na bi n ol
T O C
ta ble of c o nte nts
T S H
t h yr oi d-sti m ulati n g h or m o ne
U A C R
u ri ne al b u mi n/creati ni ne rati o
U L N
u p per li mit of n or mal
U S
U nite d States
U S PI
U nite d States Prescri bi n g I nf or mati o n
U TI
uri nar y  tract i nfecti o n
V ss
stea d y-state v ol u me of distri b uti o n
V z/ F
a p pare nt v ol u me of distri b uti o n f or e xtra vasc ular d osi n g
W B C
w hite bl o o d cell
W O C B P
w o ma n / w o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9 e 0f 3 af c\ A p pr o v e d\ A p pr o v e d O n: 1 9- J ul- 2 0 2 3 0 1: 5 5 ( G M T)
C CI


PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 106
11. REFERENCES
1.
Orskov C, Holst JJ, Knuhtsen S, et al. Glucagon-like peptides GLP-1 and GLP-2, 
predicted products of the glucagon gene, are secreted separately from pig small 
intestine but not pancreas. Endocrinology. 1986;119(4):1467-75.
2.
Kreymann B, Williams G, Ghatei MA, et al. Glucagon-like peptide-1 7-36: a 
physiological incretin in man. Lancet. 1987;2(8571):1300-4.
3.
Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of 
gastric emptying outweighs its insulinotropic effects in healthy humans. Am J 
Physiol. 1997;273(5):E981-8.
4.
Flint A, Raben A, Astrup A, et al. Glucagon-like peptide 1 promotes satiety and 
suppresses energy intake in humans. J Clin Invest. 1998;101(3):515-20.
5.
Federation ID. IDF Diabetes Atlas. Available from: 
https://diabetesatlas.org/atlas/tenth-edition/. Accessed on: 19 Jun.
6.
Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 
2011;34(6):1249-57.
7.
Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new 
paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773-95.
8.
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular 
and microvascular complications of type 2 diabetes (UKPDS 35): prospective 
observational study. BMJ. 2000;321(7258):405-12.
9.
Nauck MA, Quast DR, Wefers J, et al. GLP-1 receptor agonists in the treatment of 
type 2 diabetes - state-of-the-art. Mol Metab. 2021;46:101102.
10.
Ozempic (semaglutide). US Prescribing Information (USPI). Plainsboro, NJ: Novo 
Nordisk Inc; 2017. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf. Accessed: 
16 Jun 2023.
11.
Victoza (liraglutide) US Prescribing Information (USPI). Plainsboro, NJ. Novo 
Nordisk Inc; 2017. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022341s027lbl.pdf. 
Accessed: 16 Jun 2023.
12.
Rybelsus (semaglutide) US Prescribing Information (USPI). Plainsboro, NJ. Novo 
Nordisk Inc; 2022. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213051s011lbl.pdf. 
Accessed: 16 Jun 2023.
13.
Victoza (liralutide) USPI. U.S. Food and Drug Administration website. Available 
from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022341s031lbl.pdf. 
Accessed: 06 Jun 2023.
14.
Pratt E, Ma X, Liu R, et al. Orforglipron (LY3502970), a novel, oral non-peptide 
glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-
controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. 
Diabetes Obes Metab. 2023;10.1111/dom.15150.
15.
Saxena AR, Frias JP, Brown LS, et al. Efficacy and Safety of Oral Small Molecule 
Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control 
090177e19e0f3afc\Approved\Approved On: 19-Jul-2023 01:55 (GMT)


PF-06954522
Protocol C4001001
Final Protocol, 17 July 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (14 April 2023)
Page 107
Among Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Netw 
Open. 2023;6(5):e2314493.
16.
Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 
U.S. Department of Health and Human Services. Food and Drug Administration. July 
2009. Available from: https://www.fda.gov/media/116737/download. Accessed on: 
28 Jun 2023.
17.
Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based 
Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-49.
090177e19e0f3afc\Approved\Approved On: 19-Jul-2023 01:55 (GMT)

SAP_001.pdf: 
Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
PFIZER  CONFIDENTIAL  
TMF Doc ID: 98.03 
Page 1 of 27 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol C4001001 
 
 
 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-
CONTROLLED, CROSSOVER, FIRST-IN-HUMAN STUDY TO ASSESS THE 
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE 
ASCENDING ORAL DOSES OF PF-06954522 IN HEALTHY ADULT 
PARTICIPANTS 
 
 
 
Statistical Analysis Plan  
(SAP) 
 
 
 
 
 
 
 
Version: 
1   
 
Date:  
14 Sept 2023   
090177e19ea48cd2\Final\Final On: 20-Sep-2023 22:12 (GMT)


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 of 2 7  
T A B L E O F C O N T E N T S  
LI S T O F T A B L E S  ................................................................................................................ 4 
LI S T O F FI G U R E S  ............................................................................................................... 4 
A P P E N DI C E S  ...................................................................................................................... 4 
1. V E R SI O N HI S T O R Y ........................................................................................................ 5 
2. I N T R O D U C TI O N  ............................................................................................................. 5 
2. 1. M o dificati o ns t o t he A nal ysis Pla n Descri be d i n t he Pr ot oc ol  ................................ 5 
2. 2. St u d y O bjecti ves, E n d p oi nts, a n d Esti ma n ds  ......................................................... 5 
2. 3. St u d y Desi g n  ......................................................................................................... 6 
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S  .............................................................................................................. 7 
3. 1. Pri mar y E n d p oi nt(s)  .............................................................................................. 7 
3. 1. 1. A d verse E ve nts  ......................................................................................... 8 
3. 1. 2. Cli nical Saf et y La b orat or y Data  ................................................................ 8 
3. 1. 3. Vital Si g ns  ................................................................................................ 8 
3. 1. 4. C o nti n u o us Car diac M o nit ori n g  ................................................................ 9 
3. 1 . 5. Electr ocar di o gr a ms.................................................................................... 9 
3. 1. 6. P h ysical E xa mi nati o ns  ............................................................................ 1 0 
3. 2. Sec o n dar y E n d p oi nt(s)  ........................................................................................ 1 0 
3. 3. Ot her E n d p oi nt(s)  ................................................................................................ 1 1 
3. 3. 1. A d diti o nal Plas ma P F -0 6 9 5 4 5 2 2 P K Para meters  ..................................... 1 1 
3. 3. 2. Plas ma P F -0 6 9 5 4 5 2 2 P K Para meters D uri n g F o o d Effect Peri o d (if 
c o n d ucte d) .................................................................................................... 1 2 
 .................................................. 1 2 
3. 3. 4. Saf et y S u m maries a n d P K Para meters D uri n g Ja pa nese C o h ort (if 
c o n d ucte d) .................................................................................................... 1 2 
3. 4. Baseli ne Varia bles  ............................................................................................... 1 2 
3. 5. Saf et y E n d p oi nts  ................................................................................................. 1 2 
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S)  ................................................. 1 3 
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S  ................................................. 1 4 
5. 1. H y p ot heses a n d Decisi o n R ules  ........................................................................... 1 4 
5. 2. Ge ner al Met h o ds  ................................................................................................. 1 4 
5. 2. 1. A nal yses f or C o nti n u o us E n d p oi nts  ......................................................... 1 4 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 of 2 7  
5. 2. 2. A nal yses f or Cate g orical E n d p oi nts  ......................................................... 1 4 
5. 2. 3. Mi xe d Eff ects M o del  ............................................................................... 1 4 
5. 3. Met h o ds t o Ma na ge Missi n g Data  ....................................................................... 1 5 
5. 3. 1. C o nce ntr ati o ns Bel o w t he Li mit of Q ua ntificati o n  ................................... 1 5 
5. 3. 2. De viati o ns, Missi n g C o nce ntrati o ns a n d A n o mal o us Val ues .................... 1 5 
5 . 3. 3. Plas ma P har mac o ki netic Para meters ........................................................ 1 6 
6. A N A L Y S E S A N D S U M M A RI E S  ................................................................................... 1 6 
6. 1. Pri mar y E n d p oi nt(s)  ............................................................................................ 1 6 
6 . 1. 1. A d verse E ve nts  ....................................................................................... 1 6 
6. 1. 2. Cli nical Saf et y La b orat or y Data  .............................................................. 1 7 
6. 1. 3. Vital Si g ns  .............................................................................................. 1 7 
6. 1. 4. C o nti n u o us Car diac M o nit ori n g  .............................................................. 1 8 
6. 1. 5. Electr ocar di o gr a ms .................................................................................. 1 8 
6. 1. 6. P h ysical E xa mi nati o ns  ............................................................................ 1 9 
6. 2. Sec o n dar y E n d p oi nt(s)  ........................................................................................ 1 9 
6. 3. Ot her E n d p oi nt(s)  ................................................................................................ 2 0 
6. 3. 1. A d diti o nal Plas ma P F -0 6 9 5 4 5 2 2 P K Para meters  ..................................... 2 0 
6. 3. 2. Plas ma P F -0 6 9 5 4 5 2 2 P K Para meters D uri n g F o o d Effect Peri o d (if 
c o n d ucte d) .................................................................................................... 2 1 
 .................................................. 2 1 
6. 3. 4. Saf et y S u m maries a n d P K Para meters D uri n g Ja pa nese C o h ort (if 
c o n d ucte d) .................................................................................................... 2 2 
6. 3. 5. Ba n ke d Bi os peci me ns  ............................................................................. 2 2 
6. 4. S u bset A nal yses  .................................................................................................. 2 2 
6. 5. Baseli ne a n d Ot her S u m maries a n d A nal y ses ...................................................... 2 2 
6. 5. 1. Baseli ne S u m maries  ................................................................................ 2 2 
6. 5. 2. St u d y C o n d uct a n d Partici pa nt Dis p ositi o n  .............................................. 2 2 
6. 5. 3. St u d y Tr eat me nt E x p os ure  ...................................................................... 2 2 
6. 5. 4. C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts  ................................ 2 3 
6. 6. Saf et y S u m maries a n d A nal yses  .......................................................................... 2 3 
7. I N T E RI M A N A L Y S E S  ................................................................................................... 2 3 
7. 1. I ntr o d ucti o n  ......................................................................................................... 2 3 
7. 2. I nteri m A nal yses a n d S u m maries ......................................................................... 2 3 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 of 2 7  
8. R E F E R E N C E S  ................................................................................................................ 2 3 
A P P E N DI C E S  .................................................................................................................... 2 4 
 
LI S T O F T A B L E S  
T a ble  1. 
S u m mar y of C ha n ges  .............................................................................. 5 
T a ble 2. S u m mar y of P F -0 6 9 5 4 5 2 2 plas ma P K para meters t o be calc ulate d. ........................ 1 1 
T a ble 3. A d diti o nal P F -0 6 9 5 4 5 2 2 Plas ma P K Para meters  .................................................... 1 2 
 ............................................ 1 2 
T a ble 5. S u m mar y Statistics f or P F - 0 6 9 5 4 5 2 2 Plas ma P K Para meters  ................................. 1 9 
T a ble 6.  
S u m mar y statistics t o be pr o d uce d f or a d diti o nal plas ma P K 
Par a meters f or  P F - 0 6 9 5 4 5 2 2 ................................................................ 2 1 
 ............................. 2 1 
 
LI S T O F FI G U R E S  
Fi g ur e 1.  
St u d y Desi g n Sc he matic: S e q ue ntial, Place b o -C o ntr olle d, 5 - Peri o d, 
Cr oss o ver Desi g n  .................................................................................... 7 
 
A P P E N DI C E S  
A p pe n di x 1. P K A nal yses  – E xa m ple of S A S C o de f or mi xe d effects m o del  ....................... 2 4 
A p pe n di x 2. Cate g orical Classes f or E C G a n d Vital Si g ns of P ote ntial Cli nical C o ncer n  ..... 2 5 
A p pe n di x 3. List of A b br e viati o ns  ....................................................................................... 2 6 
 
 
 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI
C CI


Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
PFIZER  CONFIDENTIAL  
TMF Doc ID: 98.03 
Page 5 of 27 
1. VERSION HISTORY 
Table 1. 
Summary of Changes  
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1 
14 Sept 2023 
Original  
17 July 2023 
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 C4001001. 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.  
Text in italics is taken directly from the protocol. 
2.1. Modifications to the Analysis Plan Described in the Protocol 
No modifications. 
2.2. Study Objectives, Endpoints, and Estimands 
Type 
Objective 
Endpoint 
Estimand 
Primary: 
Safety 
(Section 
3.1) 
To evaluate the safety and 
tolerability of single oral doses of 
PF-06954522, administered to 
healthy adult participants. 
Assessment of AEs, safety 
laboratory tests, vital signs (blood 
pressure, pulse rate, respiratory 
rate and temperature), cardiac 
telemetry and standard 12-lead 
ECGs, and PE. 
N/A 
Secondary: 
PK 
(Section 
3.2) 
To characterize plasma PK of PF-
06954522 following single oral 
doses of PF-06954522 
administered to healthy adult 
participants. 
PF-06954522 PK parameters: 
AUClast, Cmax, Tmax, and if data 
permit, AUCinf and t½. 
N/A 
Tertiary/Exploratory: 
PK 
(Section 
3.3.1) 
To further characterize plasma PK 
of PF-06954522 following single 
oral doses of PF-06954522 
administered to healthy adult 
participants. 
Additional PF-06954522 PK 
parameters: AUClast(dn), Cmax(dn), 
and if data permit, AUCinf(dn), 
CL/F, and Vz/F. 
N/A 
PK 
(Section 
3.3.2) 
Optional: to characterize the effect 
of food (high-fat breakfast) on the 
plasma PK of PF-06954522 
PF-06954522 PK parameters after 
a high-fat meal: AUClast, Cmax, Tmax 
N/A 
090177e19ea48cd2\Final\Final On: 20-Sep-2023 22:12 (GMT)


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 6 of 2 7  
f oll o wi n g si n gle or al d oses of P F-
0 6 9 5 4 5 2 2 i n  he alt hy a d ult 
p artici p a nts.  
a n d if d at a per mit, A U C i nf, C L/ F, 
V z/ F a n d t½ . 
N /A  
Saf et y a n d 
P K  
( Secti o n 
3. 3. 4 ) 
O pti o n al: t o ex pl ore t he s afety, 
t oler a bility, a n d pl as m a P K of P F -
0 6 9 5 4 5 2 2 i n he alt hy a d ult 
J a p a nese p artici p a nts. 
Assess me nt of A Es, s afety  
l a b or at ory tests, vit al si g ns ( bl o o d 
press ure, p ulse r ate a n d 
te m per at ure), st a n d ar d 1 2-le a d 
E C Gs a n d t he f oll o wi n g P F -
0 6 9 5 4 5 2 2 P K  p ar a meters i n 
J a p a nese p artici p a nts: A U C l ast, 
C m a x , Tm a x , a n d if d at a per mit, 
A U C i nf, C L/ F, Vz/ F a n d t½.  
N /A  
 
2. 3.  St u d y Desi g n  
T his st u dy is a r a n d o mize d d o u ble -bli n de d (i nvesti g at or - a n d p artici p a nt -bli n de d), s p o ns or -
o pe n,  first  i n  h u m a n  ( FI H),  si n gle -asce n di n g  or al  d ose,  5 -peri o d  cr oss ov er,  pl ace b o  
s u bstit uti o n desi g n i n 1 c o h ort of he alt hy a d ult p artici p a nts. A n a d diti o n al o pti o n al c o h ort, 
e nr olli n g he alt hy a d ult p artici p a nts i n u p t o 4 cr oss over peri o ds, m ay be i ncl u de d t o per mit 
assess me nt of a ny of t he f oll o wi n g: re pe at of a previ o usly a d mi nistere d d ose level; st u dyi n g 
a d diti o n al d ose levels as dict ate d by t he ev al u ate d s afet y, t oler a bility or P K of e arlier d ose 
levels; or a ny ot her assess me nt nee de d t o meet t he o bjectives of t his st u dy. A sec o n d o pti o n al 
c o h ort e nr olli n g J a p a nes e p artici p a nts t o re ceive P F - 0 6 9 5 4 5 2 2 or pl ace b o i n u p t o 3 peri o ds, 
m ay be i ncl u de d.  
A p pr oxi m ately 2 4 he alt hy a d ult p artici p a nts will be e nr olle d i n t he st u dy. T his i ncl u des u p t o 
a p pr oxi m ately 1 0 he alt hy p artici p a nts f or C o h ort 1, u p t o  a p pr oxi m ately 8 he alt hy p artici p a nts 
f or o pti o n al C o h ort 2 a n d u p t o a p pr oxi m ately 6 he alt hy J a p a nese p artici p a nts f or t he o pti o n al 
C o h ort 3. T he act u al n u m ber of J a p a nese p artici p a nts m ay be a dj uste d b ase d o n e mer gi n g 
d at a or o per ati o n al f act ors  wit h a m axi m u m s a m ple size  of u p t o 8 p artici p a nts ( 6 receivi n g 
P F -0 6 9 5 4 5 2 2 a n d 2 receivi n g pl ace b o i n e ac h peri o d). 
A s a m ple st u dy desi g n sc he m atic is prese nte d i n Fi g ure 1 . It s h o ul d be n ote d t h at t his is f or 
ill ustr ative p ur p oses, o nly.  
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI




Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
PFIZER  CONFIDENTIAL  
TMF Doc ID: 98.03 
Page 8 of 27 
3.1.1. Adverse Events 
An AE is considered a TEAE if the event started during the effective duration of treatment. All 
events that start on or after the first dose of study intervention, but before the end of the study 
will be flagged as TEAEs. The algorithm will not consider any events that started prior to the 
first dose date. 
Events that occur in a non-treatment period (eg, washout or follow-up) will be counted as 
treatment emergent and attributed to the most recent treatment taken. 
A 3-tier approach for summarizing AEs will not be used due to the low number of participants 
planned to be recruited.  
3.1.2. Clinical Safety Laboratory Data 
Safety laboratory tests will be performed as described in the protocol. 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition. 
Baseline will be the last pre-dose measurement in each study period.  
To determine if there are any clinically significant laboratory abnormalities, the hematological, 
clinical chemistry (serum) and urinalysis safety tests will be assessed against the criteria 
specified in the sponsor reporting standards. The assessment will take into account whether 
each participant’s baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter. 
3.1.3. Vital Signs 
Single supine blood pressure and pulse rate measurements will be taken at screening, follow-
up visit and at early termination (if applicable). Triplicate supine measurements will be taken 
at all other times as detailed in the Schedule of Activities (SoA) in the protocol. The average 
of the triplicate measurements will be calculated prior to analyzing the data. Respiratory rate 
and temperature will be measured at each timepoint specified in the protocol. 
Baseline for these measures will be defined as the average of the triplicates (if applicable) at 
last nominal pre-dose measurement time in each study period.  
The following endpoints will be determined: 
x Change from baseline (CFB) in systolic and diastolic BP, pulse rate, respiratory rate 
and temperature. 
x The minimum and maximum post-dose systolic and diastolic BP, pulse rate, respiratory 
rate and temperature. 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
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x The maximum increase and decrease from baseline over all measurements taken post-
dose for systolic and diastolic BP, pulse rate, respiratory rate and temperature values 
 
The maximum increase from baseline will be calculated by selecting the maximum change 
from baseline over the respective period, except in the case where a participant does not show 
an increase. In such an instance, the minimum decrease should be taken. Similarly, the 
maximum decrease from baseline will be determined by selecting the minimum value of the 
change from baseline. In cases where a participant does not show a decrease, the minimum 
increase should be taken. 
3.1.4. Continuous Cardiac Monitoring 
Continuous cardiac monitoring will be performed using telemetry as outlined in the protocol. 
All abnormal rhythms will be recorded and reviewed by the study physician for the presence 
of rhythms of potential clinical concern. The time, duration, and description of the clinically 
significant event will be recorded in the CRF. 
Events deemed of clinical concern will be recorded as AEs and will be summarized as part of 
the standard AE outputs. 
3.1.5. Electrocardiograms 
A single 12-lead ECG will be obtained on all participants at screening, follow-up visit and at 
early termination (if applicable). 12-lead ECGs will be recorded in triplicate at all other times 
as detailed in the SoA in the protocol. The average of the triplicate readings collected at each 
assessment time will be calculated for each ECG parameter. If one or two of the triplicates are 
missing, the non-missing values will be used for the average, and missing values will not be 
imputed. 
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 
GHVFULEHGLQDVDIHW\VHFWLRQRIWKH&65LQRUGHUWRSODFHWKH!ఇ 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 average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1H, 
-0.5H, and pre-dose 0H; total of 9 ECG measurements) collected before morning dose 
administration on Day 1 will serve as each participant’s baseline value in each study period.  
ECG endpoints include heart rate, QT interval, PR interval and QTcF and QRS complex. If 
not supplied QTcF will be derived using Fridericia’s heart rate correction formula [1]: 
 
 
QTcF (msec) = QT (msec) / (RR)1/3 where RR (sec) = 60/HR (if RR not provided). 
 
The following endpoints will be determined: 
x Change from baseline in QT, QTcF, PR, QRS interval and heart rate 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
PFIZER  CONFIDENTIAL  
TMF Doc ID: 98.03 
Page 10 of 27 
x The maximum post-dose QTcF, heart rate, PR and QRS interval 
x The maximum increase from baseline over all measurements taken post-dose for QTcF, 
heart rate, PR and QRS values  
 
The maximum increase from baseline will be calculated by selecting the maximum change 
from baseline over the respective period, except in the case where a participant does not show 
an increase.  In such an instance, the minimum decrease should be taken. 
3.1.6. Physical Examinations 
Complete physical examinations will be conducted at screening or upon admission for a 
participant’s first period in the study. At all other timepoints, a brief physical exam may be 
performed for the findings during a previous exam or new/open AEs at the investigators 
discretion. Height and weight will only be measured at the screening visit. 
Physical examination findings collected during the study will be considered source record and 
will not be required to be reported, unless otherwise noted.  
Any untoward physical examination findings that are identified during the active collection 
period will be captured as AEs or SAEs, if those findings meet the definition of an AE or SAE, 
and will be summarized as part of the standard AE outputs. 
3.2. Secondary Endpoint(s) 
Blood samples for PK analysis of PF-06954522 will be taken according to the SoA in the 
protocol. 
 
The plasma PK parameters for PF-06954522, following oral dose administration, will be 
derived from the plasma concentration-time profiles using standard noncompartmental 
methods as detailed in Table 2, as data permit. Table 2 shows the analysis scale and method 
for each parameter. 
In all cases, actual PK sampling times will be used in the derivation of PK parameters. If actual 
PK sampling times are not available, nominal PK sampling times will be used in the derivation 
of PK parameters. 
 
The following plasma PK parameters as described in Table 2 will be determined: 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
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Table 2. Summary of PF-06954522 plasma PK parameters to be calculated. 
Parameter 
Definition 
Method of 
Determination 
Analysis Scale 
Analysis 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 
ln 
A, D 
AUClast 
Area under the 
plasma concentration-
time profile from time 
0 to the time of the 
last quantifiable 
concentration (Clast) 
Linear/Log 
trapezoidal method 
ln 
A, D 
Cmax  
Maximum plasma 
concentration 
Observed directly 
from data 
ln 
A, D 
Tmax  
Time for Cmax 
Observed directly 
from data as time of 
first occurrence 
R 
D 
t½* 
Terminal elimination 
half-life 
Loge(2)/kel, where kel 
is the terminal phase 
rate constant 
calculated by a linear 
regression of the log-
linear concentration-
time curve. Only 
those data points 
judged to describe the 
terminal log-linear 
decline will be used 
in the regression. 
R 
D 
*=if data permits.  
Abbreviations: A=analyzed using a statistical model (if applicable); D=displayed with descriptive statistics as 
outlined in Table 5 in Section 6.2; ln=natural-log transformed; R = raw (untransformed). 
3.3. Other Endpoint(s) 
3.3.1. Additional Plasma PF-06954522 PK Parameters 
Additional plasma PF-06954522 PK parameters, as described in Table 3, will be determined: 
090177e19ea48cd2\Final\Final On: 20-Sep-2023 22:12 (GMT)


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 2 of 2 7 
T a ble 3. A d diti o n al P F - 0 6 9 5 4 5 2 2 Pl as m a P K P ar a meters  
P ar a m et er  
Defi niti o n  
Met h o d of 
Deter mi n ati o n  A n al ysis Sc ale  
A n al ysis Met h o d  
A U C i nf ( d n) * 
D ose -n or malize d 
A U C i nf 
A U C i nf/ D ose 
l n 
D  
A U C last ( d n) 
D ose -n or malize d 
A U C last 
A U C last/ D ose 
l n 
D  
C m a x  ( d n) 
D ose -n or malize d 
C m a x  
C m a x / D ose 
l n 
D  
C L/ F *  
A p par e nt clear a nce 
D ose/ A U C i nf 
l n 
D  
V z/ F*  
A p par e nt v ol u me of 
distri b uti o n  
D ose/( A U C i nf x 
k el) 
l n 
D  
* =if dat a per mits.  
A b bre viati o ns: D = dis pla ye d wit h descri pti ve st atisti cs as o utli ne d i n  T a bl e 6  i n Se cti o n  6. 3. 1 ; d n = n or maliz e d 
t o a 1 m g P F- 0 6 9 5 4 5 2 2 d ose; l n = nat ural-l o g tra nsf or m e d; R = ra w ( u ntra nsf or m e d). 
3. 3. 2.  Pl as m a P F - 0 6 9 5 4 5 2 2 P K P ar a meters D uri n g F o o d Effect P eri o d (if c o n d ucte d)  
If c o n d ucte d, the plas ma P F - 0 6 9 5 4 5 2 2 P K para meters descri be d i n T a ble 2  a n d T a ble 3  will 
als o be deter mi ne d d uri n g t he f e d peri o d.  
3. 3. 4.  S a f et y S u m m aries a n d P K P ar a meters D uri n g J a p a nese C o h ort (if c o n d ucte d)  
If c o n d ucte d, t he safet y s u m maries as descri be d i n Secti o n 3. 1  a n d t he P K para meters as 
descri be d i n Secti o ns 3. 2  a n d 3. 3. 1  will als o be deter mi ne d f or t he Ja pa nese c o h ort.  
3. 4.  B aseli ne V ari a bles  
N ot a p plica ble. 
3. 5.  S af et y E n d p oi nts  
See  Secti o n  3. 1  f or details. 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 3 of 2 7 
4.  A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S ) 
D ata f or all partici pa nts  will be assesse d t o deter mi ne if partici pa nts  meet t he criteria f or 
i ncl usi o n  i n  eac h  a nal ysis  p o p ulati o n  pri or  t o  u n bli n di n g  a n d  releasi n g  t he  data base  a n d 
classificati o ns will be d oc u me nte d  per sta n dar d o perati n g pr oce d ures.  
P o p ul ati o n  
Descri pti o n  
A p plic a b le A n al ysis (f or 
a d diti o n al i nf or m ati o n  
refer t o secti o n 6) 
E nr olle d  
“ E nr olle d ” me a ns a p artici p a nt’s, or t heir 
le g ally a ut h orize d re prese nt atives, 
a gree me nt t o p artici p ate i n a cli nic al st u dy 
f oll o wi n g c o m pleti o n of t he i nf or me d 
c o nse nt pr ocess a n d r a n d o miz ati o n t o st u dy 
i nterve nti o n.  
 
S afety A n alysis 
Set  
All p artici p a nt s r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o t ake at le ast 1 d ose of 
st u dy i nterve nti o n. P artici p a nts will be 
a n alyze d acc or di n g t o t he pr o d uct t hey 
act u ally receive d.  
Secti o n 6. 1  Pri mar y 
E n d p oi nt(s) , Secti o n 6. 3. 4  
Safet y S u m maries a n d P K 
Para meters D uri n g 
Ja pa nes e C o hort, 6. 5. 1  
Baseli ne S u m maries  
P K 
C o nce ntr ati o n 
Set  
All p artici p a nts r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o receive at le ast 1 d ose 
of st u dy i nterve nti o n a n d i n w h o m at le ast 1 
pl as m a / uri ne c o nce ntr ati o n v al ue is 
re p orte d. 
Secti o n 6. 2  Sec o n dar y 
E n d p oi nt(s), 6. 3. 4  Safet y 
S u m maries a n d P K 
Para meters D uri n g 
Ja pa nes e C o h ort 
P K P ar a meter 
Set  
All p artici p a nts r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o receive at le ast 1 d ose 
of st u dy i nterve nti o n a n d h ave at le ast 1 of 
t he P K p ar a meters of i nterest c alc ul ate d. 
Secti o n 6. 2  Sec o n dar y 
E n d p oi nt(s), Secti o n 6. 3. 1  
A d diti o nal Plas ma P F -
0 6 9 5 4 5 2 2 P K Para meters, 
Secti o n 6. 3. 2  Plas ma P F -
0 6 9 5 4 5 2 2 P K Para meters 
D uri n g F o o d Effect P eri o d, 
Secti o n 6. 3. 4  Safet y 
S u m maries a n d P K 
Para meters D uri n g 
Ja pa nes e C o h ort 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 4 of 2 7 
P o p ul ati o n  
Descri pti o n  
A p plic a b le A n al ysis (f or 
a d diti o n al i nf or m ati o n  
refer t o secti o n 6) 
 
5.  G E N E R A L M E T H O D O L O G Y  A N D C O N V E N TI O N S  
5. 1.  H y p ot heses  a n d Decisi o n R ules  
T her e is n o statistical h y p ot hesis testi n g pla n ne d f or t his st u d y, a n d n o statistical decisi o n r ules 
will be a p plie d.  
5. 2.  Ge ner al Met h o d s 
U nless ot her wise state d, all s u m maries a n d pl ots will be prese nte d b y d ose le vel, wit h data 
fr o m  diff er e nt  p o p ulati o ns  ( e. g.  n o n-Ja pa nese  a n d  Ja pa nese  partici pa nts),  if  a p pr o priate,  
r e p orte d se par atel y. E ac h dietar y all ocati o n (i. e., sta n dar d a n d hi g h fat brea kfast)  will als o be 
r e p orte d se par atel y. 
If a d ose le vel is r e peate d acr oss 2 or m ore c o h orts ( wit hi n a dietar y all ocati o n ), t he data will 
be c o m bi ne d.  
U nless ot her wise state d t he s u m mar y ta bles a n d/ or statistical a nal yses ma y o nl y i ncl u de a 
si n gle p o ole d place b o gr o u p acr oss all i ncl u de d c o h orts. Place b o will be p o ole d fr o m all d ose 
escalati o n peri o ds b ut n ot t he f e d peri o d  or t he Ja pa nese c o h ort.  
5. 2. 1.  A n al yses f or C o nti n u o us E n d p oi nts  
U nless ot her wise state d, c o nti n u o us varia bles will be prese nte d usi n g s u m mar y statistics:  
n u m ber of o bser vati o ns, arit h metic mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d ma xi m u m 
val ues.   
L o g tr a nsf or me d c o nti n u o us varia bles will be prese nte d usi n g s u m mar y statistics: n u m ber of 
o bser vati o ns,  arit h metic  mea n,  me dia n,  C V %,  sta n dar d  de viati o n,  mi ni m u m,  ma xi m u m,  
ge o metric mea n a n d ge o metric C V %. 
5. 2. 2.  A n al yses f or C at e g oric al E n d p oi nts  
Cate g orical varia bles will be pr ese nte d usi n g s u m mar y statistics: n u m ber of o bser vati o ns a n d 
per ce nta ges.   
5. 2. 3.  Mi xe d Eff ect s M o del  
A mi xe d eff ects m o del wit h tr eat me nt as a fi xe d effect a n d partici pa nt as a ra n d o m effect will 
be use d . 
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
C CI


Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 5 of 2 7 
Esti mates of t he a dj uste d (least s q uares) mea n differe nces ( T est - Refere nc e) a n d c orres p o n di n g 
9 0 % c o nfi de nce i nter vals will be o btai ne d fr o m t he m o del. T he a dj uste d mea n  differe nces a n d 
9 0 % c o nfi de nce i nter vals f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates of t he 
r ati o of a dj uste d ge o metric mea ns ( T est/ Refere nce) a n d 9 0 % c o nfi de nce i nter vals f or t he rati os. 
T he mi xe d eff ects m o del will be i m ple me nte d usi n g S A S Pr oc Mi xe d, wit h R E M L esti mati o n 
met h o d a n d t he Ke n war d-R o ger de grees of free d o m al g orit h m .  
 
Resi d uals fr o m t he m o dels will be e xa mi ne d f or n or malit y a n d t he prese nce of o utliers via 
vis ual i ns pecti o n of pl ots of r esi d uals vs pre dicte d val ues a n d n or mal pr o ba bilit y pl ots of 
r esi d uals, b ut t hese will n ot be i ncl u de d i n t he cli nical st u d y re p ort. If t here are maj or de viati o ns 
fr o m n or malit y or o utliers ( w her e st u de ntize d [c o n diti o nal] resi d uals are greater t ha n 3 or less 
t ha n -3), t he n t he eff ect of t hese o n t he c o ncl usi o ns ma y be i n vesti gate d t hr o u g h alter nati ve 
tr a nsf or mati o ns a n d/ or a nal yses e xcl u di n g o utliers. J ustificati o n f or a n y alter nati ve t o t he 
pla n ne d a nal ysis will be gi ve n i n t he re p ort of t he st u d y if a p plica ble.  
E xa m ple c o de is s h o w n i n  A p pe n di x 1 . 
5. 3.  Met h o ds t o M a n a ge Missi n g D at a  
F or t he a nal ysis of saf et y e n d p oi nts, t he s p o ns or data sta n dar d r ules f or i m p utati o n will be 
a p plie d.   
5. 3. 1.  C o nce nt r ati o ns Bel o w t he Li mit of Q u a ntific ati o n  
I n all P K data pr ese ntati o ns ( e xce pt listi n gs), c o nce ntrati o ns bel o w t he li mit of q ua ntificati o n 
( B L Q) will be set t o zer o. I n listi n gs B L Q val ues will be re p orte d as “ < L L O Q”, w here L L O Q 
will be r e place d wit h t he val ue f or t he L L O Q.   
I n all e x pl or at or y bi o mar ker (
) data prese ntati o ns (e xce pt listi n gs), c o nce ntrati o ns 
bel o w t he li mit of q ua ntificati o n ( B L Q) will be set t o t he l o wer li mit of q ua ntificati o n ( L L O Q).  
5. 3. 2.  De vi ati o ns, Missi n g C o nce ntr ati o ns a n d A n o m al o us V al ues  
I n P K a n d e x pl or at or y bi o mar ker s u m mar y ta bles a nd pl ots of me dia n pr ofiles, statistics will 
be calc ulate d ha vi n g set c o nce ntr ati o ns t o missi n g if o ne of t he f oll o wi n g cases is tr ue:   
1.  A c o nce ntr ati o n has bee n c ollecte d as N D (ie, n ot d o ne) or N S (ie, n o sa m ple),   
2.  A de viati o n i n sa m pli n g ti me is of s ufficie nt c o ncer n or a c o nce ntrati o n has bee n 
fla g ge d a n o mal o us b y t he p har mac o ki neticist/statisticia n.  
N ote t hat s u m mar y statistics will n ot be prese nte d at a partic ular ti me p oi nt if m ore t ha n 5 0 % 
of t he data ar e missi n g.  
Partici pa nts w h o e x perie nce e ve nts t hat ma y affect t heir P K pr ofile (e. g., lac k of c o m plia nce 
wit h d osi n g or v o miti n g) ma y be e xcl u de d fr o m t he P K a nal ysis. At t he discreti o n of t he 
p har mac o ki neticist, a c o nce ntr ati o n val ue ma y als o be e xcl u de d if t he de viati o n i n sa m pli n g 
ti me is of sufficie nt c o ncer n or if t he c o nce ntrati o n is a n o mal o us f or a n y ot her reas o n.  
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
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A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure. 
5.3.3. Plasma Pharmacokinetic Parameters 
Actual PK sampling times will be used in the derivation of plasma PK parameters. 
If a PK parameter cannot be derived from a participant’s concentration data, the parameter will 
be coded as NC (i.e., not calculated). (Note that NC values will not be generated beyond the 
day that a participant discontinues.) 
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
ZLOOEHSUHVHQWHGIRUDSDUWLFXODUWUHDWPHQWJURXSDQDO\WHZLWKHYDOXDEOHPHDVXUHPHQWV)RU
statistical analyses (i.e., mixed effects model), PK parameters coded as NC will also be set to 
missing; and analyses will not be performed for a particular parameter if more than 50% of the 
data are NC. 
If an individual participant has a known biased estimate of a plasma PK parameter (due, for 
example, to an unexpected event such as vomiting before all the compound is adequately 
absorbed in the body), this will be footnoted in summary tables and may not be included in the 
calculation of summary statistics or statistical analyses. 
6. ANALYSES AND SUMMARIES 
For all presentations, study day will refer to the day within a particular treatment period, unless 
otherwise specified. 
NOTE: For all analyses presented below ‘by treatment’ refers to by dose, population (if 
applicable) and dietary allocation (if applicable), as described in Section 5.2,  unless 
otherwise stated. Overall by population refers to reporting Japanese and Non-Japanese 
populations separately (i.e. Cohort 1 and Cohort 2 together, and Cohort 3 separately). 
6.1. Primary Endpoint(s) 
6.1.1. Adverse Events  
AEs will be listed and summarized by treatment and overall by population and in accordance 
with sponsor reporting standards using the safety population defined in Section 4.   
Incidence and severity of TEAE tables will additionally be produced (‘All causality’ and 
‘Treatment related,’ separately) to summarize the total number of adverse events by preferred 
term, which will be reported by treatment and overall by population, in accordance with 
sponsor reporting standards using the safety analysis set defined in Section 4.   
The AEs will be presented sorted in descending frequency based on the overall number of AEs 
(by preferred term or system order class as appropriate) across doses. 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
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6.1.2. Clinical Safety Laboratory Data   
Safety laboratory data will be listed and summarized by treatment and overall by population, 
in accordance with the sponsor reporting standards using the safety analysis set defined in 
Section 4. Baseline is as defined in Section 3.1.2. 
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. 
In summary and listing tables, laboratory abnormalities occurring pre-dose on Day -1 for each 
period starting with Period 2 (or a participant’s individual second dosing Period, for any 
participant that starts the study after Period 1), will be attributed to the dose from the previous 
period (e.g., for Cohort 1, an occurrence pre-dose at Period 2 Day -1 will be attributed to the 
Period 1 dose). Any abnormality pre-dose in Period 1 or pre-dose at a participant’s first dosing 
period would be reported as that participant’s baseline measure for the period. Unplanned 
assessments will be included in summary abnormality tables and listings. 
6.1.3. Vital Signs  
Absolute values and changes from baseline (as defined in Section 3.1.3) in supine systolic and 
diastolic blood pressure, respiratory rate, temperature, and pulse rate will be listed, and 
summarized by treatment and timepoint, according to sponsor reporting standards using the 
safety population defined in Section 4. 
Mean absolute values and mean changes from baseline for systolic and diastolic blood 
pressure, respiratory rate, temperature, and pulse rate will be plotted against time point. On 
each plot, there will be 1 line for each treatment with all doses on the same plot. Corresponding 
individual plots of changes from baseline will also be produced for each treatment. 
Maximum and minimum absolute values and changes from baseline (as defined in Section 3.1) 
for supine vital signs will also be summarized descriptively by treatment using categories as 
defined in Appendix 2.  
Numbers and percentages of participants meeting the categorical criteria will be provided. All 
planned and unplanned post dose time points will be counted in these categorical summaries. 
All values meeting the criteria of potential clinical concern will be listed.  
Values meeting the categorical criteria occurring pre-dose on Day 1 for each period starting 
with Period 2, will be attributed to the dose from the previous period (e.g., for cohort 1, an 
occurrence pre-dose at Period 2 Day 1 will be attributed to the Period 1 dose). For any 
participant who starts the study after Period 1, the same considerations as described in Section 
6.1.2 apply. 
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. Unplanned 
assessment will be listed but will be excluded from safety summary except for categorical 
summaries. 
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6.1.4. Continuous Cardiac Monitoring 
Continuous cardiac monitoring will be performed using telemetry as outlined in the protocol. 
Data will be reviewed and summarized on an ongoing basis during the study to evaluate the 
safety of participants. 
All abnormal rhythms will be recorded and reviewed by the investigator for the presence of 
rhythms of potential clinical concern.  The time, duration, and description of the clinically 
significant event will be recorded in the CRF.  Events deemed of clinical concern will be 
recorded as AEs and will be summarized as part of the standard AE outputs. 
6.1.5. Electrocardiograms 
Absolute values and changes from baseline in QT, heart rate, QTcF, PR and QRS will be 
summarized by treatment and timepoint using sponsor reporting standards, using the safety 
analysis set defined in Section 4. Baseline is as defined in Section 3.1.5. 
Mean changes from baseline in QT, heart rate and QTcF will be plotted against time post-dose. 
On each plot there will be one line for each treatment. Corresponding individual plots of 
changes from baseline will also be produced for each treatment. 
Changes from baseline in QTcF will also be plotted separately against drug concentrations of 
PF-06954522. 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. 
Maximum increase from baseline for QTcF, heart rate, PR and QRS values will be summarized 
by treatment according to sponsor reporting standards.  
ECG endpoints and changes from baseline (QTcF [1], PR and QRS) will also be summarized 
descriptively by treatment (if applicable) using categories as defined in Appendix 2 . Numbers 
and percentages of participants meeting the categorical criteria will be provided. All planned 
and unplanned postdose time points will be counted in these categorical summaries.   
Values meeting the categorical criteria occurring pre-dose on Day 1 for each period starting 
with Period 2, will be attributed to the treatment from the previous period (e.g., for cohort 1, 
an occurrence pre-dose at Period 2 Day 1 will be attributed to the Period 1 dose). For any 
participant who starts the study after Period 1, the same considerations as described in Section 
6.1.2 apply. 
Listings of participants with any single post-dose value >500msec will also be produced for 
QTcF. 
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. Unplanned 
assessment will be listed but will be excluded from safety summary except for categorical 
summaries. 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
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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. The results of such analyses may not be included in the CSR. 
6.1.6. Physical Examinations 
Physical examinations will be performed as described in the protocol.   
Medical history and physical examination 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, and will be summarized as part of the standard AE outputs. 
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted.  
6.2. Secondary Endpoint(s) 
Plasma PK parameters for PF-06954522, as described in Section 3.2, will be listed and 
summarized descriptively by treatment and day, as applicable, for participants in the PK 
Parameter Set (as defined in Section 4). Missing values will be handled as detailed in Section 
5.3.  
Each PK parameter will be summarized by treatment and day (as appropriate) using the 
summary statistics as specified in the table below: 
Table 5. Summary Statistics for PF-06954522 Plasma PK Parameters  
Parameter 
Summary Statistics 
AUClast, AUCinf*, and Cmax  
N, arithmetic mean, median, CV%, standard deviation, 
minimum, maximum, geometric mean and geometric 
CV%. 
Tmax 
N, median, minimum, maximum.  
t½.* 
N, arithmetic mean, CV%, standard deviation, median, 
minimum, maximum.  
*: if data permit 
Supporting data from the estimation of AUCinf and t1/2 will be listed by dose: terminal phase 
rate constant (kel); goodness of fit statistic from the log-linear regression (r2); the percent of 
AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of time points used 
in the estimation of kel. This data may be included in the clinical study report. 
The following plots will be presented using the PK Parameter Set (as defined in Section 4): 
 Box and whisker plots for dose-normalized PK parameters [AUCinf (dn), AUClast (dn) 
and Cmax(dn)] will be presented in logarithmic scale by treatment and overlaid with 
observed values of individual participants and geometric means. Geometric means will 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
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have a different symbol than the individual values. Individual values from different 
cohorts will also have a different symbol. A footnote will be added to the plots to 
indicate that geometric means are presented and that data from all cohorts are presented 
on the plot. 
The following will additionally be presented for the plasma concentration data using the PK 
Concentration Set (as defined in Section 4):  
- 
a listing of all concentrations sorted by participant ID and nominal time post-dose for 
each treatment separately. The concentration listing will also include the actual times. 
Deviations from the nominal time will be given in a separate listing.  
- 
a summary of concentrations by each nominal time post-dose (produced separately for 
each treatment), where the set of statistics will include n, mean, median, standard 
deviation, coefficient of variation (CV), minimum, maximum and the number of 
concentrations above the lower limit of quantification.  
- 
mean and median concentration time plots (on both linear and semi-log scales) against 
nominal time post-dose by treatment. One plot for each scale will be presented, which 
will include all doses in the same plot coloured by treatment. 
- 
individual concentration time plots by treatment (on both linear and semi-log scales) 
against actual time post-dose (there will be separate spaghetti plots for each treatment, 
with a line for each participant per scale). 
- 
individual concentration time plots by participant (on both linear and semi-log scales) 
against actual time post-dose.  
The scale used for the x-axis (time) of these plots will be decided on review of the data, and 
will depend on how long PF-06954522 concentration is quantifiable in the matrix. 
The nominal PK sampling time will be used for summary statistics and relevant median plots, 
whereas for individual participant plots by time, the actual PK sampling time will be used. 
6.3. Other Endpoint(s) 
6.3.1. Additional Plasma PF-06954522 PK Parameters 
Additional plasma PK parameters for PF-06954522, as described in Section 3.3.1, will be listed 
and summarized descriptively, by treatment and day, as applicable, as described in Table 6 for 
participants in the PK Parameter Set (as defined in Section 4).  
Missing values will be handled as detailed in Section 5.3.  
Each PK parameter will be summarized by treatment as applicable as required in the table 
below: 
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Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 2 of 2 7 
6. 3. 4.  S af et y S u m m aries a n d P K  P ar a meters D uri n g J a p a nese C o h ort (if c o n d ucte d)  
If c o n d ucte d, P K par a meters as descri be d i n Secti o ns 3. 2  a n d 3. 3. 1  a n d safet y s u m maries as 
descri be d i n Secti o n 3. 1  will be r e p orte d se paratel y f or t his c o h ort. 
6. 3. 5.  B a n ke d Bi os peci m e ns  
Ba n ke d bi os peci me ns will be c ollecte d a n d retai ne d f or f ut ure a nal yses b ut will n ot be a nal yse d 
s pecificall y f or t his st u d y a n d will n ot be i ncl u de d i n t he C S R. 
6. 4.  S u bset A n al yses  
N o s u bset a nal yses will be perf or me d.  
6. 5.  B aseli ne a n d Ot her  S u m m aries a n d A n al yses  
6. 5. 1.  B aseli ne S u m m aries  
De m o gr a p hics data ( a ge, bi ol o gical se x, race, et h nicit y, b o d y wei g ht, b o d y mass i n de x a n d 
hei g ht) will be s u m marize d acr oss all partici pa nts i n t he safet y p o p ulati o n (as defi ne d i n  
Secti o n 4 ), b y c o h ort a n d o ver all b y p o p ulati o n  as descri be d i n  Secti o n  5. 2. 1  or Secti o n  5. 2. 2   
( as a p pr o priate). 
6. 5. 2.  St u d y C o n d uct a n d P artici p a nt  Dis p ositi o n  
Partici pa nt e val uati o n gr o u ps will s h o w e n d of st u d y partici pa nt dis p ositi o n b y treat me nt a n d 
o ver all b y p o p ulati o n a n d will s h o w w hic h partici pa nts were a nal yze d f or P K, bi o mar kers  a n d 
saf et y, w hic h ma y n ot be pr o d uce d i n o ne ta ble. Fre q ue nc y c o u nts a n d perce nta ges will be 
s u p plie d f or partici pa nt disc o nti n uati o n(s) b y treat me nt.   
6. 5. 3.  St u d y Tre at m e nt E x p os ure 
N ot a p plica ble.  
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6.5.4. Concomitant Medications and Nondrug Treatments 
All prior and concomitant medication(s) as well as non-drug treatment(s) will be provided in 
listings.   
6.6. Safety Summaries and Analyses 
See Section 6.1. 
7. INTERIM ANALYSES 
7.1. Introduction 
No formal interim analysis will be conducted for this study. 
7.2. Interim Analyses and Summaries 
Not applicable. 
8. REFERENCES 
1. FDA. Guidance for Industry E14 Clinical Evaluation of QT/QTc Interval Prolongation and 
Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Updated 24-AUG-2018. Accessed 
29-AUG-2023. https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/e14-clinical-evaluation-qtqtc-interval-prolongation-and-proarrhythmic-potential-
non-antiarrhythmic-0 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
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APPENDICES 
Appendix 1. PK Analyses – Example of SAS Code for mixed effects model 
An example of the PROC MIXED code:  
 
proc mixed data=tab.pk;   
 
class trt subject;   
 
model &var = trt / residual ddfm=KR;   
 
random subject /subject=subject;   
 
lsmeans trt/ diff cl alpha=0.1;   
run; 
 
 
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Protocol C4001001 (PF-06954522) Statistical Analysis Plan 
 
 
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Appendix 2. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern 
Categories for QTcF  
 
Absolute value of QTcF 
(msec)  
!450 and d480  
>480 and d500  
>500  
Increase from baseline in 
QTcF (msec)  
!30 and d60  
>60  
  
  
Categories for PR and QRS  
 
PR (msec)  
PD[300  
  
PR (msec) increase 
from baseline  
Baseline >200 and 
PD[LQFUHDVH  
%DVHOLQHDQG
PD[LQFUHDVH  
QRS (msec)  
PD[  
  
QRS (msec) increase 
from baseline  
ш50% increase  
  
  
Categories for Vital Signs  
 
Systolic BP (mmHg)  
min. <90  
  
Systolic BP (mmHg) change from baseline  
PD[GHFUHDVH  
PD[LQFUHDVH  
Diastolic BP (mmHg)  
min. <50  
  
Diastolic BP (mmHg) change from baseline  
PD[GHFUHDVH  
PD[LQFUHDVH  
Supine pulse rate (bpm)  
min. <40  
max. >120  
  
Measurements that fulfill these criteria are to be listed in the report.  
 
 
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Pr ot oc ol C 4 0 0 1 0 0 1 ( P F - 0 6 9 5 4 5 2 2) St atisti cal A nal ysis Pl a n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atisti c al A n al ysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 6 of 2 7 
A p pe n di x  3.  List o f A b bre vi ati o ns 
A b bre vi ati o n  
Ter m  
A E  
A d verse E ve nt  
A N O V A  
A nal ysis of varia nce  
A U C  
Ar ea U n der t he C ur ve  
A U C i nf  
Ar ea U n der t he C o nce ntrati o n-Ti me C ur ve fr o m ti me zer o 
e xtr a p olate d t o i nfi nit y 
A U C i nf ( d n) 
D ose N or malize d A rea U n der t he C o nce ntrati o n-Ti me C ur ve fr o m 
ti me zer o e xtra p olate d t o i nfi nit y 
A U C last  
Ar ea U n der t he C o nce ntrati o n-Ti me C ur ve fr o m ti me zer o t o t he last 
meas ur a ble c o nce ntrati o n  
A U C last ( d n) 
D ose N or malize d A rea U n der t he C o nce ntrati o n-Ti me C ur ve fr o m 
ti me zer o t o t he last meas ura ble c o nce ntrati o n 
B L Q  
Be l o w t he Li mit of Q ua ntitati o n 
B P  
Bl o o d Pr ess ure  
C F B  
C ha n ge fr o m Baseli ne  
C L  
Clear a nce  
C L/ F  
A p par e nt T otal B o d y C leara nce 
C m a x   
Ma xi m u m O bser ve d C o nce ntrati o n  
C m a x ( d n) 
D ose N or malize d M a xi m u m O bser ve d C o nce ntrati o n  
C R F  
Case R e p ort F or m  
C S R  
Cli nical St u d y Re p ort  
C V  
C oefficie nt of Variati o n  
D E R  
D ose Escalati o n Re vie w  
E C G  
Electr ocar di o gra m  
FI H  
First i n H u ma n  
H  
H o ur  
H R  
Heart r ate  
I D 
I de ntificati o n 
L L O Q  
L o wer Li mit of Q ua ntitati o n  
l n 
Nat ur al l o g  
m g  
M illi gr a m 
m m H g  
Milli meter of merc ur y  
msec  
Millisec o n d  
N  
N u m ber of partici pa nts  
N/ A  
N ot A p plica ble  
N C  
N ot Calc ulate d  
N D  
N ot D o ne  
N S  
N o Sa m ple  
P D  
P har mac o d y na mic  
P E  
P h ysical E xa mi nati o n  
0 9 0 1 7 7 e 1 9 e a 4 8 c d 2\ Fi n al\ Fi n al O n: 2 0- S e p- 2 0 2 3 2 2: 1 2 ( G M T)
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Abbreviation 
Term 
PK 
Pharmacokinetic(s) 
QTcF 
corrected QT (Fridericia method) 
REML 
Restricted Maximum Likelihood 
SAP 
Statistical Analysis Plan 
sec 
Second 
SoA 
Schedule of Activities 
TBD 
To Be Determined 
TEAE 
Treatment Emergent Adverse Event 
Tmax  
Time to maximum observed concentration 
t½  
Half life 
Vz/F  
Apparent volume of distribution 
 
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